黑猩猩腺病毒疫苗載運體的製作方法

2023-12-10 04:23:06

專利名稱：黑猩猩腺病毒疫苗載運體的製作方法
技術領域：
本發明涉及重組載體領域，更具體地涉及重組複製缺陷性黑猩猩腺病毒載體的產生和用途，來在哺乳動物宿主中引發免疫反應。
背景技術：
腺病毒(Ads)包含在兩棲動物、禽類和哺乳動物中發現的、具有無包被的二十面體衣殼結構的雙鏈DNA病毒的大家族(Straus，Adenovirus infections in humans.In The Adenoviruses.451-498，1984；Hierholzer et al.，J.Infect.Dis.，158804-813，1988；Schnurr andDondero，Intervirology.，3679-83，1993；Jong et al.，J Clin Microbiol.，373940-39451999)。與逆轉錄病毒相比，腺病毒可以轉導幾個哺乳動物物種的許多細胞類型，包括分裂和非分裂細胞，而不整合到宿主細胞的基因組中。
一般而言，腺病毒DNA一般是非常穩定的並保持游離(例如，染色體外)，除非發生了轉化或腫瘤發生。此外，在容易進行臨床級組合物的製藥規模生產的良好定義的生產系統中，腺病毒載體可以繁殖到高產量。這些特徵和它們被良好表徵的分子遺傳學，使得重組腺病毒載體成為用作疫苗載運體(carrier)的好的候選者。一般地，重組腺病毒載體的生產依靠使用能夠補足腺病毒基因產物的功能的包裝細胞系，所述功能已經被刪除或被工程化為無功能的。
目前，兩種良好表徵的人類C亞群腺病毒血清型(即，hAd2和hAd5)被廣泛地用作大多數用於基因治療的腺病毒載體的病毒主幹的來源。也已經測試了複製缺陷性人類腺病毒載體作為用於遞送各種免疫原的疫苗載體，所述免疫原來源於各種傳染原(例如，病毒、寄生蟲或細菌性病原體)和腫瘤細胞，包括腫瘤相關抗原(TAA)。在實驗動物(例如，齧齒動物、犬和非人靈長類)中進行的研究表明，攜帶轉基因的重組複製缺陷性人類腺病毒載體引發了針對轉基因產物的體液和細胞介導的免疫反應，所述轉基因編碼來源於人類乳頭狀瘤病毒(HPV-16)的E6和E7癌蛋白(He，Z et al.，(2001)Virology，2703583-3590)、狂犬病病毒糖蛋白(Xiang，Z.et al(1996)Virolgy，219220-227)、Plasmodium falciparum的環子孢子蛋白Rodriguez E.etal.(1997)J.Immunol.1581268-1274)以及其他異源抗原的免疫原。一般而言，研究人員已經報導了，通過使用利用預計可引發免疫反應的高劑量重組腺病毒載體的免疫方案；或通過使用採用腺病毒載體的連續施用的免疫方案，所述腺病毒載體來源於不同血清型但攜帶相同的轉基因產物用作強化免疫，在非人類實驗系統中成功地使用人類腺病毒載體作為疫苗載運體(Mastrangeli，et al.，Human Gene Therapy，779-87(1996)。
然而，預計的是，來源於遍在的人類血清型，例如2和5型的疫苗載運體將在人類群體中遇到先存的(pre-existing)體液和細胞免疫。因而，儘管已經在採用齧齒動物、犬和非人靈長類宿主的實驗系統中成功地使用複製缺陷性重組人類腺病毒作為疫苗載運體，預計人類的先天和適應性免疫會顯著地限制這些血清型作為疫苗載運體的實用性。這種預期是基於這一事實，包括2型和5型的C亞群腺病毒感染在人類群體中是地方性的。結果，作為自然感染的結果，大多數人類在生命的頭五年內血清轉變。因而，來源於在人類中天然感染並複製的病毒的載體，可能不是用作疫苗載運體的最優候選者。
與使用人類腺病毒衍生載體相關的另一個問題是，用於繁殖重組病毒的生產方法產生被有複製能力的腺病毒(RCA)汙染的載體成品的風險。這是起因於，來自重組載體和存在於E1補足輔助細胞系，例如人類293(Graham，F.L.et al，(1977)J.Gen.Virol.3659-72.)細胞中的腺病毒基因的重疊序列之間的同源重組。在為用於臨床試驗製備的載體成品中RCA的存在構成了安全風險，因為它可能促進複製缺陷性病毒的流動和傳播。缺陷病毒的傳播可能加重宿主免疫應答，並引起其他有害的免疫病理後果。(Fallux，F.J.，et al.HumanGene Therapy 91909-1917(1998)。因此，食品和藥品管理局(FDA)和其他管理機構已經頒布了指導原則，其建立了對可能存在於用於臨床用途的載體製品中的RCA水平的限制。加以RCA限制的意圖是確保患者有限地暴露於用於臨床試驗的組合物中的複製性腺病毒。
因而，存在著開發適用於哺乳動物宿主的腺病毒疫苗載運體的持續的需求，其是易於操作、可經受製藥規模的生產和長期儲存、在人類補足細胞系中能以高水平複製、高度的免疫原性、沒有與人類腺病毒的常見血清型交叉反應的中和B細胞表位、符合管理機構頒布的安全RCA標準、並且其符合在適合人類使用的激發/強化(prime/boost)方案中使用。
發明概述本發明涉及來源於黑猩猩腺病毒的重組複製缺陷性腺病毒載體和用於在人類E1表達細胞系中產生黑猩猩腺病毒載體的方法。本發明還提供了產生適用於人類的臨床級載體成品的方法，和使用所公開的載體作為疫苗載運體來引發保護性和/或治療性免疫反應的方法。本發明進一步提供了使用本發明的重組腺病毒來製備疫苗組合物的方法，所述疫苗組合物被設計以遞送編碼免疫原的轉基因和指導編碼免疫原的轉基因的表達。在一個實施方式中，本發明考慮使用所公開載體作為疫苗載運體用於疫苗的施用，所述疫苗包含編碼來源於傳染原的免疫原的轉基因。在第二種實施方式中，本發明考慮使用所公開的載體來製備和施用癌症疫苗。在特定的實施方式中，本發明考慮製備和施用包含編碼TAA的轉基因的癌症疫苗。
在一個方面，本發明公開了五種黑猩猩腺病毒(ChAds)的完整基因組序列，在此稱為ChAd3(SEQ ID NO1)(附圖5A-5K)、ChAd6(SEQ ID NO2)(附圖6A-6K)、CV32(SEQ ID NO3)(附圖7A-7K)、CV33(SEQ ID NO4)(附圖8A-8K)和CV23(SEQ ID NO5)(附圖9A-9J)。
ChAd3和ChAd6是根據在此公開的方法分離的新的腺病毒。ChAd3和ChAd6的基因組長度分別是37741和36648個鹼基對。ChAd3六鄰體基因(SEQ ID NO41)包含SEQ ID NO1的核苷酸(nt)19086-21965(不包括終止密碼子)，ChAd3纖維基因(SEQ IDNO42)包含SEQ ID NO1的nt 32805-34487(不包括終止密碼子)。ChAd6六鄰體(hexon)基因包含SEQ ID NO2的nt 18266-21124(SEQID NO43)(不包括終止密碼子)，它的纖維基因(SEQ ID NO44)包含SEQ ID NO2的nt 32218-33552(不包括終止密碼子)。根據從全長六鄰體肽的多重序列比對得出的序列同源性，ChAd3被分類入人類C亞群，ChAd6被分類入人類E亞群。
CV32、CV33和CV23腺病毒的基因組的長度分別是36,606、36,535和32,020個鹼基對。CV32(Pan 6)(ATCC N.VR-592)、CV33(Pan7)(ATCC N.VR-593)和CV23(Pan 5)(Esoterix Inc.，)全都被確定為與人類Ad4(hAd4)(E亞群)相關(Wigand，R et al.Intervirilogy1989，301-9)。然而，根據六鄰體序列比對，隨後將CV32表徵為與類似於hAd4相比更接近地類似於人類D亞群成員。
在第二個方面，本發明提供了根據在此公開的方法分離的21種其他黑猩猩腺病毒(ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82)的纖維基因和六鄰體基因的核苷酸序列。
ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19的纖維基因核苷酸序列分別在附

圖10-19中列出，在此稱為SEQ ID NO6-15(SEQ ID NO6，ChAd20)；(SEQ ID NO7，ChAd4)；(SEQ ID NO8，ChAd5)；(SEQ ID NO9，ChAd7)；(SEQ ID NO10，ChAd9)；(SEQ ID NO11，ChAd10)；(SEQ ID NO12，ChAd11)；(SEQ ID NO13，ChAd16)(SEQ IDNO14，ChAd17)和(SEQ ID NO15，ChAd19)ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的纖維基因核苷酸序列在此稱為(SEQ ID NO58，ChAd8)、(SEQ ID NO60，ChAd22)、(SEQID NO62，ChAd24)、(SEQ ID NO64，ChAd26)、(SEQ ID NO66，ChAd30)、(SEQ ID NO68，ChAd31)、(SEQ ID NO70，ChAd37)、(SEQ ID NO72，ChAd38)、(SEQ BD NO74，ChAd44)、(SEQ ID NO76，ChAd63)和(SEQ ID NO78，ChAd82)，並在序列表中列出。
ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19的六鄰體基因核苷酸序列分別在附圖21-30中列出，在此稱為SEQ ID NO16-25(SEQ ID NO16，ChAd20)；(SEQ ID NO17，ChAd4)；(SEQ ID NO18，ChAd5)；(SEQ ID NO19，ChAd7)；(SEQ ID NO20，ChAd9)；(SEQ IDNO21，ChAd10)；(SEQ ID NO22，ChAd11)；(SEQ ID NO23，ChAd16)；(SEQ ID NO24，ChAd17)和(SEQ ID NO25，ChAd19)。
ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的六鄰體基因核苷酸序列在此稱為(SEQ ID NO97，ChAd8)、(SEQ ID NO99，ChAd22)、(SEQ ID NO101，ChAd24)、(SEQ ID NO103，ChAd26)、(SEQID NO105，ChAd30)、(SEQ ID NO107，ChAd31)、(SEQ ID NO109，ChAd37)、(SEQ ID NO111，ChAd38)、(SEQ ID NO113，ChAd44)、(SEQ ID NO115，ChAd63)和(SEQ ID NO117，ChAd82)，並在序列表中列出。
在第三個方面，本發明提供了根據在此公開的方法分離的21種其他黑猩猩腺病毒(ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82)的纖維蛋白和六鄰體蛋白的胺基酸序列。
在此公開和要求權利的纖維蛋白稱為(SEQ ID NO83，ChAd3)、(SEQ ID NO84，ChAd6)、(SEQ ID NO48，ChAd20)、(SEQ ID NO49，ChAd4)、(SEQ ID NO50，ChAd5)、(SEQ IDNO51，ChAd7)、(SEQ ID NO52，ChAd9)、(SEQ ID NO53，ChAd10)、(SEQ ID NO54，ChAd11)、(SEQ ID NO55，ChAd16)、(SEQ ID NO56，ChAd17)、(SEQ ID NO57，ChAd19)、(SEQ IDNO59，ChAd8)、(SEQ ID NO61，ChAd22)、(SEQ ID NO63，ChAd24)、(SEQ ID NO65，ChAd26)、(SEQ ID NO67，ChAd30)、(SEQ ID NO69，ChAd31)、(SEQID NO71，ChAd37)、(SEQ IDNO73，ChAd38)、(SEQ ID NO75，ChAd44)、(SEQ ID NO77，ChAd63)和(SEQ ID NO79，ChAd82)。附圖20A-20G提供了比較在此公開和要求權利的纖維蛋白的胺基酸序列與以下纖維蛋白的胺基酸序列的比對C1(SEQ ID NO85)、CV68(SEQ ID NO86)、Pan5(作為選擇稱為CV23)(SEQ ID NO80)、Pan6(作為選擇稱為CV32)(SEQ ID NO81)和Pan7(作為選擇稱為CV33)(SEQ IDNO82)。
在此公開和要求權利的六鄰體蛋白稱為(SEQ ID NO122，ChAd3)、(SEQ ID NO123，ChAd6)、(SEQ ID NO87，ChAd20)、(SEQ ID NO88，ChAd4)、(SEQ ID NO89，ChAd5)、(SEQ IDNO90，ChAd7)、(SEQ ID NO91，ChAd9)、(SEQ ID NO92，ChAd10)、(SEQ ID NO93，ChAd11)、(SEQ ID NO94，ChAd16)、(SEQ ID NO95，ChAd17)、(SEQ ID NO96，ChAd19)、(SEQ IDNO98，ChAd8)、(SEQ ID NO100，ChAd22)、(SEQ ID NO102，ChAd24)、(SEQ ID NO104，ChAd26)、(SEQ ID NO106，ChAd30)、(SEQ ID NO108，ChAd31)、(SEQ ID NO110，ChAd37)、(SEQ ID NO112，ChAd38)、(SEQ ID NO114，ChAd44)、(SEQ ID NO116，ChAd63)和(SEQ ID NO118，ChAd82)。附圖31A-31J提供了在此公開和要求權利的六鄰體蛋白的胺基酸序列與以下六鄰體蛋白的胺基酸序列的比較C1(SEQ ID NO124)、CV68(SEQ ID NO125)、Pan5(做為選擇稱為CV23)(SEQID NO119)、Pan6(做為選擇稱為CV32)(SEQ ID NO120)和Pan7(做為選擇稱為CV33)(SEQ ID NO121)。六鄰體蛋白的多重序列比對容許技術人員進行與人類腺病毒血清型的建議分類一致的系統發生分析(Rux，J.J.，et al(2003)J.Virol.779553-9566)。
在可選擇的方面，本發明進一步提供了21種其他的黑猩猩腺病毒分離物。包含ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17和ChAd19的樣品根據布達佩斯條約作為原始保藏物於2003年12月12日保藏在歐洲細胞培養物保藏所(ECACC，Porton Down，Salisbury，Wiltshire，SP4 OJG，UnitedKingdom)。指定了保藏物的登記號碼03121201(ChAd4)、03121202(ChAd5)、03121203(ChAd7)、03121204(ChAd9)、03121205(ChAdl0)、03121206(ChAd11)、03121207(ChAd16)、03121208(ChAd17)、03121209(ChAd19)和03121210(ChAd20)。
包含ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的樣品根據布達佩斯條約作為原始保藏物於2005年1月12日保藏在歐洲細胞培養物保藏所(ECACC，Porton Down，Salisbury，Wiltshire，SP4 OJG，United Kingdom)。指定了這些保藏物的登記號碼05011201(ChAd8)、05011202(ChAd22)、05011203(ChAd24)、05011204(ChAd26)、05011205(ChAd30)、05011206(ChAd31)、05011207(ChAd37)、05011208(ChAd38)、05011209(ChAd44)、05011210(ChAd63)和05011211(ChAd82)。
這些保藏物將根據國際承認用於專利程序的微生物保藏布達佩斯條約的條款進行維持。這些保藏僅為了方便本領域技術人員而進行，而不是認可保藏是35 U.S.C.§112所需的。在授予專利之時，除了37 C.F.R.§1.808(b)規定的要求之外，對保藏的材料的公眾可獲得性的所有限制將被不可撤銷地除去。
在其他方面，本發明還提供了複製缺陷性重組腺病毒載體，其能夠感染哺乳動物細胞，優選的人類細胞，並指導編碼的轉基因產物的表達。如在此展示的，所公開的載體(vector)適合用做疫苗載運體(carrier)用於遞送包含免疫原的轉基因，針對所述免疫原的免疫反應是期望的。在特定實施方式中，本發明提供了能夠在人類E1表達(即，包裝)細胞系中高水平複製的重組複製缺陷性黑猩猩腺病毒載體。在一個實施方式中，本發明提供了能夠在PER.C6TM細胞中複製的重組腺病毒。
一般而言，本發明包括的重組載體提供了能避開對腺病毒血清型的先存免疫的疫苗載運體，所述先存免疫是在人類群體中一般遇到的。更具體地說，本發明的重組載體包含載體主幹序列，在此顯示了其缺少與人類腺病毒衍生載體的常見血清型交叉反應的中和B表位。
本發明進一步提供了包括腺病毒部分和質粒部分的類群特異性的穿梭載體，其中所述腺病毒部分一般地包含a)病毒左末端(ITR和包裝信號)、pIX基因的部分和病毒基因組右末端；和b)基因表達盒。採用了在指定為相同血清型亞群(即，A、B、C、D或E亞群)的腺病毒之間觀察到的核苷酸序列同一性設計類群特異性的穿梭載體，並可用於操作在此公開的核苷酸序列，和/或用於克隆屬於相同亞群的其他黑猩猩腺病毒，產生含有刪除了E1區域的黑猩猩腺病毒基因組的腺病毒前質粒(pre-plasmid)。
本發明的其他方面包括包含腺病毒疫苗載體和/或腺病毒前質粒載體的宿主細胞、生產所述載體的方法，包括將所述腺病毒疫苗載體導入表達腺病毒E1蛋白的宿主細胞中，並收穫產生的腺病毒疫苗載體。在特定的實施方式中，本發明提供了生產複製缺陷性黑猩猩腺病毒載體的方法，包括將所公開的腺病毒載體之一導入表達腺病毒E-1的人類細胞，並收穫產生的重組腺病毒。
本發明的另一個方面還提供了包含本發明的腺病毒載體的疫苗組合物。包含重組黑猩猩腺病毒載體的組合物可以單獨施用或與其他基於病毒或非基於病毒的DNA/蛋白疫苗組合施用。它們也可以作為更廣闊的治療方式的部分來施用。這些組合物可以以預防性或治療性的設置施用給哺乳動物宿主，優選人類宿主。如在此所示，單獨地或以組合形式施用所公開的疫苗組合物，例如激發強化方式或不同血清型Ad載體的多次注射，引起哺乳動物中能夠特異性識別由轉基因編碼的免疫原的免疫反應的誘導。
在此公開和要求權利的方法之一，包括向哺乳動物(是幼稚的(naive)或被激發以對目標抗原有免疫活性的)施用足夠量的重組黑猩猩腺病毒載體，所述載體含有它的野生型E1基因的至少一個功能刪除，帶有包含啟動子的序列，所述啟動子能指導編碼至少一個目標抗原的核苷酸序列的表達，其中施用所述重組抗體引發(或激發)抗原特異性免疫反應。
在一個實施方式中，本發明提供了設計以誘導針對傳染原(例如，病毒或細菌性病原體或哺乳動物寄生蟲)的免疫反應(預防性或治療性的)的方法。在第二實施方式中，本發明提供了設計以在哺乳動物中誘導免疫反應的方法，所述免疫反應將破壞對自體抗原，例如TAA的耐受性。本發明的這個方面考慮使用所公開的載體作為疫苗載運體用於製備和施用癌症疫苗。
根據以下對發明的詳細說明，本發明的其他實施方式和益處將顯而易見。
附圖的簡要說明附圖1是概括了用於構建ChAd6穿梭載體(pARS ChAd6-3)的克隆策略的示意圖。
附圖2是說明用於在E.coli菌株BJ5183中通過同源重組克隆ChAd6病毒基因組的克隆策略的示意圖。
附圖3是說明各種ChAd6穿梭質粒的元件的示意圖，包括pARSChAd6-3 GAG；pARS ChAd6-3 SEAP；pARS ChAd6-3 EGFP；和pARS ChAd6-3 NS MUT。
附圖4是說明用於克隆ChAd6ΔE1表達載體的同源重組方案的示意圖。
附圖5A-5K提供了ChAd3的基因組核苷酸序列(SEQ ID NO1)。
附圖6A-6K提供了ChAd6的基因組核苷酸序列(SEQ ID NO2)。
附圖7A-7K提供了CV32的基因組核苷酸序列(SEQ ID NO3)。
附圖8A-8K提供了CV33的基因組核苷酸序列(SEQ ID NO4)。
附圖9A-9J提供了CV23的基因組核苷酸序列(SEQ ID NO5)。
附圖10提供了ChAd20的纖維基因的核苷酸序列(SEQ ID NO6)。
附圖11提供了ChAd4的纖維基因的核苷酸序列(SEQ ID NO7)。
附圖12提供了ChAd5的纖維基因的核苷酸序列(SEQ ID NO8)。
附圖13提供了ChAd7的纖維基因的核苷酸序列(SEQ ID NO9)。
附圖14提供了ChAd9的纖維基因的核苷酸序列(SEQ ID NO10)。
附圖15提供了ChAd10的纖維基因的核苷酸序列(SEQ ID NO11)。
附圖16提供了ChAd11的纖維基因的核苷酸序列(SEQ ID NO12)。
附圖17提供了ChAd16的纖維基因的核苷酸序列(SEQ ID NO13)。
附圖18提供了ChAd17的纖維基因的核苷酸序列(SEQ ID NO14)。
附圖19提供了ChAd19的纖維基因的核苷酸序列(SEQ ID NO15)。
附圖20A-20G提供了以下的纖維蛋白的胺基酸序列ChAd3、ChAd4、ChAd5、ChAd6、ChAd7、ChAd8、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd20、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82，與來自C1(SEQ ID NO85)、CV68(SEQ ID NO86)、PAN5(也稱為CV23)(SEQ ID NO80)、PAN6(也稱為CV32)(SEQ ID NO81)和Pan7(也稱為CV33)(SEQ ID NO82)的參考纖維蛋白序列的比較。
附圖21提供了ChAd20的六鄰體基因的核苷酸序列(SEQ IDNO16)。
附圖22提供了ChAd4的六鄰體基因的核苷酸序列(SEQ ID NO17)。
附圖23提供了ChAd5的六鄰體基因的核苷酸序列(SEQ ID NO18)。
附圖24提供了ChAd7的六鄰體基因的核苷酸序列(SEQ ID NO19)。
附圖25提供了ChAd9的六鄰體基因的核苷酸序列(SEQ ID NO20)。
附圖26提供了ChAd10的六鄰體基因的核苷酸序列(SEQ IDNO21)。
附圖27提供了ChAd11的六鄰體基因的核苷酸序列(SEQ IDNO22)。
附圖28提供了ChAd16的六鄰體基因的核苷酸序列(SEQ IDNO23)。
附圖29提供了ChAd17的六鄰體基因的核苷酸序列(SEQ IDNO24)。
附圖30提供了ChAd19的六鄰體基因的核苷酸序列(SEQ IDNO25)。
附圖31A-31J提供了ChAd3、ChAd4、ChAd5、ChAd6、ChAd7、ChAd8、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd20、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的六鄰體蛋白的胺基酸序列，與來自C1(SEQ ID NO124)、CV68(SEQ ID NO125)、PAN5(也稱為CV23)(SEQ ID NO119)、PAN6(也稱為CV32)(SEQ IDNO120)和Pan7(也稱為CV33)(SEQ ID NO121)的參考纖維蛋白序列的比較。
附圖32提供在此公開的人工序列SEQ ID NO26-40和SEQ IDNO45和46，包括寡聚物和引物的列表。
附圖33是屬於不同血清型亞群(即，C、E和D亞群)的ChAd載體的免疫斷點(break-point)的圖示。通過在用表達gag的ChAd3、ChAd11、ChAd20、CV33、CV68、ChAd6、ChAd9、ChAd10、CV32、ChAd4、ChAd7和ChAd16載體免疫的小鼠中進行滴定實驗，測定引發可測量免疫反應的最低劑量。
附圖34提供了在恆河猴中引發的CEA特異性T細胞反應的圖示，所述恆河猴次序地用人類腺病毒載體(MRKAd5 RhCEA)、12周間隔後用黑猩猩腺病毒載體(CV33 RhCEA)免疫。通過IFN-γELISPOT分析評估免疫反應，數據說明了在不存在(DMSO)和存在恆河猴CEA C和D肽庫的情況下孵化之後每百萬個外周血單核細胞(PBMC)中斑點形成細胞(SFC)的數目。
附圖35提供了用PAUPSEARCH(Wisconsin Package Version10.3，Accelrys Inc.)進行全長六鄰體肽序列的多重序列比對和用TREEVIEW進行可視化和操作得出的人類和黑猩猩腺病毒的系統樹。
附圖36是響應於向預先暴露於hAd5的小鼠施用ChAd3和hAd5gag載體獲得的免疫結果的圖示。免疫後3周通過IFN-γELISPOT使用純化的脾細胞評估細胞介導的免疫。
附圖37是在用ChAd3hCEA和Ad5hCEA免疫的人類CEA轉基因小鼠中引發的抗CEA CMI的動力學的圖示。通過用CEA肽庫刺激的PBMC的ICS評估CMI。結果表示為IFNγ+CD8+/總PBMC的％。
附圖38 A-D是暴露於moi 50、250和1250的不同ChAd載體的不同人類初級細胞的感染效率的圖示，所述ChAd載體表達EGFP並屬於不同的亞群(B、C、D、E)。結果表示為螢光細胞/總細胞的％。
發明的詳細說明如在整個說明書和附隨的權利要求書中使用的，採用以下定義和縮寫術語「盒」是指核酸分子，其包含至少一個要表達的核酸序列以及它的轉錄和翻譯控制序列。改變所述盒，將使摻入了所述盒的載體指導不同序列或序列的組合的表達。在本發明的範圍中，盒中存在的核酸序列通常編碼免疫原。由於工程化的限制性位點存在於5′和3′末端，所述盒可以容易地插入、除去或用另一個盒替換。
術語「順式作用元件」是指調節與它們連接的基因的核苷酸序列。存在於DNA中的順式作用元件調節轉錄，轉錄成mRNA的那些能夠調節RNA加工、轉換(turnover)和蛋白質合成。
術語「載體」是指一些工具，通過它們能將DNA片段導入到宿主有機體或宿主組織中。存在著各種型式的載體，包括質粒、病毒(包括腺病毒)、噬菌體和粘粒。
術語「啟動子」是指在DNA鏈上、RNA聚合酶能與之結合的識別位點。啟動子與RNA聚合酶形成起始複合物來啟動和驅動轉錄活性。通過活化序列例如增強子，或抑制序列例如沉默子，可以修飾所述複合物。
術語「藥學有效量」是指重組腺病毒的數量，在特定施用途徑中有效轉導宿主細胞並提供足夠的轉基因表達水平以引發免疫反應。
術語「有複製能力的」重組腺病毒(AdV)是指具有完整的或功能上必需的早期基因(即，E1A、E1B、E2A、E2B和E4)的腺病毒。野生型腺病毒是有複製能力的。
術語「複製缺陷性」重組AdV是指一種腺病毒，由於已經被工程化以具有病毒複製所必需的基因產物的至少一種功能刪除或完全刪除，而變得不能複製。本發明的重組黑猩猩腺病毒載體是複製缺陷性的。
術語「哺乳動物」是指任何哺乳動物，包括人類。
術語「序列同一性百分比」或「同一性」在核酸序列的上下文中是指當進行最大相關性比對時兩個序列中的相同的殘基。序列同一性比較的長度可以是在基因組的全長上(例如，約36kbp)，基因的開放閱讀框的全長上，蛋白、亞基或酶上[參見，例如，提供腺病毒編碼區域的框]，或至少約500到5000個核苷酸的片段上，是期望的。然而，在例如，至少約九個核苷酸、通常至少約20到24個核苷酸、至少約28到32個核苷酸、至少約36個或更多核苷酸的較小片段之間的同一性也是期望的。類似地，可以對胺基酸序列，在蛋白的全長上或其片段，容易地確定「序列同一性百分比」。適當地，片段長度至少約8個胺基酸，並可以達到約700個胺基酸。在此描述了適合的片段的實例。
在默認設置下使用在此定義的這種算法和電腦程式，容易地確定同一性。優選的，這種同一性是在蛋白、酶、亞基的全長上，或在長度至少約8個胺基酸的片段上進行的。然而，同一性可以基於更短的區域，在所述區域上適合於放入同一的基因產物的用途。
一般地，腺病毒構建體、基因構建體通過參考其中含有的基因來命名。例如，「pChAd3 ΔE1gag」是指包含刪除了E1區域的ChAd3黑猩猩腺病毒基因組的質粒構建體。在這個質粒中，E1區域被免疫原表達盒替代，所述免疫原表達盒包含處在人類CMV啟動子控制下之後是牛生長激素多聚腺苷酸信號的HIV gag基因。類似地，pCV33DE1-E3 NSmut是指在此公開的第二種質粒構建體，其包含刪除了E1和E3區域的CV33黑猩猩腺病毒基因組，所述E1和E3區域被免疫原表達盒替代，所述免疫原表達盒包含處在人類CMV啟動子控制下之後是牛生長激素多聚腺苷酸信號的HCV非結構基因。
縮寫「Ag」是指抗原。
在整個說明書中和在附隨的權利要求中使用的，單數形式「a」、「an」和「the」包括複數的引用，除非上下文中明顯地另外指示了。
腺病毒(Ads)是已經在幾種禽類和哺乳動物宿主中鑑定的無包被的二十面體病毒。人類Ads(hAd)屬於Mastadenovirus屬，包括所有已知的人類和動物(例如，牛、豬、犬、鼠、馬、猿和綿羊)來源的許多Ads。根據許多生物學、化學、免疫學和結構標準，包括大鼠和恆河猴紅血球的血細胞凝集性質、DNA同源性、限制性內切酶裂解模式、G+C含量百分比和致癌性，將人類腺病毒分成六個亞群(A-F)(Straus，1984，In The Adenoviruses，ed.H.Ginsberg，pps.451-498，New YorkPlenus Press，and Horwitz，1990 In Virology，eds.B.N.Fields and D.M.Knipe，pps.1679-1721)。迄今為止，已經鑑定了51種不同的血清型，並根據它們的血細胞凝集性質和生物物理和生物化學標準分類成亞群。
腺病毒顆粒是二十面對稱性的，取決於血清型，直徑為60-90nm。二十面體衣殼由三種主要蛋白，六鄰體(II)、五鄰體基部(III)和隆突纖維(IV)以及許多微小蛋白(即，VI、VIII、IX、IIIa和IVa2)組成(W.C.Russel，J.Gen.Virol.，812573-2604(2000))。在人體中觀察到的先存免疫性的一個方面是體液免疫，其可以引起特異於病毒蛋白的抗體的產生和存留。由腺病毒引發的體液反應主要地針對主要結構蛋白質六鄰體、五鄰體和纖維。
公開的報導已經證實了，包含針對多種血清型的抗體的滴度是常見的(Dambrosio，E.(1982)J.Hyg.(London)89209-219)，先存滴度的重要部分具有中和活性。對腺病毒的中和免疫性是型特異性的(type-specific)，特定血清型的腺病毒的感染僅賦予對該血清型的免疫性。一些報導已經表明，針對六鄰體的抗體是最強烈的和最具中和性的(Toogood，C.I.A.，Crompton，J.and Hay R.T.(1992)J.Gen.Virol.73，1429-1435)。因此，合理的假定是，對型特異性中和作用負責的表位位於七個高變區內，所述高變區是通過對從不同血清型得出的六鄰體序列進行比對來鑑定的。(Crawford-Miksza，L and D.P.Schnurr.(1996)J.Virol.701836-1844)。
已經通過不同的方法，包括免疫血清從處理的動物到幼稚動物的被動轉移，證實了型特異性中和抗體的存在與用基於相同血清型的載體不能引發免疫反應之間的直接相關性。一般而言，對特定病毒血清型的先存體液免疫降低了載體施用的治療效力。此外，施用基於特定病毒血清型的載體引發了針對該載體的、阻止相同血清型的重複施用的免疫反應。
在特定的實施方式中，本發明提供了一種繞過所述不利影響的方法，所述不利影響與對hAd的常見血清型的先存免疫性的後果有關。更具體地，本發明考慮使用以不在人類中傳播的血清型為特徵的黑猩猩腺病毒載體。因此，本發明提供了缺少與常見人類血清型的表位發生交叉反應的中和B細胞表位的腺病毒(Chad)載體作為疫苗載運體。
雖然已經報導了腺病毒特異性細胞介導的免疫性(CMI)可能是交叉反應性的，基於多種血清型的重複注射的疫苗接種研究表現了比基於單個載體的免疫程序更高的效率。這些實驗進一步證明了疫苗目的的載體施用的主要局限是針對該載體的體液性先存免疫性。對使用人類腺病毒作為疫苗載運體有關的難題的可能解決方案包括，施用更高劑量的預測會遭遇先存免疫反應的腺病毒(例如，C亞群血清型)，和使用基於稀有人類血清型的載體。然而，使用更高劑量的疫苗增加了疫苗的成本和不希望的副作用的風險，臨床前測試的結果表明人類的另外的血清型比hAd5和hAd6有更低的免疫原性。
在避免針對載體的腺病毒主幹元件的宿主體液和細胞免疫反應的問題和最小化使用可能被有複製能力的腺病毒(RCA)汙染的人類腺病毒衍生載體成品的風險的嘗試中，已經表徵和開發了幾種非人類腺病毒作為疫苗載運體(Soudois，C.et al(2000)J.Virology，7410639-10649；Farina，S.F.et al(2001)J.Virology，7511603-11613；Cohen，C.J.et al(2002)J.Gen.Virology，83151-155.)。使用非人類腺病毒序列來繞過與先存免疫性有關的難題的前提基於這種觀察結果，即針對常見人類腺病毒血清型的中和抗體不太可能交叉中和非人類病毒。然而，病毒和細胞因素的不相容性給大多數可選擇的載體系統(牛、綿羊、犬)帶來了實際的局限性，其特徵在於必須在非人類細胞系中繁殖的缺點。
Wilson等已經公開了一報告，描述了基於黑猩猩腺病毒68型(CV68)C68的複製缺陷性載體的鑑定，所述腺病毒最初是從黑猩猩的腸繫膜淋巴結分離的(Basnight，M.，et.al.(1971)Am.J.Epidemiol.94166-171.)，CV68被完全測序並發現在整體結構上類似於人類腺病毒(Farina，S.F.et al，J.Virol.75(23)11603-11613(2001))。病毒的基因組長度是36,521鹼基對，已經描述為最類似人類腺病毒的E亞群，與大多數已經測序的人類Ad4開放閱讀框有90％的同一性。CV68 ITRs的長度是130鹼基對，存在所有主要的腺病毒早期和晚期基因。CV68的特徵在於不在人類中傳播(circulate)的血清型，其缺少與常見的人類血清型的表位交叉反應的中和B細胞表位。雖然黑猩猩腺病毒類似於人類腺病毒，但在人類中沒有記錄到針對黑猩猩血清型的交叉反應性中和免疫。(Farina，S.F.et al.J.Virol.(2001)75(23)11603-13)。
來源於CV68的重組載體被描述為足夠類似於人類血清型以支持表達柯薩奇病毒(coxsackievirus)和腺病毒受體的細胞的轉導(Cohen，C.et al.，J.Gen.Virol.83151-155(2002)。重要地，CV68的特徵是與人類腺病毒足夠的相似性水平以支持它在攜帶來自人類腺病毒5型的E1的293細胞中複製(Farina，S.F.et al.，J.Virol.75(23)11603-11613(2001)。此外，根據人類血清型5 E1的側翼序列與CV68衍生載體序列的側翼序列是非同源的這一觀察結果，預計不會發生同源重組。因而，預計CV68衍生的疫苗成品(vaccine stocks)被RCA汙染的可能性很低。
同一組研究者隨後報導了，使用CV68衍生的腺病毒序列作為疫苗載運體用於在小鼠中誘導針對狂犬病病毒糖蛋白的抗體。通過用迷你基因(minigene)盒替換E1A和E1B基因產生了複製缺陷型的CV68。用含有E1刪除、包含編碼狂犬病病毒糖蛋白的轉基因產物的腺病毒重組體(AdC68rab.gp)免疫的小鼠，發展出對狂犬病病毒的保護性免疫，並且對不然就是致死劑量的狂犬病病毒的攻擊保持了抗性(Xiang，Z et al.，J.Virol.76(5)2667-2675(2002)。近來已經報導了表達密碼子優化的、截短形式的HIV-1的gag的第二種CV68構建體在小鼠中誘導強有力的gag特異性CD8+T細胞反應。疫苗誘導反應顯示了能提供對牛痘gag重組病毒攻擊的保護(Fitzgerald，J.C.et al.，J.Immunol.1701416-1422(2003)。對用人類腺病毒血清型5預先免疫的小鼠使用CV68gag或Ad5gag載體進行實驗性疫苗接種展現出，與通過CV68疫苗引發的相比，通過Ad5引發的更顯著的gag特異性T細胞的降低和對病毒攻擊的保護。C68gag疫苗效力的降低是由於Ad5特異性CD8+T細胞的交叉反應性(同上)。
一同考慮這個數據表明，猿衍生的複製缺陷性腺病毒載體與基於常見的人類血清型的載體相比更適合用作人類疫苗載運體。如在此所示，用人類Ad5強烈免疫的小鼠(附圖36)可以用ChAd3-gag腺病毒載體進行免疫的實驗結果表明，先存的抗人類Ad5免疫性不會降低ChAd載體引發的gag特異性CMI反應。這些結果與人類Ad5交叉反應性B和T細胞表位不存在於ChAd3或ChAd6載體中的結論相一致。
一般而言，非常好地表徵了腺病毒基因組，儘管存在幾種不同的血清型，在類似地安置了特定功能的腺病毒基因組的整體結構上存在某些普遍的保守性。在美國專利No.6,083,716(黑猩猩腺病毒載體)和PCT公開的申請WO 03/000851(快速篩選細菌轉化體和新的猿腺病毒蛋白的方法)中提供了Wilson等公開的黑猩猩腺病毒C1和CV68的核苷酸序列，以及每個病毒的E1A、E1B、E2A、E2B、E3、E4、L1、L2、L3、L4和L5基因的位置，通過引用將其中的教導合併在此。
腺病毒基因組的每個末端都包含稱為反向末端重複(ITR)的序列，其是病毒複製必需的。病毒還包含病毒編碼的蛋白酶，其是加工某些結構蛋白所需的，所述結構蛋白是產生傳染性病毒顆粒所需的。根據宿主細胞轉導後病毒基因的表達順序，描述了腺病毒基因組的結構。更具體地，根據轉錄是在DNA複製開始之前還是之後發生，將病毒基因稱為早期(E)或晚期(L)基因。在轉導的早期階段，腺病毒的E1、E2、E3和E4基因被表達以使宿主細胞作好病毒複製的準備。通過刪除病毒基因組的必需的早期區域1(E1)，病毒可以變為複製缺陷性的。Brody et al，1994 Ann N Y Acad Sci.，71690-101。在晚期階段期間，接通了晚期基因L1-L5的表達，它們編碼病毒粒子的結構元件。所有晚期基因都處在單個啟動子的控制之下，編碼的蛋白包括五鄰體(L2)、六鄰體(L3)、100 kDa支架蛋白(L4)和纖維蛋白(L5)，它們形成了新的病毒粒子，腺病毒DNA將被包裹在其中。取決於病毒的血清型，在單個宿主細胞中可以產生10,000-100,000個子代腺病毒粒子。最終，腺病毒複製過程引起細胞的裂解。
通過從公開的黑猩猩核酸序列中刪除特定的核苷酸序列並插入來自其他DNA序列、對轉基因的插入、表達和其他遺傳操作有用的序列，構建了在此公開的複製缺陷性腺病毒載體。因此，在此描述的重組黑猩猩腺病毒可以含有來源於一種或多種黑猩猩腺病毒的腺病毒序列，或來自黑猩猩腺病毒和來自人類腺病毒的序列。可以重組地、合成地產生適合的多核苷酸序列，或可以從天然來源分離。適用於本發明的特定方面的腺病毒序列包括缺少與常見的人類血清型交叉反應的中和B細胞表位的序列。
至少，本發明的重組黑猩猩腺病毒(例如，載體)含有複製和病毒顆粒封裝所需的黑猩猩腺病毒順式作用元件，與至少一個免疫原表達盒組合。一般地，順式作用元件側翼於包含編碼至少一個抗原的轉基因的表達盒。更具體地，本發明的載體含有必需的腺病毒的順式作用5′反向末端重複(ITR)序列(其起到複製起點的作用)、3′ITR序列、包裝/增強子結構域和編碼異源分子的核苷酸序列。無論所述重組載體是僅包含最小的腺病毒序列還是包含僅具有特定基因(例如，E1和/或E3或E4區域)的功能性刪除的完整腺病毒基因組，本發明的載體包含黑猩猩腺病毒衣殼。
一般而言，在此公開的腺病毒載體包含複製缺陷性腺病毒基因組，其中所述腺病毒基因組不具有功能性E1基因，並包含免疫原表達盒，其包含a)編碼至少一個免疫原的核酸，針對該免疫原的免疫反應是期望的；和b)與編碼所述免疫原的核酸序列可操作連接的異源(即，對於所述腺病毒序列而言)啟動子；和轉錄終止子。
更具體地，本發明提供了由重組腺病毒基因組組成的複製缺陷性載體，所述重組腺病毒基因組缺少選自由E1、E2、E3和E4構成的組的至少一個早期基因。在一個實施方式中，通過用免疫原表達盒替換、或破壞在此公開的腺病毒分離物(例如，ChAd3、ChAd6、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAdl9、ChAd20、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63或ChAd82)之一的E1基因來製備複製缺陷性載體。例如，可以通過刪除/破壞ChAd3(SEQ ID NO1)或ChA6(SEQ ID NO2)的E1基因來製備載體。做為選擇，複製缺陷性載體可以從在此公開的其他腺病毒分離物的任何一個來製備，包括ChAd3、ChAd6、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82或ChAd20。在其他實施方式中，本發明的複製缺陷性載體包含來源於已經被任選的工程化而缺少功能性E3基因的、在此公開的ChAds之一的腺病毒基因組。要理解的是，在此公開的黑猩猩腺病毒序列可以通過完全除去早期基因或通過使基因失效或無功能來變成複製缺陷性的。
要理解的是，本發明包括了特徵為具有修飾的載體，所述修飾例如破壞腺病毒表達一種或多種選定基因產物的能力的「功能性刪除」。如在此使用的術語「功能性刪除」寬泛地涵蓋具有使特定基因產物無功能的效果的修飾。一般而言，功能性刪除採取部分或全部刪除腺病毒基因的形式。然而，技術人員將容易認識到，其他操作，包括但不限於進行引入移碼突變的修飾也能實現功能性刪除。例如，本發明的重組黑猩猩腺病毒載體可以通過導入一種修飾來成為複製缺陷性的，所述修飾被設計以幹擾、或功能性刪除所述病毒表達腺病毒E1A和/或E1B的能力。
公知的是，可以通過導入一種修飾來獲得複製缺陷性腺病毒載體，所述修飾被設計以幹擾、或功能性刪除E2基因的組中一個或多個基因的表達。更詳細地，可以通過鈍化聚合酶基因、或前末期蛋白基因或DNA結合蛋白基因來構建複製缺陷性載體。此外，刪除或鈍化E4區域表達的基因是構建複製缺陷性黑猩猩Ad載體的可選擇的策略。可以組合早期基因的刪除或鈍化來產生更為減毒的載體。做為選擇，複製缺陷性ChAd載體也可以包含在其他病毒基因中的另外的修飾，例如晚期基因L1到L5。此外，可以通過組合獲自不同血清型的六鄰體和纖維基因來產生新的腺病毒疫苗載運體。六鄰體和纖維基因混移(shuffling)策略的使用也將容許研究者改變ChAd的生物學性質和促進具有不同的趨性或具有新的血清學特徵的載體的產生。
要理解的是本發明涵蓋重組腺病毒載體，其包含了完整基因或其部分的刪除，所述刪除單獨地或任意組合地有效破壞所修飾的基因的生物學活性。例如，儘管在此所示希望的是與E1基因的功能性刪除相組合向載體中導入異源Ad5 E4序列，還是可以構建重組猿腺病毒，其具有E4區域表達的基因的功能性刪除。做為選擇，可以消除腺病毒延遲早期E3基因的功能；然而由於E3的功能不是重組腺病毒粒子的產生所必需的，不必將該基因產物重新放回以產生能夠包裝在本發明中有用的病毒的重組體。
在本發明的一個實施方式中，使用的複製缺陷性腺病毒載體是含有E1以及任選的E3的刪除的黑猩猩C亞群腺病毒。例如，對於ChAd3，可以將適合的E1刪除/破壞導入從bp 460到bp 3542的區域(參考SEQ ID NO1)。對於ChAd6，可以將適合的E1刪除/破壞導入從bp 457到bp 3425的區域(參考SEQ ID NO2)。對於CV32，E1刪除優選的從bp 456到bp 3416(參考SEQ ID NO3)；對於CV33，E1刪除優選的從bp 456到bp 3425(參考SEQ ID NO4)和對於CV23，E1刪除優選的從bp 456到bp 3415(參考SEQ ID NO5)。對於CV32和CV33，E3刪除優選的分別為從bp 27446到bp 31911(參考SEQ ID NO3)；從bp 27146到bp 31609(參考SEQ ID NO4)。本領域技術人員可以根據序列同源性和多重序列比對容易地確定對於其他黑猩猩分離物的等同序列。
本領域技術人員將容易地認識到，為了構建刪除E1的腺病毒載體，必需考慮載體主幹的結構和包含轉基因的核酸序列的組成來進行許多決定。例如，研究者必需確定E1刪除的大小是否適應轉基因的大小。如果不適應，則必需向載體的主幹中導入另外的刪除。
包含轉基因的核酸序列可以是基因、或基因的功能部分，一般將以表達盒的形式存在。一般地，基因表達盒包括(a)編碼感興趣的蛋白或抗原的核酸；(b)與編碼所述蛋白的核酸可操作連接的異源啟動子；和(c)轉錄終止信號。所述核酸可以是DNA和/或RNA，可以是雙鏈或單鏈的。為了在期望的宿主(例如，哺乳動物宿主)中表達可以對核酸進行密碼子優化。
還必須考慮主幹內要導入轉基因的部位和轉基因的方向來作出決定。更具體地，可以按E1平行(5′到3′轉錄)或反平行(相對於載體主幹在3′到5′方向上轉錄)方向插入轉基因。此外，需要鑑定合適的轉錄調節元件並與所述轉基因可操作地連接，所述轉錄調節元件能夠指導轉基因在哺乳動物宿主細胞中的表達，載體是為所述哺乳動物宿主細胞準備用作疫苗載運體的。「可操作連接的」序列包括與被調節的核酸序列鄰接的表達控制序列，和反式作用的、或在一定距離上來控制所調節的核酸序列的調節序列。
調節序列包括合適的表達控制序列，例如轉錄起始、終止、增強子和啟動子序列；有效的RNA加工信號，例如剪接和多聚腺苷酸信號；增強翻譯效率的序列(例如，Kozak共有序列)；增強蛋白質穩定性的序列和任選的促進蛋白質分泌的序列。這些和其他常見的載體元件的選擇是常規的，許多適合的序列對於本領域技術人員而言是公知的。(參見，例如，Sambrook et al.和其中引用的參考文獻，例如，第3.18-3.26和第16.17-16.27頁，和Ausubel et al.，Current Protocolsin Molecular Biology，John Wiley Sons，New York，1989)。
在特定的實施方式中，所述啟動子是由真核RNA聚合酶識別的異源啟動子(即，對於腺病毒序列而言)。在優選的實施方式中，所述啟動子是「強」或「高效」啟動子。強啟動子的實例是即時早期人類巨細胞病毒啟動子(Chapman et al，1991 Nucl.Acids Res 193979-3986，通過引用將其合併)。可以使用沒有(CMV)或含有內含子A序列(CMV-intA)的人類CMV啟動子，儘管本領域技術人員公認的是可以使用許多其他已知的啟動子，例如強免疫球蛋白或其他真核基因啟動子，包括EF1α啟動子、鼠CMV啟動子、勞氏肉瘤病毒(RSV)啟動子、SV40早期/晚期啟動子和β-肌動蛋白啟動子。
可以用於本發明的啟動子的進一步實例是強免疫球蛋白啟動子、EF1α啟動子、鼠CMV啟動子、勞氏肉瘤病毒啟動子、SV40早期/晚期啟動子和β肌動蛋白啟動子，雖然本領域技術人員可以理解的是根據本發明的方法可以使用能實現預定宿主中的表達的任何啟動子。啟動子可以包含可調節序列，例如Tet操縱子序列。在試圖抑制基因轉錄的情況中，例如提供了調節轉錄和表達的可能性的序列是有用的。
適合的基因表達盒還包含轉錄終止序列。優選的轉錄終止子是牛生長激素終止子。CMVintA-BGH終止子的啟動子/轉錄終止組合是特別優選的，雖然也可以使用其他的啟動子/終止子組合。如在此所示，50個核苷酸長度的牛生長激素終止/多聚腺苷酸信號(bGHpA)或短的合成多聚A信號(SPA)定義如下AATAAAAGATCTTTATTTTCATTAGATCTGTGTGTTGGTTTGTGTG(SEQ ID NO26)。一般而言，例示了適合的終止序列。多聚A信號被插入到包含轉基因的核酸序列之後和3′腺病毒ITR序列之前。
在此描述的重組腺病毒載體可以含有來源於一種或多種腺病毒株的腺病毒序列。適合的序列可以從天然的來源獲得，或重組地、合成地、或通過其他遺傳工程或化學方法產生。在特定的實施方式中，重組黑猩猩腺病毒是包含非黑猩猩腺病毒多核苷酸序列的嵌合重組體。適合的非黑猩猩腺病毒序列可以從人類腺病毒株獲得。例如，可以用hAd5 E4(Ad5 nt 32816到nt 35619)或Ad5E4orf6(Ad5 nt 33193到nt 34077)(Ad5 GenBank登記NoM73260)替換天然的E4區域。
一般而言，由本發明的重組腺病毒載體遞送的免疫原(抗原性分子)包括多肽、蛋白或酶產物，其由與一核苷酸序列組合的轉基因編碼，所述核苷酸序列提供了必需的調節序列來指導所述編碼的產物在宿主細胞中的轉錄和/或翻譯。轉基因的組成取決於載體的預定用途。例如，如果免疫原性組合物是被設計以在哺乳動物宿主中引發特異於傳染原的抗體反應或細胞介導免疫反應，則合適的是使用編碼至少一個免疫原性產物的核酸序列，所述免疫原性產物預計為接受者賦予病原體特異性免疫。做為選擇，如果所述組合物是製備用作癌症疫苗的，適合的轉基因可以包含自體抗原例如TAA的免疫原性部分，其是根據引發足夠效力的保護性免疫反應的目標來選擇的，來破壞對特定TAA的宿主耐受性，和引發足以預防癌症的起始或預防腫瘤發展的、長期的(例如，記憶性)反應。因此，適合的免疫原性基因產物可以從感染哺乳動物宿主的多種病原體(例如，但不限於，病毒、寄生蟲、細菌和真菌)獲得，或從癌症或腫瘤細胞獲得。雖然在此用特定集合的測試免疫原舉例說明了本發明，要理解的是本發明不限於使用在此例示的抗原。更具體地，本發明考慮使用異源的和自體的抗原作為免疫原，包括但不限於TAA。
在一個實施方式中，本發明提供了免疫原性組合物(例如，疫苗)，用於誘導針對由傳染原表達的抗原(即，免疫原)的免疫反應。例如，希望的是引發針對感染人類和/或非人類動物物種的病毒的免疫反應。病毒家族的實例包括小RNA病毒科(Picornaviridae)，其包括六個不同的屬，例如口蹄病毒(Aphtovirus)、心臟病毒(Cardiovirus)、腸道病毒(Enterovirus)、肝病毒(Hepatovirus)、Parechovirus、鼻病毒(Rhinovirus)，針對所述病毒家族的預防性和/或治療性免疫反應是希望的。小RNA病毒的實例是口蹄疫病毒(Foot-and-mouth diseaseviruses)、腦心肌炎病毒(Encephalomyocarditis viruses)、脊髓灰質炎病毒(Polioviruses)、Coxackieviruses、人類肝炎A病毒、人類parechoviruses、鼻病毒，針對所述小RNA病毒的免疫反應是希望的。杯狀病毒科(Caliciviridae)包括與人類中由病毒的Norwalk群引起的流行性胃腸炎和在動物中的其他綜合症有關的不同的屬，所述其他綜合症如在兔中與兔出血病病毒有關的出血性疾病，或在貓中由貓杯狀病毒引起的呼吸道疾病。
另一個病毒家族是星狀病毒科(Astroviridae)，其包含從人類以及許多不同的動物物種分離的病毒，引發針對該病毒家族的免疫反應是希望的。人類星狀病毒與胃腸炎和幼兒的腹瀉有關。做為選擇，給哺乳動物宿主賦予對病毒的披膜病毒科(Togaviridae)的成員的免疫性是希望的，其包括兩個屬甲病毒屬(alphavirus)和rubivirus。甲病毒屬與人類和獸類疾病有關，例如關節炎(即切昆貢亞熱病毒(Chikungunya virus)、辛德畢斯病毒(Sindbis virus))或腦炎(東方馬腦炎病毒(Eastern Equine Encephalitis Virus)、西方馬腦炎病毒(Western Equine EncephalitisVirus))。
風疹病毒提供了可選擇的病毒目標，其是Rubivirus屬的唯一成員，是與發燒和淋巴腺病有關的輕度皮疹疾病暴發的原因。當母親在早期妊娠期間獲得時，風疹病毒感染還與胎兒異常有關。黃病毒科(Flaviviridae)是另一個病毒家族，由三個屬組成黃病毒屬、pestiviruses和肝病毒屬，包括重要的人類以及動物病原體。黃病毒屬成員中的許多是節肢動物傳播的人類病原體，引起各種疾病包括發燒、腦炎和出血熱。登革熱病毒、黃熱病毒、日本腦炎病毒、西尼羅河熱病毒、蜱傳播的腦炎病毒是主要的全球性或地域性(地方性)的病原體。Pestivirus屬包括有主要是經濟上的重要性的動物病原體，例如牛病毒性腹瀉病毒、標準豬瘟病毒(Classical Swine FeverVirus)、邊界疾病病毒(Border Disease Virus)。肝炎C病毒是肝病毒屬的唯一成員，與急性和慢性肝炎有關。重組腺病毒表達的HCV蛋白可以引發保護性的和治療性的免疫反應，限制在世界範圍內影響17000萬人的病毒感染的後果。
做為選擇，來源於冠狀病毒科(Coronaviridae)的成員的抗原可以由重組腺病毒載體表達以獲得對感染的保護。通過用選自包括ChAd3、4、5、6、7、9、10、11、16、17、19、20、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的組的、表達一種或多種SARS-CoV蛋白的一種或多種黑猩猩腺病毒進行免疫，可以獲得對嚴重急性呼吸綜合症冠狀病毒(SARS-Co病毒)的保護，所述SARS-CoV蛋白無限制地包括核殼(N)蛋白、聚合酶(P)蛋白、膜(M)糖蛋白、刺突(S)糖蛋白、小包膜(E)蛋白或由該病毒表達的任何其他的多肽。包括狂犬病病毒的棒狀病毒科(Rhabdoviridae)成員可以是表達病毒蛋白的重組疫苗的目標。
其他可能的目標包括Filoviridae家族，包含Ebola樣病毒和Marburg樣病毒屬，與嚴重的出血熱暴發有關；副粘病毒科(Paramyxoviridae)包含在人類中已知的最流行的某些病毒，如麻疹、呼吸道合胞體病毒、副流感病毒和獸醫感興趣的病毒如新城疫和牛瘟病毒；正粘病毒科(Orthomyxoviridae)包括流感A、B、C病毒；布尼安病毒科(Bunyaviridae)主要由節肢動物傳染到脊椎動物宿主，包含重要的人類病原體，如裡夫特山谷熱(Rift valley fever)、SinNombre、Hantaan、Puumala病毒；沙粒病毒科(Arenaviridae)包含淋巴細胞性脈絡叢腦膜炎、拉沙熱、阿根廷出血熱(ArgentineHemorragic fever)、玻利維亞出血熱(Bolivian Hemorragic fever)病毒；Bornaviridae科包含主要在馬和綿羊中引起中樞神經系統疾病的病毒；呼腸孤病毒科(Reoviridae)包括輪狀病毒，世界範圍內的嬰兒和幼兒中嚴重痢疾性疾病的最重要原因，可以感染人類和其他哺乳動物的環狀病毒(藍舌病、獸疫流行性出血病病毒)；逆轉錄病毒科(Retroviridae)，病毒的一個大組，包含重要的人類病原體如人類免疫缺陷性病毒1和2(HIV-1和HIV-2)和人類T細胞白血病毒1型和2型(HTLV1和2)，以及非人類慢病毒，例如感染綿羊和山羊的Maedi/Visna viruses，感染馬的馬傳染性貧血病毒，感染牛的牛免疫缺陷病毒，感染貓的貓免疫缺陷病毒；多瘤病毒科(Polyomaviridae)包括小的DNA致癌病毒，典型病毒是分別感染小鼠和恆河猴的多形瘤和SV40(從人類患者分離了與SV40近相關的BK和JC病毒)；乳頭狀瘤病毒科(Papillomaviridae)由一組DNA病毒組成，所述病毒感染高等脊椎動物包括人類，產生疣和溼疣。乳頭狀瘤病毒感染與人類和動物中的癌症發展有關。人類乳頭狀瘤病毒與子宮頸癌、陰道癌和皮膚癌有關。皰疹病毒科(herpesviridae)包括一些亞科，在其中分類了許多人類和其他哺乳動物的重要病原體。抗原的適合的來源可以是但不限於單純性皰疹病毒1和2，水痘-帶狀皰疹病毒、Epstein-Barr病毒、細胞巨化病毒、人類皰疹病毒6A、6B和7、卡波西肉瘤相關皰疹病毒。抗原的進一步適合的來源是痘病毒科的成員，如猴痘病毒、Molluscum contagiusum病毒、天花病毒；肝炎B病毒，肝病毒科的典型成員，以及引起急性和/或慢性肝炎的其他病毒如肝炎delta病毒、肝炎E病毒。
本發明的腺病毒載體還適合於製備免疫原性組合物，所述免疫原性組合物被設計以在人類或動物中刺激針對非病毒病原體表達的蛋白的免疫反應，所述病原體包括細菌、真菌、寄生蟲病原體。例如在此公開的載體可以用於製備針對，但不限於Staphylococcus aureus、Streptococcus pyogenes、Streptococcus pneumoniae、霍亂弧菌(Vibriocholerae)、破傷風桿菌(Clostridium tetani)、Neisseria meningitis、Corynebacterium diphteriae、結核分枝桿菌(Mycobacteriatuberculosis)和麻風桿菌(leprae)，Listeria monocytogenes和Legionellapneumofila的疫苗。希望製備預防性或治療性疫苗的真菌和哺乳動物寄生蟲的實例包括白色念珠菌(Candida albicans)、煙曲菌(Aspergillus fumigatus)、Histoplasma capsulatum、Plasmodiummalariae、Leishmania major、Trypanosome cruzi和brucei、Schistosomahaematobium、mansoni和japonicum；Entamoeba histolytica，和已知與人類絲蟲病有關的Filaria的許多種類。
癌症一般涉及編碼多肽的基因的失調，所述多肽有助於維持細胞周期或控制細胞增殖(例如，生長因子、致癌基因、受體和腫瘤抑制物)。涉及癌症的許多基因的產物在各種各樣的腫瘤細胞表面表達。在人類和動物癌症中已經鑑定了可被T和B淋巴細胞識別的多種腫瘤抗原。適用於抗癌疫苗試驗的極大多數腫瘤相關抗原(TAA)被描述為「自體抗原」，因為除了在腫瘤細胞上表達之外，它們還在正常的組織上和/或在胎兒發育期間表達。目標人群對TAA的免疫耐受可以解釋為什麼許多癌症疫苗被證實是無效的。
腫瘤抗原可以通過正常細胞基因的致癌突變體來產生，改變的原癌基因或腫瘤抑制物基因例如，Ras、p53或Bcr-Abl蛋白是可以刺激T/B細胞反應的改變的細胞蛋白的實例。腫瘤抗原可以是在腫瘤細胞中過量表達的正常細胞蛋白(酪氨酸酶、GP100、MART通常在黑素細胞中以低水平表達，在黑素瘤中過量表達)，或在腫瘤細胞中異常表達的正常細胞蛋白(MAGE、BAGE、GAGE在黑素瘤和許多癌中表達，但是在睪丸和胎盤中正常表達)。腫瘤抗原可以是致癌病毒的產物由宮頸癌表達的乳頭狀瘤病毒E6和E7蛋白；由EBV+淋巴瘤和鼻咽癌產生的EBV EBNA-1蛋白；在SV40誘導的實驗腫瘤中的SV40 T抗原。癌胎抗原(oncofetal antigens)在癌細胞和正常發育的(胎兒)組織中高水平表達，但不在成年人組織中表達。癌胚抗原(CEA)和甲胎蛋白(AFP)是良好表徵的癌胎抗原的實例。
新近的證據支持了能引發免疫反應的TAA的存在，因而使這類抗原成為疫苗療法的適合的免疫原。然而，作為一類抗原，TAA是非常不好的免疫原，在T細胞發育期間高度特異於TAA的T細胞不是被刪除了就是被無反應化了。因此，預期的是，攜帶腫瘤的宿主對特定TAA的免疫反應是極其微弱的。由於破壞對目標TAA的宿主耐受性的內在需要，實驗性的臨床疫苗研究特別集中於開發能增強TAA特異性T細胞反應的免疫策略。一般地而言，有效的癌症疫苗必須克服免疫耐受性並且增強宿主的免疫反應到預防性和/或保護性的水平。在許多實驗性疫苗研究中已經將抗腫瘤效果與對TAA的T細胞反應相關聯。
在可選擇的實施方式中，本發明考慮能用於誘導針對腫瘤抗原的免疫反應的免疫原性組合物(例如，癌症疫苗)。適合的組合物將含有包含編碼腫瘤抗原的核酸序列的重組黑猩猩腺病毒，和生理學上可接受的載運體。在特定的實施方式中，盒的編碼序列元件可以編碼單個免疫原，例如，來源於自體抗原的免疫原性肽序列，例如腫瘤相關抗原。在某些實施方式中，編碼免疫原的核酸序列(例如，轉基因)可以是為在特定哺乳動物物種中的表達優化了的密碼子。在其他實施方式中，編碼序列可以編碼超過一個免疫原，例如一種或多種密碼子優化的腫瘤抗原。例如，利用所公開的腺病毒載體的癌症疫苗可以編碼自體抗原的組合，自體抗原例如HER2/neu、CEA、Hepcam、PSA，PSMA、端粒酶、gap100、Melan-A/MART-1、Muc-1、NY-ESO-1、存活蛋白、溶基質蛋白酶3、酪氨酸酶、MAGE3、CML68、CML66、OY-TES-1、SSX-2、SART-1、SART-2、SART-3、NY-CO-58、NY-BR-62、hKLP2、VEGF。
有效的癌症疫苗的開發需要鑑定能在接種的患者中引發抗原特異性免疫的策略和產生在主動免疫結束後能夠留存的免疫反應。策略的成功將取決於針對目標抗原的可測量免疫反應是否與針對癌症的發生或復發的保護作用相關。已經顯示了細胞介導的免疫和體液免疫的效應機制都能殺死腫瘤細胞。然而，來自實驗系統的數據表明，抗原特異性T細胞是消除腫瘤細胞的最強大的免疫機制。效應T細胞對腫瘤特異性抗原(例如，TAAs)的識別預計可容許TAA象腫瘤排斥抗原一樣起作用。公開的研究表明，刺激CD8+和CD4+輔助T細胞反應對於達到最優的腫瘤清除是重要的((Greenberg，P.D.(1991)Adv.Immunol.49281-355；Pardoll，D.M.et al.(1998)Curr.Opin.Immunol.10588-94)。臨床反應(即，效力)已經與分泌幹擾素γ的細胞毒性T細胞的增加相關聯。分析方法的出現，例如在此使用的ELISPOT分析，以展現當前疫苗載運體的效力，容許研究者測量對免疫接種方式的T細胞反應，從而便於癌症疫苗的開發。
癌症疫苗可以是預防性或治療性的。癌症疫苗的預防性用途的一般假定是，在攜帶腫瘤的受試者中TAA是極其弱的免疫原或功能上無免疫原性的。更具體地，在癌症免疫學領域，在患有癌症的患者中疫苗可以用作免疫療法。因此，可以設計癌症疫苗來引發針對TAA的免疫反應，所述TAA由先存的腫瘤或惡性腫瘤表達。因而，在特定的實施方式中，治療性癌症疫苗意圖用於攜帶腫瘤的患者，其發展了對常規治療方式的抗性，或在常規治療後有發展出復發的高可能性。
腺病毒的高免疫原性使得腺病毒載體對用於疫苗載運體的情況是特別好的候選者，所述疫苗載運體被設計以破壞宿主對自體抗原的耐受性。在自體免疫疾病中首先描述的表位或決定簇傳播的現象，已經與MHC I類和MHC II類限制性反應相關聯，並與HER-2/neu蛋白特異性T細胞免疫的發展相關聯。表位傳播代表了對免疫原性蛋白的特定部分的免疫反應的產生，隨後是免疫天然傳播到存在於同一蛋白上的其他抗原決定簇。例如，Disis等在84％的患有過量表達HER-2/neu的惡性腫瘤的患者中觀察到表位傳播，所述患者被施用了疫苗，所述疫苗包含與粒細胞-巨噬細胞集落刺激因子混合的、來源於HER-2蛋白的可能的T輔助表位的肽(J.Clin.Oncol.(2002)20(11)2624-2632)。重要地，表位傳播與HER-2/neu蛋白結構域反應的產生有關，並提示了有效地繞過了免疫耐受性的免疫。
適用於在此公開的腺病毒載體和方法作為癌症疫苗的目標的TAA應當具有許多特徵。例如，目標TAA必須具有有利的表達分布型，意味著與正常組織相比，在腫瘤或惡性組織中它應當優先地表達或過量表達。此外，因為在腫瘤發生中起作用的TAA更有可能在癌症發展的不同階段期間保留，適合的目標TAA還應當在腫瘤發展和轉移的整個階段保持。適合的目標TAA還應當在腫瘤內同質地表達。第三，適合的目標TAA必需不經受絕對的免疫耐受性。更具體地，必須有某些證據，可以識別感興趣的TAA並對其進行應答的T細胞沒有從宿主的T細胞庫中完全地刪除(Berinstein，N.L.，J.Clin.Oncol．29(8)2197(2002)。
癌胚抗原(CEA)具有許多特徵，使它成為用作抗癌疫苗的目標抗原的吸引人的TAA。它是Ig超家族的成員，所述Ig超家族的特點在於有利的表達模式。它在超過50％的所有人類癌症中表達，並與腫瘤發生過程有關，這表明它的表達在整個癌症發展過程中可能是被選擇的和保守的。此外，已經證明對CEA的免疫耐受性不是絕對的。公開的研究確定了，人類T細胞可以識別表達CEA的癌細胞，成為對表達CEA的癌細胞有活性的，並裂解表達CEA的癌細胞(Berinstein，N.L.，J.Clin.Oncol.29(8)2197(2002)。例如，用表達CEA的重組牛痘病毒免疫患者，結合隨後的基於肽的體外刺激，產生了能裂解自體腫瘤的CD8+MHC限制性CTL(Tsang，K.Y.et al.J.Natl.Cancer Inst.，(1995)87982-990)。另外地，報導了手術後用重組CEA免疫結腸直腸癌患者誘導了針對CEA的弱的抗體和細胞反應(Samanci，A.，et al.(1998)Cancer Immunol.Immunother.47131-142.)。進一步的，向診斷患有結腸直腸癌的患者施用抗CEA抗獨特型抗體，產生了抗CEA抗體和獨特型特異性T細胞增殖(Foon，L，A.et al.(1995)J.Clin.Invest.，96334-342)。文獻還表明，可以用幾種不同的疫苗接種方法克服癌症患者中對CEA的耐受性(即，用重組CEA或重組正痘或禽痘-CEA病毒疫苗接種，施用抗獨特型抗體，用CEA激動劑表位脈衝樹突狀細胞)。
CEA是癌胎糖蛋白(oncofetal glycoprotein)，其在正常胎兒結腸中表達，在正常的結腸黏膜中以小得多的程度表達。它還在大多數腺癌，特別是結腸、胰腺、乳房、肺、直腸和胃的腺癌中過量表達。許多結腸直腸癌症和一些癌瘤產生在血清中可測量的高水平的CEA，這使之成為最廣泛使用的惡性腫瘤的血清學標記，特別是在患有結腸直腸癌的患者中。
提供了用於本發明的組合物和方法的適合的免疫原的第二種TAA是HER2/erb-2(也稱為neu)原癌基因的產物。象CEA一樣，HER2/neu具有有利的表達模式，並且不經受絕對耐受性。更具體地，在正常成年人各種組織，包括皮膚和乳房，和胃腸道、生殖道、和泌尿道的組織的上皮細胞中，檢測到低水平的HER2/neu轉錄產物表達和185 kD的多肽產物；在胚胎發育期間在相應的胎兒組織中檢測到更高水平的表達(Press et al.，Oncogene 5953-962(1990)。幾個系列的證據暗示了在人類乳房、肺、前列腺、卵巢、子宮內膜和結腸直腸腫瘤中HER-2的擴增與致瘤性轉化之間的聯繫(Disis and Cheever，Adv.CancerResearch 71343-371(1997)。一般而言，HER2/neu的過量表達與癌症患者的不良預後和較高的復發率有關(Slamon et al.，Science 244707-712(1989)。因而，特異於HER-2/neu蛋白的疫苗在許多不同人類惡性腫瘤的疾病復發預防方面具有廣泛的應用和實用性。
HER2/neu編碼具有內在的酪氨酸激酶活性並顯示了與表皮生長因子(EGF)受體的廣泛同源性的跨膜糖蛋白(Akiyama，T et al.，(1986)Science 2321644-1646)。使用HER2作為癌症免疫療法的靶點的最初的臨床研究之一，採用了HER-2特異性單克隆抗體Herceptin用於乳腺癌的治療(Goldenberg MM(1999)Clin.Ther.21309-318)。這引起了隨後的努力，其集中於使用HER-2作為免疫系統的T細胞支路(arm)的靶點來引發有效的抗瘤反應，包括使用包含HER-2結構域的重組融合蛋白來激活自體抗原遞呈細胞。公開的報導確定了，患有表達neu的乳腺和卵巢癌症的許多癌症患者產生了針對HER2/neu癌基因的蛋白產物的免疫反應(例如，產生抗原特異性抗體和T細胞)。
重組腺病毒序列、轉基因和其他載體元件裝配到各種中間質粒和穿梭載體中，使用所述質粒和載體來產生重組病毒粒子，都可以使用本領域技術人員公知的標準教科書中描述的常規技術來實現(Sambrook et al，Molecular CloningA Laboratory Manual，2ndEd.，Cold Spring Harbor Press，Cold Spring Harbor，NY(1989)。這種技術包括但不限於，常規的cDNA克隆技術、使用來源於腺病毒基因組的重疊寡核苷酸序列、同源重組、聚合酶鏈式反應、標準轉染技術、瓊脂覆層中的病毒斑塊，和其他相關的方法。
為了幫助在原核細胞中製備多核苷酸，常常製備腺病毒載體的質粒型式(腺病毒前質粒)。腺病毒前質粒含有腺病毒部分和質粒部分。腺病毒部分與本發明的腺病毒載體(含有無功能的或刪除的E1和任選的E3區域的腺病毒序列)中包含的腺病毒部分和側翼是方便的限制性位點的免疫原表達盒基本上相同。
腺病毒前質粒的質粒部分常常含有處在原核啟動子的轉錄控制下的抗生素抗性標記，從而抗生素的表達不會在真核細胞中出現。可以使用氨苄青黴素抗性基因、新黴素抗性基因和其他藥學上可接受的抗生素抗性標記。為了有助於在原核生物中通過發酵高水平產生多核苷酸，有益的是腺病毒前質粒含有原核複製起點並且是高拷貝數的。許多商業上可獲得的原核克隆載體提供了這些益處。希望的是除去非必需的DNA序列。同樣希望的是所述載體不能在真核細胞中複製。這將多核苷酸疫苗序列整合到接受者的基因組中的風險最小化。當希望將多核苷酸的表達限制到特定的組織類型時，可以使用組織特異性啟動子或增強子。
可以通過使用腺病毒主幹DNA和合適的穿梭載體(被設計以靶向特定的刪除並將期望的限制性位點摻入產生的質粒中)進行同源重組產生腺病毒前質粒(包含具有期望的刪除和插入的複製缺陷性腺病毒的基因組的質粒)。在這個過程中使用的穿梭載體可以使用本領域廣泛了解和理解的一般方法來產生，例如，考慮期望的刪除來對腺病毒末端進行PCR，將各個片段順序克隆到合適的克隆質粒中。然後可以消化腺病毒前質粒並通過磷酸鈣共同沉澱或其他合適的方法轉染入補足細胞系。然後發生病毒複製和擴增，一種由於顯著的細胞病變效果而變明顯的現象。然後在病毒複製完成之後收穫感染的細胞和培養基(一般地，轉染後7-10天)。
一般而言，在構建和裝配期望的腺病毒前質粒之後，通過轉染表達腺病毒E1的人類細胞系將腺病毒前質粒營救為病毒。在包裝細胞系和載體的病毒基因之間的補充性允許載體中的腺病毒-轉基因序列被複製並包裝到病毒顆粒衣殼中，引起重組腺病毒的生產。可以通過本領域技術人員已知的各種方法的任何一種，來分離和純化產生的病毒，用於本發明的方法。
對本領域技術人員顯而易見的是，當向病毒載體中導入一個或多個選定的黑猩猩腺病毒基因的刪除時，可以在生產過程期間通過在生產細胞系中存在的序列來提供被刪除的基因產物的功能。因而，可以通過永久轉化的細胞系來提供所操作的基因的功能，所述細胞系的特徵是某些或全部腺病毒功能，所述功能是包裝所需的但在載體中是無功能的(例如，E1A、E1B、E2A、E2B、E4的任何一個)。做為選擇，可以用包含必需基因的構建體來感染或短暫地轉染適合的細胞以提供所述功能，來將必需的腺病毒功能提供給適合的包裝細胞系。
因此，本發明還提供了在表達E1的人類細胞系中生產黑猩猩腺病毒載體的方法。更具體地，所公開的載體可以在E1補足細胞系中增殖，包括已知的細胞系293和PER.C6TM。這些細胞系都表達腺病毒E1基因產物。在1997年1月3日公開的WO 97/00326中描述了PER.C6TM，通過引用將其合併在此。它是用E1基因片段轉導的原代人類成視網膜細胞系，所述E1基因片段補足複製缺陷性第一代腺病毒的產生，但被設計以防止通過同源重組產生有複製能力的腺病毒。在Graham et al(1977)J.Gen.Virol 3659-72中描述了293細胞，也通過引用將其合併在此。本領域技術人員將認識到術語「第一代腺病毒」是指複製缺陷性腺病毒，其是E1區域無功能的或刪除了E1區域的，並任選的是E3區域無功能的或刪除了E3區域。
意圖用作臨床試驗中的疫苗組合物的複製缺陷性腺病毒載體的批次應當經證明是無RCA的(Fallaux，F.J.et al(1998)Human GeneTherapy，91909-1917)。實際上，這是勞動密集的過程，需要建立和使用昂貴的篩選程序。本領域技術人員將認識到，高頻率的RCA產生不僅引起生產的批次的高失敗率，還嚴重地限制了規模擴大的努力。消除載體的核苷酸序列和存在於輔助生產/包裝細胞系的基因組中的腺病毒序列之間的同源性，將消除生產的載體批次被同源重組產生的RCA汙染的可能性。
一般地，重組複製缺陷性腺病毒載體在提供E1基因產物in trans的細胞系中增殖。當載體來自相同的或非常相似的血清型時，提供必需的E1基因產物in trans是非常有效的。例如，公知的是刪除了E1(即，ΔE1)的C群血清型(Ad2和Ad5)載體，可以在含有並表達Ad5 E1區域的293或PER.C6細胞中增殖。然而，已經觀察到，存在於293和PER.C6生產細胞中的Ad5 E1序列可能不總是完全地補足非C群血清型的複製。因此，C亞群以外的刪除E1的血清型，例如，來自A、B、D、E和F亞群的那些，在293或PER.C6細胞中可能以比相應wt病毒更低的效率複製，或可能根本不複製。這可能是由於Ad5(C亞群)E1 B 55K基因產物不能夠建立與非C群血清型的E4 orf6基因產物的功能性相互作用。
在表達Ad5 E1的細胞中複製效率的降低根據不同亞群的載體而變化。雖然來自D和E亞群腺病毒的ΔE1載體可以以可變的效率在293和Per.C6TM細胞中被營救(rescue)和增殖，B亞群ΔE1載體的增殖被完全地削弱了(Vogels R，et al.(2003)Aug.Replication-deficienthuman adenovirus type 35 vectors for gene transfer and vaccinationefficient human cell infection and bypass of preexisting adenovirusimmunity.J Virol.77(15)8263-71).
儘管Ad5 E1b 55k和載體表達的E4 orf6蛋白之間的相互作用在相同亞群的成員內是保守的，當表達非C血清型的E4 orr6蛋白時它可能不是足夠穩定的。E1B-55K/E4-orf6複合物的這種低效或不穩定形成引起了ΔE1載體的降低的增殖的缺乏。因此，已經經驗性確定的是，為了成功地和有效地營救B群血清型的重組腺病毒，需要產生表達感興趣血清型的E1區域的細胞系。在表達Ad5E1的細胞如293或Per.C6TM中，表達可以限於E1b 55K蛋白。做為選擇，可以修飾適合的Ad5E1表達細胞系以便除了Ad5E1之外還表達完整的Ad5 E4區域(或僅E4 orf6)。表達Ad5 E1和orf6的細胞系的產生，在補足可選擇的腺病毒血清型方面是有用的；參見，例如，Abrahamsen et al.，1997 J.Virol.8946-8951。E4(orf6)摻入到Ad5補足細胞系是已知的，產生in trans提供血清型特異性E1基因產物的血清型特異性細胞系也是已知的。做為選擇，非C群載體增殖的效率可以通過用Ad5 orf6取代天然的E4區域修飾病毒主幹來改善。用來自Ad5或其他C亞群病毒(Ad1、Ad2、Ad6)的orf6僅替換天然的orf6也可以得到類似的結果。美國專利No.5,849,561公開了在還表達Ad5-E4基因的部分的Ad5-E1補足細胞系中補足刪除E1的非C群腺病毒載體。
授權給Vigne等的美國專利No.6,127,175公開了穩定轉染的哺乳動物細胞系，其表達腺病毒的E4區域的一部分，優選的是orf6/orf6/7。這種細胞系對於補足E4區域中的重組Ad基因組缺陷是有用的。
包含所公開的腺病毒載體的組合物，包括疫苗組合物，是本發明的重要的方面。這些組合物可以以預防性或治療性的設置施用給哺乳動物宿主，優選的人類宿主。可能的宿主/接種者包括但不限於靈長類和特別是人類和非人靈長類，並包括有商業或馴養的獸醫學重要性的任何非人哺乳動物。包含重組黑猩猩腺病毒載體的組合物可以單獨施用或與其他基於病毒或非基於病毒的DNA/蛋白疫苗組合施用。它們也可以作為更廣闊的治療方式的部分來施用。
在本發明的特定實施方式中，所公開的載體可以用於被設計以破壞宿主對自體抗原或腫瘤相關抗原的耐受性的免疫方案。許多TAA的鑑定已經允許了開發用於癌症治療的主動疫苗接種方法。被加工和呈遞的細胞表面抗原和細胞內抗原都提供了有用的靶點。一般而言，所公開的破壞宿主對自體抗原的耐受性的方法包括(a)通過施用包含第一ChAd載體或質粒載體的第一疫苗組合物來刺激對自體抗原的抗原特異性反應，所述第一ChAd載體或質粒載體攜帶編碼自體抗原的核苷酸序列，針對所述自體抗原的抗原特異性免疫反應是期望的，和(b)通過施用包含不同的血清型的重組ChAd載體的第二疫苗組合物來維持和擴展(a)的免疫反應，所述重組ChAd載體含有其基因組E1基因的至少一個功能性刪除，並且在E1基因的位置上含有包含啟動子的序列，所述啟動子能指導編碼在激發步驟中釋放的相同自體抗原的DNA的表達，從而宿主產生具有破壞對自體抗原的耐受性的效果的免疫反應。
因此，技術人員可以使用這種公開內容來設計可能適用於破壞宿主耐受性的幾種不同的免疫方案。例如，可能的是使用一種方案，其中第一或激發免疫包含質粒DNA，所述質粒DNA編碼特定的自體抗原，例如TAA，任何隨後的免疫包含ChAd載體。包含編碼自體抗原的核苷酸序列的質粒DNA序列可以在一次或多次注射中，有或者沒有電刺激地、肌肉內地遞送。例如，基於通過電穿孔多次(例如，3或4或5次)肌肉注射編碼TAA的質粒DNA，隨後一次或多次肌肉注射包含編碼相同TAA的轉基因的ChAd載體的免疫方案，被在此公開和要求權利的一般方法包括。
做為選擇，破壞耐受性的適合的方案可以包括用包含編碼自體抗原的轉基因的ChAd或hAd載體進行一次或多次激發免疫，隨後用相同的ChAd載體或已知與用於激發免疫的載體不是交叉反應性的、不同的ChAd載體進行一次或多次強化免疫。例如，使用ChAd3激發和用ChAd6進行強化，或用ChAd3激發隨後用ChAd6和ChAd9進行強化的免疫方案可以用於破壞宿主耐受性。在特定的實施方式中，本發明考慮使用包含選自以下構成的組的至少一個腫瘤相關抗原的自體抗原HER2/neu、CEA、EpCAM、PSA、PSMA、端粒酶、gap100、Melan-A/MART-l、Muc-1、NY-ESO-1、存活蛋白、溶基質蛋白酶3、酪氨酸酶、MAGE3、CML68、CML66、OY-TES-1、SSX-2、SART-1、SART-2、SART-3、NY-CO-58、NY-BR-62、hKLP2、VEGF。在特定的實施方式中，本發明提供了通過向患有癌症的哺乳動物遞送編碼TAA的重組黑猩猩腺病毒、誘導針對特異於選定惡性腫瘤的腫瘤相關抗原的免疫反應(例如，體液或細胞介導的)的方法。在本發明的這個方面的優選實施方式中，引發的免疫反應構成了以抗原特異性CD4+和CD8+T細胞的產生為特徵的免疫反應。
本發明的免疫原性組合物可以以預防性或治療性的設置(setting)施用給哺乳動物宿主，優選的人類宿主。可能的宿主/接種者包括但不限於靈長類和特別是人類和非人靈長類，並包括有商業或馴養的獸醫學重要性的任何非人哺乳動物。包含重組黑猩猩腺病毒載體的組合物可以單獨施用或與其他基於病毒或非基於病毒的DNA/蛋白疫苗組合施用。它們也可以作為更廣闊的治療方式的部分來施用。用於本發明的方法的適合的組合物可以包含本發明的重組病毒載體，結合生理學上可接受的成分，例如緩衝液、生理鹽水或磷酸鹽緩衝鹽水、蔗糖、其他鹽和聚山梨酸酯。在肌肉注射時它不引起組織刺激。優選的是冷凍待用的。任選的，本發明的疫苗組合物可以配製為含有其他成分，例如但不限於，佐劑、穩定劑、pH值調節試劑，或防腐劑。這些成分是本領域技術人員公知的。
預想的是，本發明的重組黑猩猩腺病毒以「有效量」施用給人類或獸醫學上的宿主，所述「有效量」是重組病毒的數量，其是有效的以在選定的施用途徑下轉導宿主細胞並提供轉基因的足夠表達水平來引發給接受者/疫苗接種者(vaccine)賦予治療效益或保護性免疫的免疫反應。
導入疫苗接受者的疫苗組合物中病毒粒子的數量取決於使用的轉錄和翻譯啟動子的強度和表達的基因產物的免疫原性。一般地，免疫或預防有效劑量的1×107到1×1012個粒子(即，1×107、2×107、3×107、5×107、1×108、2×108、3×108、5×108或1×109、2×109、3×109、5×109)，和優選的約1×1010到1×1011個粒子直接施用到肌肉組織中。皮下注射、皮內導入、壓過皮膚，和其他施用模式，例如腹膜內的、靜脈內的或吸入遞送也是考慮的。
本發明的重組黑猩猩腺病毒載體可以單獨地、作為混合形式的激發/強化疫苗接種方式的部分、或在基於不同載體血清型的多次注射的組合的接種方式中來施用。一般地，將包含至少一個免疫原的激發劑量施用給哺乳動物宿主，所述哺乳動物宿主需要針對特定病原體或自體抗原的有效免疫反應。這種劑量有效地激發免疫反應，從而在隨後的抗原鑑定中，宿主能夠立即產生針對該免疫原的增強的或強化的免疫反應。利用用於激發和強化的可選擇製劑的混合形式疫苗接種方案可以引起增強的免疫反應。激發-強化施用一般包括激發(通過病毒載體、質粒、蛋白，等)受試者至少一次，容許經過預定長度的時間，然後強化(通過病毒載體、質粒、蛋白，等)。通常採用多次免疫，一般1-4次，儘管可以使用更多次數。激發和強化之間的時長一般可從約四個月到一年，雖然本領域技術人員理解的是可以使用其他的時間範圍。在中和免疫性變得明顯之前，每種載體的多次注射可以在約2周的時間範圍(time frame)內施用。
在本發明的某些實施方式中，給予疫苗超過一次的腺病毒疫苗載體施用，可以以伴有質粒疫苗的施用的方式來給予。與在此公開的載體組合使用的適合的質粒疫苗包括編碼至少一個免疫原的質粒，針對所述免疫原的激發的或強化的免疫反應是期望的，和異源啟動子，其能夠指導編碼免疫原的核酸序列的表達，可操作地與免疫原編碼序列連接，和轉錄終止序列。
例如，可以使用一種劑量給藥方式，其利用不同血清型的重組複製缺陷性黑猩猩腺病毒載體的多次注射。做為選擇，可以給予個體第一劑量(即，激發劑量)的質粒疫苗，和第二劑量(即，強化劑量)，其包含複製缺陷性重組黑猩猩腺病毒載體，所述載體包含在質粒疫苗中遞送的相同免疫原的編碼序列。做為選擇，可以給予個體第一劑量編碼至少一個免疫原的人類腺病毒疫苗載體，隨後是第二劑量，其包含在此公開的複製缺陷性重組黑猩猩腺病毒載體，所述載體包含與在激發劑量中遞送的相同的免疫原的編碼序列。在第二個可選擇的實施方式中，可以首先施用包含本發明的載體的疫苗組合物，隨後施用質粒疫苗。在這些實施方式的任何一個中，可以以病毒載體或質粒形式給予個體多劑量的相同免疫原。可以有預定的最小時間量，來分隔施用。
除了通過本發明的重組複製缺陷性黑猩猩腺病毒載體遞送感興趣的單個蛋白或抗原之外，可以通過獨立的運載體(vehicle)或通過相同的運載體來遞送兩種或多種蛋白或抗原。可以將多個基因/功能等同物連接到適當的穿梭質粒，來產生包含多個開放閱讀框的腺病毒前質粒。多個基因/功能等同物的開放閱讀框可以可操作地連接到不相同的啟動子和轉錄終止序列。
如在此所示，適合的免疫方式可以採用不同的腺病毒血清型。這種方案的一個實例是包含第一血清型，例如ChAd3或ChAd6的重組腺病毒載體的激發劑量，隨後是包含第二血清型的重組黑猩猩腺病毒載體的強化劑量。在可選擇的實施方式中，激發劑量可以包含獨立的腺病毒運載體的混合物，每種腺病毒運載體包含編碼不同蛋白/抗原的基因。在這種情況下，強化劑量也可以包含載體的混合物，每種載體包含編碼獨立的蛋白/抗原的基因，條件是強化劑量施用重組病毒載體，所述重組病毒載體包含編碼與激發劑量中所遞送的相同或相似組的抗原的遺傳物質。可以進一步組合這些多基因/載體的施用形式。進一步處在本發明的範圍內的在於，組合的用藥方式，其包括來自特定抗原的多個但各不相同的成分。
使用不被針對人類載體的病毒元件的先存免疫性中和的、來源於黑猩猩腺病毒的重組載體，提供了對於使用人類Ad載體作為疫苗載運體的替代性選擇。由於腺病毒是高度免疫原性的，腺病毒載體對用於疫苗載運體的情況是特別好的候選者，所述疫苗載運體被設計以破壞宿主對自體抗原的耐受性。此外，以能夠與人類病毒相比較的效率、在人類細胞中，特別是在Per.C6TM細胞系中增殖黑猩猩病毒的能力，從調節的角度和從治療劑或疫苗的大規模產生的角度都提供了相當大的益處。因此，本發明提供了一組黑猩猩腺病毒序列、載體和質粒，容許製備重組病毒，所述重組病毒可單獨地或組合地用作遺傳疫苗接種的疫苗載運體。
為了描述和公開可能與本發明相聯繫使用的方法和材料，在此提及的所有出版物通過引用合併。在此的任何內容都不能解釋為承認本發明沒有資格根據在先的發明在日期上早於這種公開。
參考附圖描述了本發明的優選的實施方式，要理解的是本發明不限於這些明確的實施方式，由本領域的技術人員可以實行各種改變和修改而不背離如附隨的權利要求中所定義的本發明的範圍和精神。
以下實施例說明、但不限制本發明。
實施例1ChAds黑猩猩腺病毒分離物的分離、克隆、測序和表徵在NIRC(New Iberia Research Center 4401 W.Admiral DoyleDrive New Iberia，LA′70560)，在病毒轉運培養基(VTM；MicrotestM4-R Multi Microbe Transport Medium，Remel Inc.)中收集大便樣本，然後冷凍，或直接在-70℃冷凍。樣本保持冷凍在＜-70℃，直到對它們進行處理用於接種到細胞培養物中。在那時，將樣本解凍，然後在過量的冷卻的病毒轉運培養基中渦旋。在樣本分離成懸浮液之後，在1500-1800rpm將它們離心10分鐘。將上清液連續過濾通過0.8和0.2μm針筒過濾器，然後將過濾了的材料接種到細胞培養物中(200-250μL進入殼瓶(shell vial)，200-300μL進入試管培養物)。將每種處理過的樣本接種到播種了293細胞或A549細胞的試管培養物和殼瓶培養物中。
每次接種一組樣品時製備對照(陽性和陰性)培養物。一旦已經接種了set-up中的所有殼瓶，將它們在室溫下以2000rpm(900×g)離心60±10分鐘。在轉子停止旋轉後立即從離心機取下小瓶以防止培養物中的熱破壞。離心之後，從殼瓶中吸出接種物，在每個小瓶中使用新鮮的無菌Pasteur吸管以防止交叉汙染。每次用1.0mL新鮮培養基洗滌培養物三次。洗滌三次之後將新鮮培養基(1.0mL)移液到每個小瓶中，將殼瓶置於孵化器中35-37℃三到四天(約96hr)。
在培養期結束時，從培養物吸出上清液，用免疫螢光分析(IFA)緩衝液每次使用約1.0mL緩衝液洗滌每個小瓶中的細胞層兩次。通過向每個小瓶添加1.0mL冷卻的丙酮(2-8℃ 10分鐘)來固定細胞。用與殼瓶蓋片相關的樣本標識數字標記清除了丙酮的載玻片。使用初級小鼠抗腺病毒抗體[MAB8052，Chemicon]處理殼瓶蓋片進行腺病毒感染的細胞的螢光標記。藉助於螢光顯微鏡評估載玻片。使用10×物鏡掃描每個製備物，記錄免疫螢光覆蓋加樣孔的程度(1+到4+)。使用40×物鏡證實特異性免疫螢光的存在或不存在。如對殼瓶所描述的按相同的順序對試管培養物進行接種(例如，首先是陰性對照、隨後是臨床樣本和陽性對照)。容許接種物在36-38℃吸附60-120分鐘。在吸附期之後，從試管中吸出樣本/對照，用新鮮培養基替代。
接種後三到四天，和此後的一周一次，從培養試管中吸出培養基，用1.5mL新鮮培養基替換。接種後的至少21天內至少每隔一天視覺上監視培養試管的CPE。用黑猩猩樣本接種的培養物與對照進行比較，並通過觀察CPE程度評級。14天後沒有顯示CPE的培養物轉移到新鮮的試管培養物；21天後CPE陰性的培養試管考慮為陰性的。具有3-4+CPE的培養試管進行渦旋10秒。使用無菌的1.0mL血清學吸管從試管的壁上刮下細胞，懸浮在培養物上清液中。之後用樣本標識數字和日期標記5mL扣帽試管(snap cap tube)，保存在-70℃。將500μL細胞懸液從培養試管轉移到扣帽試管中，在2-8℃保存至多一天，直到使用間接免疫螢光抗體技術進行處理來檢測腺病毒(相當於染色殼瓶的步驟)。
黑猩猩腺病毒擴增野生型黑猩猩腺病毒CV32、CV33、CV23和CV68購自ATCC(ATCC登記號CV32，VR-592；CV-33，VR-593；)，或購自EsoterixInc.Austin，Texas，原始分離物如下通過使用表達E1的人類細胞系PER.C6TM或293來增殖。簡要地，將細胞培養在Dulbecco′s ModifiedEagles培養基(DMEM；GibcoBRL，Life Technologies)中，其補充有10％胎牛血清(FBS GibcoBRL，life Technologies)、1％青黴素-鏈黴素、2mM穀氨醯胺和10mM MgCl2(Per.C6TM)。在補充有5％馬血清(GibcoBRL，Life Technologies)的DMEM中進行腺病毒感染。當100％的細胞展現出病毒誘導的細胞病變效應(CPE)時，收集感染的細胞和培養基，通過三個循環的冷凍和解凍來裂解。
在擴增的第一次傳代之後，通過感染播種在96孔平板中的293細胞來克隆所有野生型黑猩猩腺病毒(CV)成品(stocks)。通過對在病毒擴增的第一次傳代獲得的細胞溶胞產物進行限制稀釋，來進行病毒克隆。挑取五個分離的克隆並順序地增殖。在擴增的3-4次連續傳代之後，在種植在5個雙層細胞工廠(NUNC)(200百萬細胞/細胞工廠)的細胞上進行大規模的腺病毒製備。通過在氯化銫密度梯度上的兩個超離心步驟從細胞溶胞產物獲得純化的病毒粒子。
病毒基因組DNA的測序通過在1％SDS-TEN中用蛋白酶K(0.5mg/ml)消化(55℃ 2小時)，從3×1012pp的純化的病毒製品分離基因組DNA。在苯酚-氯仿萃取和乙醇沉澱之後，將基因組DNA重懸浮在水中，提供用於基因組測序。
為了全長Ad基因組測序，將純化的病毒DNA霧化以產生隨機剪切的片段。用E.coli DNA聚合酶和多核苷酸激酶的克列諾片段(klenow fragment)將DNA片段平端化。平端片段在低熔點瓊脂糖凝膠上跑動以純化大小範圍在1-3kb的片段，並克隆到pUCl9載體的SmaI位點以產生獵槍文庫(shotgun library)。連接物用於轉化感受態XL1-Blue MRF。通過在含X-gal和IPTG的LB瓊脂上的白色/藍色篩選鑑定陽性菌落。從文庫中分離出質粒DNA的三到四個96孔板(block)，用pUC正向和反向引物測序。使用Phred-Phrap軟體包篩選所有測序讀數的質量和載體序列。將通過了篩選的讀數裝配成鄰接物(contigs)。設計引物來直接測序腺病毒DNA用於封閉缺口，並確定兩個末端的DNA序列。
對選定的病毒獲得了完整的病毒基因組序列，包括ChAd3(SEQID NO1)、ChAd6(SEQ ID NO2)、CV32(SEQ ID NO3)、CV33(SEQ ID NO4)和CV23(SEQ ID NO5)。表1提供了數據，總結了ChAd3、ChAd6、Pan5(CV23)、Pan6(CV32)、Pan7(CV33)、C1和C68腺病毒基因組的核苷酸序列之間的同一性百分比。使用作為FASTA程序包版本2的部分的ALIGN程序計算比對(William R.Penson，University of Virginia；Myers Miller，CABIOS 1989，411-17)。
表1.黑猩猩腺病毒基因組之間的核苷酸序列同一性百分比ChAd3ChAd6Pan5Pan6Pan7C1 C68ChAd3100 68.1 68.568.268.364.2 68.0ChAd6 100 95.594.595.573.6 91.4Pan5 100 94.996.773.9 92.7Pan6 100 95.173.6 91.3Pan7 100 73.8 93.0C1 100 74.3C68 100為了表徵新的腺病毒分離物(例如，ChAd20、ChAd4、ChAd5、ChAd7、ChAd8、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82)，也通過引物步進(primerwalking)確定了六鄰體和纖維基因的核苷酸序列。纖維基因SEQ IDNO6-15(SEQ ID NO6，ChAd20)；(SEQ ID NO7，ChAd4)；SEQ ID NO8，ChAd5)；SEQ ID NO9，ChAd7)；SEQ ID NO10，ChAd9)；SEQ ID NO11，ChAd10)；SEQ ID NO12，ChAd11)；SEQ ID NO13，ChAd16)SEQ ID NO14，ChAd17)，SEQ ID NO15，ChAd19)和(SEQ ID NO58，ChAd8)，(SEQ ID NO60，ChAd22)，(SEQ ID NO62，ChAd24)，(SEQ ID NO64，ChAd26)，(SEQ ID NO66，ChAd30)，(SEQ IDNO68，ChAd31)，(SEQ IDNO70，ChAd37)，(SEQ ID NO72，ChAd38)，(SEQ ID NO74，ChAd44)，(SEQ ID NO76，ChAd63)和(SEQ ID NO78，ChAd82)。
附圖20A-20G提供了在此公開和要求權利的ChAd分離物的纖維蛋白的胺基酸序列的比較。
在以下列出了六鄰體基因序列SEQ ID NOS16-25(SEQ IDNO16，ChAd20)；SEQ ID NO17，ChAd4)；SEQ ID NO18，ChAd5)；SEQ ID NO19，ChAd7)；SEQ ID NO20，ChAd9)；SEQID NO21，ChAd10)；SEQ ID NO22，ChAd11)；SEQ ID NO23，ChAd16)；SEQ ID NO24，ChAd17)SEQ ID NO25，ChAd19)，(SEQ ID NO97，ChAd8)，(SEQ ID NO99，ChAd22)，(SEQ IDNO101，ChAd24)，(SEQ ID NO103，ChAd26)，(SEQ ID NO105，ChAd30)，(SEQ ID NO107，ChAd31)，(SEQ ID NO109，ChAd37)，(SEQ ID NO111，ChAd38)，(SEQ ID NO113，ChAd44)，(SEQ ID NO115，ChAd63)和(SEQ ID NO117，ChAd82)。附圖31A-31J提供了在此公開和要求權利的ChAd分離物的六鄰體蛋白的胺基酸序列的比較。
黑猩猩腺病毒分類根據已經建議的人類腺病毒血清型(分為六個亞群)的分類(Horowitz，MS(1990)Adenoviridae and their replication.In VirologyB.N.Fields and D.M.Knipe，eds(Raven Press，New York)pp.1679-1740)將不同的黑猩猩腺病毒株分類，通過使用Align X程序(Informax，Inc)進行胺基酸和核苷酸序列比對來得出。
通過查看不同限制性內切酶的病毒基因組限制性圖譜和通過分析六鄰體基因的高變區7(HVR7)的序列，得到新的分離物的初步分類。為此，對側翼於HVR7的高度保守區域設計兩個引物，TGTCCTACCAR CTCTTGCTTGA (SEQ ID NO.45)和GTGGAARGGCACGTAGCG(SEQ ID NO.46)。使用純化的病毒DNA或粗的293溶胞產物作為模板通過PCR擴增HVR7，然後測序。根據HVR7序列分析，我們將新分離的病毒分類入對人類腺病毒所提出的亞群(A-F)(Horowitz，MS(1990)Adenoviridae and theirreplication.In Virology B.N.Fields and D.M.Knipe，eds(ravenPress，New York)pp.1679-1740)。
通過比對人類和黑猩猩腺病毒六鄰體胺基酸序列獲得附圖35中呈現的系統樹。該結果與根據使用Align X程序(Informax，Inc)限於六鄰體HVR7的核苷酸序列比對的初步分類相一致。由採用PAUPSEARCH(Wisconsin Package Version 10.3，Accelrys Inc.)進行的全長六鄰體肽序列的多重序列比對得出該樹，並用TREEVIEW進行可視化和操作。使用Wisconsin程序包中安裝的PAUPSEARCH程序進行Bootstrap置信度分析。對於每個比對，使用「HeuristicSearch」作為檢索條件和Maximum Parsimony作為最優條件將程序運行1000次重複，報告的置信度值取自50％majority-rule consensus。
實施例2ChAd穿梭載體和表達載體的構建以及營救載體的構建和營救使用適合的穿梭載體通過同源重組將基因組病毒DNA克隆到標準質粒載體中，所述穿梭載體含有來源於病毒基因組的左末端和右末端的病毒DNA序列(附圖2)。如以下更完整地描述的，採用在分類為相同血清型亞群的病毒之間觀察到的序列同源性來開發類群特異性穿梭載體。分類為D和E亞群的黑猩猩腺病毒的基因組病毒DNA結果是足夠同源的，容許構建通用穿梭載體來克隆屬於這兩個亞群的病毒。
D/E亞群穿梭載體的構建完全地測序了ChAd6病毒基因組(SEQ ID NO2)，獲得的信息用於構建穿梭載體以便於通過D和E亞群黑猩猩腺病毒的同源重組來進行克隆。
在附圖1中描述了構建ChAd6穿梭載體，在此稱為pARSChAd6-3。附圖32提供了用於在此描述的克隆實驗的寡核苷酸序列的列表(SEQ ID NO26-40和SEQ ID NO45-46)。簡要地，通過用寡核苷酸5′-ATGGAATTCGTTTAAACCATCATCAATAATATACCTC-3(SEQ ID NO27) 和5′-CGCTGGCACTCAAGAGTGGCCTC-3』(SEQ ID NO28)通過PCR擴增來自ChAd6 DNA的左末端的457 bp，用EcoRI和SnaBI消化並克隆入EcoRI-SnaBI酶切的pNEBAd35-2，產生pNEBChAd6-LI。通過使用寡核苷酸5』-ATGAAGCTTGTTTAAACCCATCATCAATAATATACCT-3』(SEQ ID NO29)和5』-ATCTAGACAGCGTCCATAGCTTACCG-3』(SEQ ID NO30)通過PCR擴增右側ChAd6 ITR(bp 36222到bp36648)，用限制性內切酶HindIII和XbaI消化並克隆入HindIII-XbaI消化的pNEBChAd6-LI，產生pNEBChAd6-RLI。最後，與ChAd6基因組DNA序列的核苷酸3426-3813相應的DNA片段用寡核苷酸5′-ATGCTACGTAGCGATCGCGTGAGTAGTGTTTGGGGGTGGGTGGG-3』(SEQ ID NO31)和5′-TAGGCGCGCCGCTTCTCCTCGTTCAGGCTGGCG-3』(SEQ ID NO32)擴增，用SnaBI和AscI消化，然後與SnaBI-AscI消化的pNEBChAd6-RLI連接，從而產生pNEBChAd6-RLIdE1。
為了改善在DH5αE.coli菌株中的重組和質粒增殖的效率，通過PmeI消化從pNEBChAd6-RLIdEl切下含有ChAd6的左側和右側ITR以及pIX基因片段的1306 bp片段，並轉移到不同的質粒載體，所述質粒載體通過用寡核苷酸5′-GATCTAGTTAGTTTAAACGAATTCGGATCTGCGACGCG-3』(SEQ ID NO33)和5′TTCGATCATGTTTAAACGAAATTAAGAATTCGGATCC-3』(SEQ ID NO34)通過PCR擴增從pMRKAd5SEAP獲得。這個最終的連接步驟產生ChAd6穿梭載體pARSChAd6-3。
C亞群穿梭載體的構建完全地測序了ChAd3病毒基因組(SEQ ID NO1)，獲得的信息用於構建穿梭載體以便於通過C亞群黑猩猩腺病毒的同源重組來進行克隆。
簡要地，用於克隆C亞群黑猩猩腺病毒的穿梭載體，在此稱為pChAd3EGFP，如下構建用寡核苷酸5′-TATTCTGCGATCGCTGAGGTGGGTGAGTGGGCG-3』(SEQ ID NO35)和5′TAGGCGCGCCCTTAAACGGCATTTGTGGGAG-3』(SEQ ID NO36)通過PCR擴增含有pIX編碼區的ChAd3 DNA片段(nt 3542-4105)，用SgfI-AscI消化，然後克隆到用SgfI-AscI消化的pARSCV32-3中，產生pARS-ChAd3D。用寡核苷酸5′CGTCTAGAAGACCCGAGTCTTACCAGT-3』(SEQ ID NO37)和5′-CGGGATCCGTTTAAACCATCATCAATAATATACCTTATT-3』(SEQ ID NO38)通過PCR擴增ChAd3右末端(nt 37320-37441)，用XbaI和BamHI消化，然後連接到用XbaI和BamHI限制的pARS-ChAd3D，產生pARS-ChAd3RD。用寡核苷酸5′-ATGGAATTCGTTTAAACCATCATCAATAATATACCTT-3』(SEQ ID NO39)和5′-ATGACGCGATCGCTGATATCCTATAATAATAAAACGCAGACTTTG-3』，(SEQ ID NO40)通過PCR擴增ChAd3病毒DNA左末端(nt 1-460)，用EcoRI和SgfI消化，然後克隆到用EcoRI和SgfI消化的pARS-ChAd3RD，從而產生pARS-ChAd3RLD。還設計病毒DNA盒以含有位於兩個ITR的末端的限制性內切酶位點(Pmel)，從而消化將從質粒DNA釋放病毒DNA。
B亞群穿梭載體的構建根據已經描述的C和D/E亞群穿梭體構建的策略，構建B亞群穿梭體。簡言之，通過用ChAd30的相應片段取代左側末端、pIX區域、右側末端來修飾pARS-ChAd3RLD。此外，用克隆在ChAd30 E4啟動子的控制下的Ad5 E4orf6替代ChAd30的E4區域。該穿梭質粒命名為pChAd30 EGFP穿梭載體。
ΔE1黑猩猩腺病毒載體的構建B亞群通過在E.coli菌株BJ5183中進行同源重組來構建B亞群黑猩猩腺病毒載體。用BstEII和Bstl107I消化的pChAd30EGFP穿梭載體與ChAd8和ChAd30，純化的病毒DNA，共轉化BJ5183細胞。在pIX基因、存在於線性化pChAd30EGFP穿梭體和病毒基因組DNA末端的右側ITR DNA序列之間的同源重組，容許它插入到質粒載體中，同時刪除被EGFP表達盒替換的E1區域。構建根據人類細胞巨化病毒(HCMV)啟動子和牛生長激素多聚腺苷酸信號(BghpolyA)的表達盒，來表達分泌的鹼性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS區域(如附圖3中對ChAd6穿梭載體所描述的)以及腫瘤相關抗原如來自人類和恆河猴來源的CEA和HER2/neu。所有表達盒都通過同源重組插入到ChAd30載體中。
C亞群通過在E.coli菌株BJ5183中進行同源重組來構建C亞群黑猩猩腺病毒載體。用BstEII和Bstl107I消化的pChAd3EGFP穿梭載體與ChAd3、ChAd11、ChAd19和ChAd20純化的病毒DNA共轉化BJ5183細胞。在pIX基因、存在於線性化pChAd3EGFP和病毒基因組DNA末端的右側ITR DNA序列之間的同源重組，容許它插入到質粒載體中，同時刪除被EGFP表達盒替換的E1區域。構建根據人類細胞巨化病毒(HCMV)啟動子和牛生長激素多聚腺苷酸信號(Bgh polyA)的表達盒，來表達分泌的鹼性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS區域(如附圖3中對ChAd6穿梭載體所描述的)以及腫瘤相關抗原如來自人類和恆河猴來源的CEA和HER2/neu。
D和E亞群為了根據D和E亞群黑猩猩腺病毒構建ΔE1載體，用AscI消化穿梭載體pARS ChAd6-3，與CV32、CV33、CV68、ChAd4、ChAd5、ChAd6、ChAd7、ChAd9、ChAd10、和ChAd16純化的病毒DNA共轉染入E.coli菌株BJ5183。在來自pIX基因的DNA序列和存在於線性化pARS ChAd6-3和病毒基因組DNA末端的右側ITR DNA序列之間的同源重組，容許它插入到質粒載體中，同時刪除E1區域(附圖2和4)。
構建根據人類細胞巨化病毒(HCMV)啟動子和牛生長激素多聚腺苷酸信號(Bgh polyA)的表達盒，來表達分泌的鹼性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS基因(附圖3)以及腫瘤相關抗原如人類和恆河猴來源的CEA和HER2/neu。所有的表達盒都插入到pARS ChAd6-3載體的單個SnaBI位點，以通過同源重組轉移到如附圖4描述的ΔE1腺病毒前質粒中。
ΔE1載體的營救和擴增種植在6cm細胞培養平皿上的5×106個PER.C6TM細胞用通過核酸內切酶消化從質粒序列釋放的10微克克隆病毒載體轉染。使用Lipofectamine(Invitrogen)進行DNA轉染。轉染後5-10天收集轉染的細胞和培養基，通過冷凍和解凍裂解。然後通過在293或PER.C6TM細胞上連續傳代來擴增營救的載體。通過感染種植在5-10個細胞工廠(NUNC，Inc.)上總共1-2×109個細胞來進行大規模的擴增。通過兩次運行超速離心機，在氯化銫梯度上獲得純化的載體製品，相對含10％甘油的PBS進行透析，以等分量保存在-70℃。
實施例3中和研究為了評估針對在此公開的黑猩猩腺病毒的中和抗體在人類血清中的流行度，進行中和分析。該分析評估了血清預孵化對攜帶分泌鹼性磷酸酶(SEAP)基因的黑猩猩腺病毒轉導人類293細胞的能力的影響。中和滴度被定義為給出在有單獨的病毒的陽性對照中觀察到的SEAP活性的50％降低的血清稀釋度。
將CV33-SEAP、CV32-SEAP和ChAd3-SEAP載體的2×106到1.5×107個物理粒子稀釋在100μl完全培養基中，添加到稀釋於完全培養基中的等體積的人類或黑猩猩血清中。在各種稀釋度測試每種血清樣品(從1/18稀釋度開始的五個4倍的增加，到1∶4608)。將樣品在37℃預孵化一小時，然後添加到播種於96孔平板(3×104細胞/孔)中的293細胞。孵化一小時後除去接種物，用新鮮培養基重新餵養細胞，24小時後，移出50μl的培養基，通過化學發光分析測量SEAP活性。中和滴度被定義為給出在有單獨的病毒的陽性對照中觀察到的SEAP活性的50％降低的血清稀釋度。測試一組100個人類血清的ChAd中和活性。並行的用Ad5 SEAP載體測試相同的組。
表2.針對黑猩猩腺病毒的中和抗體的流行度
表2中提供的結果表明了針對來源於黑猩猩腺病毒的載體的中和抗體在人類血清中的極低的流行度。僅四份血清顯示了對於CV32載體的超過閾值200的滴度，而8份顯示了對於ChAd3 SEAP載體的超過200的滴度。相反地，檢查的黑猩猩血清的組顯示了抗黑猩猩Ad免疫性的非常高的流行度。這些發現證實了如所預期的，基於黑猩猩Ad的載體具有非常小的機會在人類中被中和。因此它們是對先存的抗人類Ad免疫性難題的理想解決方案，所述免疫性限制了基於常見人類Ad血清型例如Ad5的病毒載體的施用。
實施例4ChAd載體向性(tropism)通過在不同組織來源的人類初級細胞的組上的EGFP表達，來評定Ad5和ChAd載體介導的基因轉移效力。根據廠家的指示培養人類軟骨細胞、成骨細胞、角質形成細胞、黑素細胞、骨骼肌細胞和黑素細胞。如所描述的獲得人類單核細胞、不成熟的和成熟的樹突狀細胞(DC)(Romani，N.et al.1996，J.Immunol.Methods，196，137.)。通過FACS分析檢測轉導的螢光細胞。測試的人類初級細胞的組(panel)包括在心血管疾病、類風溼性關節炎、組織工程(骨骼、皮膚和軟骨)和疫苗接種領域對基於體內以及體外基因轉移的不同治療策略很重要的靶細胞。附圖38A-D中呈現的結果表明，如不同細胞類型感染的不同效率所展現的，不同的黑猩猩腺病毒可以識別除CAR以外的受體。
鼠免疫研究方法和材料免疫方案和脾細胞/PBMC製備免疫用在0.1ml緩衝液中稀釋的選定腺病毒免疫小鼠。每個載體劑量分成兩個50μl的等分量，注射到小鼠的兩個四頭肌中。
脾細胞製備注射後3周處死小鼠，切除它們的脾臟，轉移到10mlR10中(10％FCS、55mM 2-巰基乙醇、1M HEPES緩衝液、2mM L-穀氨醯胺、RPMI培養基1640中的1X青黴素-鏈黴素溶液)。通過鋼篩切碎脾臟，用2ml R10洗滌篩子之後，將脾細胞轉移到50ml Falcon試管中，在室溫(rt)以1200rpm離心10分鐘。除去上清液，添加3mlACK裂解緩衝液(Gibco BRL Formulation#79-0422DG)。室溫下孵化細胞5分鐘。添加45ml 1X PBS，如上述對試管進行離心。用30ml R10洗滌之後，將細胞重懸浮在5ml R10中，通過70m尼龍細胞過濾器(Falcon 2350)過濾。用990μl Turk′s溶液(Merck 040417345)稀釋10μl的細胞，進行計數。最後將細胞稀釋到R10中的107細胞/ml。
外周血單核細胞(PBMC)製備將小鼠血液樣品(150μl)轉移到含50μl PBS/2％EDTA的2ml eppendorf試管。向每個試管添加1mlACK緩衝液。輕輕地混合併在RT孵化5分鐘。樣品在微離心機中以1500rpm離心5分鐘。棄去上清液，組合來自相同的免疫群(immunizedcohorts)的白血球沉澱。重複ACK緩衝液孵化，然後將PBMC的沉澱重懸浮在1ml R10培養基中。
IFN-γELISPOT分析用以2.5μg/ml的濃度在PBS中稀釋的純化的大鼠抗小鼠IFN-γ單克隆抗體(Pharmingen，cat.551216)以100μl/孔包被Millipore MAIP45平板，在4℃孵化過夜(o/n)。用無菌的PBS洗滌平板兩次，通過在CO2孵化器中與200μl/孔的R10孵化2小時來封閉非特異性結合位點。在表達HIV gag的Ad載體的免疫實驗中，將9-mer的肽(AMQMLKETI，Balb/C小鼠中定位的CD8 HIV gag表位)(SEQ IDNO47)在R10中稀釋到2μg/ml，以50μl/孔的數量添加到孔中。在用HCV-NS表達載體進行的免疫實驗中，使用了一肽庫，其覆蓋了NS3解旋酶結構域和代表解旋酶結構域中包含的定位的CD8表位的9-mer肽。通過覆蓋完整胺基酸序列的重疊的15-mer肽的庫，來評估表達人類CEA抗原的ChAds的免疫試驗。作為對照使用DMSO和伴刀豆球蛋白A。以5×105和2.5×105的數量向每個孔中添加細胞。在CO2孵化器中o/n孵化之後，用0.05％Tween 20/PBS洗滌平板，添加在分析緩衝液(5％FBS、0.005％Tween20、PBS)中稀釋1/250的50μl/孔的生物素化大鼠抗小鼠IFN-γ單克隆抗體(PharMingen cat.554410)。在4℃孵化平板o/n，如上進行洗滌。在分析緩衝液中將鏈黴抗生物素蛋白-鹼性磷酸酶結合物(BD554065)稀釋1/2500，以50μl/孔的數量添加，室溫2小時。洗滌之後，向平板添加50μl/孔的BCIP/NBT1-step溶液(Pierce 34042)進行顯影。通過用去離子水洗滌孔停止反應。通過ELISPOT讀數器自動地對斑點計數。
鼠IFN-γ細胞內染色(ICS)將脾細胞稀釋為2×106細胞每1ml R10，用如上所述相同的抗原以2μg/ml的濃度刺激。作為對照，使用DMSO和葡萄球菌腸毒素B(SEB)。在CO2孵化器中過夜孵化之後，用FACS緩衝液(1％FCS、0.01％NaN3、PBS)洗滌細胞，將純化的抗小鼠CD16/CD32 Fc片段(克隆2.4G2，Pharmingen cat.553142)稀釋1/25，以100μl/樣品的數量添加，在4℃孵化15分鐘。在FACS緩衝液中洗滌細胞，以100μl/樣品的數量添加在FACS緩衝液中1∶50稀釋的結合APC的抗小鼠CD3e(克隆145-2C11，Pharmingen#553066)、結合PE的抗小鼠CD4(克隆L3T4，BD Pharmingen cat.553142)和結合PerCP的抗小鼠CD8a(克隆53-6.7，Pharmingen cat.553036)。將細胞室溫孵化30分鐘，洗滌，固定並滲透化(permeabilized)(Becton Dickinson，FACSPerm 2)，與在PermWash(100μl/樣品)中1∶50稀釋的結合FITC的抗小鼠IFN-γ(Pharmingen cat.554411)在室溫孵化30分鐘。洗滌後的細胞重懸浮在500μl 1％甲醛/PBS中，使用CellQuest軟體(BectonDickinson)在FACS-Calibur流動細胞計數器上，進行細胞內細胞因子染色(ICS)分析。
實施例5ChAd載體在小鼠中引發強烈的CMI反應使用表達HIV gag轉基因的載體在小鼠中評估在此公開的ChAd載體引發細胞介導的免疫反應(CMI)的能力。簡要地，用從105直到1010vp/小鼠的成十倍增加劑量的不同載體注射5隻Balb/C小鼠的各組。
注射後三周通過對脾細胞中gag特異性CD8+T細胞進行定量來確定免疫反應的強度。在體外用產生Balb/C小鼠中定位的gag CD8+T細胞表位的肽進行刺激之後，通過ELISPOT分析或通過IFN-γ細胞內染色和FACS分析來測定分泌INF-γ的CD8+T細胞的數量。
從5個免疫的動物獲得結果，在表3中報告，表示為每106個脾細胞中的斑點形成細胞。顯示的是，在與9-mer CD8+gag表位或與gag肽庫孵化之後每百萬個脾細胞的斑點形成細胞的數量。gag肽庫由重疊10aa、涵蓋完整的gag序列的20aa的肽組成。陽性值以粗體報告。
表3中提供的數據表明，施用在此公開和要求權利的ChAd載體引發了強烈的細胞介導的免疫反應，其是能夠與hAd5引發的反應相比較的。通過察看引起陽性免疫結果的最低載體劑量(免疫斷點)，我們對不同載體的效力進行了評分，C亞群ChAd3gag是最有效的，斷點在106pp載體劑量。免疫斷點的評分在附圖33中示出。
表3.用黑猩猩Ad載體免疫的Balbc小鼠中的gag特異性T細胞反應
實施例6ChAd3和CV33 GAG載體引發以GAG特異性CD8+T細胞為特徵的CMI反應為了表徵響應於包含HIV gag轉基因的ChAd載體而引發的CMI反應，來自用不同劑量的載體免疫的五隻小鼠的群組(cohorts)的脾細胞庫通過細胞內IFN-γ染色進行分析。表3和表4中顯示的數據是在獨立的實驗中採集的。
將脾細胞稀釋為2×106細胞每1ml R10，用如上所述相同的抗原以2μg/ml的濃度刺激。作為對照，使用DMSO和SEB(葡萄球菌腸毒素B)。在CO2孵化器中o/n孵化之後，用FACS緩衝液(1％FCS、0.01％NaN3、PBS)洗滌細胞，將純化的抗小鼠CD16/CD32 Fc片段(克隆2.4G2，Pharmingen cat.553142)稀釋1/25，以100μl/樣品的數量添加，在4℃孵化15分鐘。在FACS緩衝液中洗滌細胞，以100μl/樣品的數量添加在FACS緩衝液中1∶50稀釋的結合APC的抗小鼠CD3e(克隆145-2C11，Pharmingen#553066)、結合PE的抗小鼠CD4(克隆L3T4，BD Pharmingen cat.553142)和結合PerCP的抗小鼠CD8a(克隆53-6.7，Pharmingen cat.553036)。將細胞室溫孵化30分鐘，洗滌，固定並滲透化(permeabilized)(Becton Dickinson，FACSPerm 2)，與在PermWash(100μl/樣品)中1∶50稀釋的結合FITC的抗小鼠IFN-γ(Pharmingen cat.554411)在室溫孵化30分鐘。洗滌後的細胞重懸浮在500μl 1％甲醛/PBS中，使用CellQuest軟體(BectonDickinson)在FACS-Calibur流動細胞計數器上進行分析。
表4提供了數據，總結了作為gag特異性CD8+或CD4+T細胞的gag特異性CD3+T細胞的百分比。陽性結果以粗體報告。在此提供的數據表明，由來源於分類為不同血清型亞群(即，C、D和E亞群)的病毒的ChAd載體引發的免疫反應的細胞分布型是類似的，所有gag特異性反應都主要以CD8+T細胞為特徵。此外，注意到，在高的載體劑量下，在所有免疫實驗中gag特異性CD4+反應都變得明顯。ICS分析證實了ChAd3載體可以以106載體劑量刺激抗gag CD8+反應。
表4.用不同亞群的黑猩猩腺病毒載體免疫的小鼠中gag特異性T細胞的表徵
實施例7ChAd載體引發HCV NS特異性T細胞反應相對於MRKAd6NSmut的效力，在C57/Black6小鼠中評估了CV32-NSmut和CV33-NSmut載體的效力。動物注射了從107開始直到109vp/小鼠的成10倍增加的載體劑量。單次注射後3周，通過用再生NS3蛋白的解旋酶結構域中定位的CD8+T細胞表位的9-mer肽刺激T細胞，通過IFN-γELISPOT和IFN-γ細胞內染色來分析CMI。表5中提供的數據總結了不存在(模擬的(mock))或存在NS3 9-mer肽的孵化之後每百萬個脾細胞的斑點形成細胞的數目。
數據表明，表達HCV-NS的CV32和CV33載體都刺激強烈的T細胞反應。根據通過注射109vp/劑量獲得的對CV32載體的第一個陽性結果的觀察，CV32DE1E3 NSmut載體的免疫效力好像比人類C亞群Ad6DE1E3 NSmut載體低大約100倍。用MRKAd6NSmut的平行試驗表明，107vp/動物的劑量足夠刺激細胞介導的免疫。因此，這些結果證實了，在用表達gag的載體的實驗中也觀察到的(參見表3)、相對於人類C亞群載體(例如hAd5和hAd6)，CV32衍生的載體的更低的免疫效力。
表5.在用Mrkad6 Nsmut、CV32NSmut或CV33NSmut免疫的小鼠中的HCV NS特異性T細胞反應
實施例8抗Ad5的先存免疫性不取消ChAd3gag引發的抗gagCMI為了評估針對高血清型流行度的Ad5的先存免疫性對ChAd3免疫的影響，在0和2周在四頭肌中兩次注射1010vp的Ad5wt來預先免疫各5隻BalbC小鼠的4個群組。作為對照，各5隻小鼠的兩個群組在相同的時間點僅用緩衝液注射。然後用106和107vp/小鼠的Ad5gag或ChAd3gag載體免疫Ad5預免疫的小鼠的群組。用106和107vp/小鼠的Ad5gag或ChAd3gag載體免疫對照(幼稚)小鼠的群組。
在第4周通過如上所述的中和分析使用Ad5和ChAd3 SEAP載體評估抗Ad5和ChAd3中和免疫性。對用含有在BalbC小鼠中定位的gag表位的gag 9-mer肽刺激的純化脾細胞進行ELISPOT分析來評估抗gag免疫性。在附圖36中報告的結果證明，抗Ad5免疫性不取消ChAd3gag引發的抗gag CMI，而如所預料的，抗Ad5免疫性完全地阻斷了Ad5gag免疫。
實施例9ChAd3hCEA免疫在表達人類CEA的轉基因小鼠中引發強烈的CEA特異性免疫反應還在表達人類CEA的轉基因小鼠(Clarke，P et al.Cancer Res.(1998)58(7)1469-77.)中評估了在此公開和要求權利的ChAd載體引發針對自體抗原的免疫反應從而破壞耐受性的能力。
用已經描述的1010vp ChAd3hCEA或Ad5hCEA在四頭肌中注射各8隻小鼠的群組。在用包含從aa 497到末端(aa 703)的人類CEA胺基酸序列的15-mer肽的庫刺激的PBMC上，每周監視針對CEA的免疫反應，直到第75天。通過ICS確定響應於CEA肽庫孵化的分泌幹擾素-γ的CD4-CD8+T細胞，來評估抗CEA免疫性。
在附圖37中報告的結果表明，與表達相同轉基因的Ad5相比，ChAd3hCEA載體免疫刺激了針對人類CEA的更加持久的CD8+T細胞反應。
靈長類免疫研究方法和材料免疫方案還評估了在此公開和要求權利的ChAd載體在恆河猴(在此稱為猴)中引發CMI的能力。麻痺恆河猴(開他敏/甲苯噻嗪)，使用結核菌素注射器(Becton-Dickinson)以0.5mL等分量向兩個三角肌中肌肉內遞送疫苗。在所有情況中，恆河猴體重在3-10公斤之間，在1mL緩衝液中施用每個疫苗的總劑量。
從在免疫期間的幾個時間點收集的血液樣品製備血清和外周血單核細胞(PBMC)。所有動物照料和處理都根據動物照料和使用委員會機構(Institutional Animal Care and Use Committee)提供的標準，根據Guide for Care and Use of Laboratory Animals，Institute ofLaboratory Animal Resources，National Research Council中闡述的原則進行。
ELISPOT分析根據早先描述的方案(Allen et al.，2001 J.Virol.75(2)738-749)進行對恆河猴的IFN-γ ELISPOT分析，有某些修改。對於gag特異性刺激，從涵蓋完整HIV-1 gag序列具有10-aa重疊的20-aa的肽製備肽庫(Synpep Corp.，Dublin，CA)。對於HCV NS特異性刺激，從涵蓋NS3到NS5b的完整HCV-NS序列的具有10-aa重疊的15-aa肽製備6個肽庫。
用涵蓋完整蛋白序列的具有10-aa重疊的15-aa肽進行HER2/neu和CEA特異性刺激。
向每個加樣孔添加50μL 2-4×105個外周血單核細胞(PBMC)；使用Beckman Coulter Z2粒子分析儀以設置在80fL的較低的尺寸截止(cut-off)對細胞進行計數。將50μL培養基或每種肽的濃度為8μg/mL的gag肽庫添加到PBMC。樣品在37℃，5％CO2孵化20-24小時。相應地發展出斑點，用根據ImagePro平臺(Silver Spring，MD)定製的成像儀和自動計數子程序處理平板；將計數值標準化為106個細胞輸入。
細胞內細胞因子染色(ICS)向1ml的2×106pBMC/mL完全RPMI培養基(17×100mm圓底聚丙烯試管(Sarstedt，Newton，NC))中，添加抗hCD28(克隆L293，Becton-Dickinson)和抗hCD49d(克隆L25，Becton-Dickinson)單克隆抗體到1μg/mL的終濃度。對於gag特異性刺激，添加10μL的肽庫(每種肽0.4mg/mL)。對HCV NS特異性刺激使用類似的條件。在37℃孵化試管1小時，之後添加20μL的5mg/mL布雷菲德菌素A(brefeldin A)(Sigma)。在37℃、5％CO2、90％溼度孵化細胞16小時。向每個試管添加4mL PBS/2％FBS，在1200rmp 10分鐘將細胞團粒化。將細胞重懸浮在PBS/2％FBS中，使用幾種螢光標記的mAbs對表面標記進行染色(30分鐘，4℃)每試管20μL抗hCD3-APC，克隆FN-18(Biosource)；20μL抗hCD8-PerCP，克隆SKI(BectonDickinson，Franklin Lakes，NJ)；和20μL抗hCD4-PE，克隆SK3(Becton Dickinson)。這個階段的樣品處理在黑暗中進行。洗滌細胞，在750μL 1×FACS Perm緩衝液(Becton Dickinson)中在室溫下孵化10分鐘。將細胞團粒化，重懸浮在PBS/2％FBS中，添加0.1μgFITC-抗hIFN-γ，克隆MD-1(Biosource)。孵化30分鐘後，洗滌細胞並重懸浮在PBS中。使用Becton Dickinson FACSCalibur儀器的所有四個彩色通道對樣品進行分析。為了分析數據，首先除去(gated)低的側向和前向分散的淋巴細胞群體；將用於細胞因子陽性事件的常用的螢光截止用於CD4+和CD8+群體，並用於樣品的模擬和gag肽反應試管。
實施例10在猴中使用ChAdΔE1-gag載體的同源激發-強化方式引發Gag特異性T細胞在第0周和第4周給予各3隻動物的群組肌肉注射任何一種以下構建體1010vp的CV-32ΔE1-gag；或1010vp CV33ΔE1-gag；或1010vp和108vp的MRKAd5ΔE1gag。以規律的4周間隔收集的PBMC在ELISPOT分析中進行分析。結果在表6中提供，其表明不存在(模擬)或存在Gag肽庫的情況下孵化之後每百萬個PBMC中斑點形成細胞的數目，確定了CV32ΔE1gag和CV33ΔE1gag能夠在非人靈長類中誘導顯著水平的gag特異性T細胞。有趣的是注意到，在單次劑量之後(第4周)，CV32ΔE1-gag反應與MRKAd5ΔE1-gag 108vp劑量相當，比MRKAd5-gag 1010vp/劑的更低。CV33ΔE1-gag 1010vp/劑誘導了與MRKAd5-gag 1010vp/劑的反應相當的反應。在第8周第二劑之後證實了這個結果。
表6.用Mrkad5ΔE1-Gag、CV32ΔE1-Gag、CV33ΔE1-Gag免疫的猴中的Gag特異性T細胞反應
實施例11在異源的激發-強化方案中ChAd載體引發HCV NS特異性T細胞反應在獨立的實驗中，在第0、4周以108或1010vp每隻動物向兩隻和三隻猴的組給予MRK Ad6NSoptmut載體的免疫接種。在第24周以相同的劑量用相同的病毒對動物進行強化，在第104周以1010vp每隻動物用CV33-NSmut再次強化。結果在表7和8中呈現，其總結了不存在(模擬的)或存在HCV NS肽庫的孵化之後每百萬個PBMC的斑點形成細胞的數目。
在第一劑之後第4周在注射了1010vp的動物中(表8)，和在第8周(第2劑以後)在注射了108的動物中(表7)，通過IFN-γELISPOT評定的T細胞免疫性顯示了峰值反應。第24周的注射沒有使反應強化(「同源強化」)而在注射CV33-NSmut之後觀察到強烈的強化效果(「異源強化」)。
表7.用108vp/動物的MRK Ad6NSoptmut免疫和用CV33-Nsmut強化的猴中的HCV NS特異性T細胞反應
表8.用1010vp/動物的MRK Ad6NSoptmut免疫和用CV33-Nsmut強化的猴中的HCV NS特異性T細胞反應
在第二實驗中評估用黑猩猩Ad載體異源強化的效率。在第0周和第4周用MRKAd5gag(1010vp/動物)、MRKAd6NSmut(1010vp/動物)或用兩種載體的組合(每個載體1010vp/動物)免疫各三隻猴的群組，然後在第24周用相同的免疫原強化(同源強化)。用相同的免疫原進行同源強化；用CV33gag、CV32 NSmut或用組合的這兩種載體進行異源強化。表9中提供的結果總結了不存在(模擬的)或存在HCV NS肽庫的孵化之後每百萬個PBMC的斑點形成細胞的數目。
在第51周用CV33gag(1010vp/動物)、CV32NSmut(1010vp/動物)和用兩種載體的組合(每種載體1010vp/動物)再次強化相同的群組。在表9中提供的結果進一步表明，由於反應低於注射第一劑疫苗後第4周觀察到的峰值，同源強化不是很有效。在用異源黑猩猩載體免疫接種後在第54周通過IFN-γELISPOT測量到強烈的強化效果。
表9.在用MRK Ad5gag或MRK Ad6NSoptmut以1010vp/動物免疫的猴中，黑猩猩Ad載體的免疫接種有效地強化Gag和HCV NS特異性T細胞反應
實施例12用包含TAA的ChAd載體進行疫苗接種在猴中破壞耐受性並引發TAA特異性T細胞反應在各四隻猴的群組中進行實驗，所述實驗被設計來確定黑猩猩腺病毒載體是否有足夠的免疫原性來破壞對自體抗原的耐受性，並記錄黑猩猩載體用於強化人類腺病毒載體激發的免疫反應的實用性。在第0、2和4周用包含腫瘤相關抗原CEA的Ad5DE1 RhCEA(1011vp)三次注射免疫動物，隨後在第16、18和20周用CV33DE1 RhCEA(1011vp)接種。用恆河猴CEA肽通過IFN-γ ELISPOT測量T細胞反應。
結果在附圖34中報告，其提供了在不存在(DMSO)或存在恆河猴CEA C和D肽庫的孵化之後每百萬PBMC中斑點形成細胞的數目，確定了基於用兩種不同的Ad血清型的接種的免疫方案在非人靈長類中引起針對CEA的持續的T細胞反應。
雖然已經參考本發明的某些優選的實施方式詳細描述了本發明，要理解的是，修改和變化都處在所描述的和要求權利的精神和範圍之內。
序 列 表110Merck Co.，Inc.
Instituto di Ricerche di Biologia Molecolare P.Angeletti S.p.A.
120黑猩猩腺病毒疫苗載運體130ITR004 8Y PCT15060/538,7991512004-01-23160125170FastSEQ for Windows Version 4.0210121137741212DNA213黑猩猩腺病毒-ChAd3基因組4001catcatcaat aatatacctt attttggatt gaagccaata tgataatgag atgggcggcg 60cgaggcgggg cgcggggcgg gaggcgggtt tgggggcggg ccggcgggcg gggcggtgtg 120gcggaagtgg actttgtaag tgtggcggat gtgacttgct agtgccgggc gcggtaaaag 180tgacgttttc cgtgcgcgac aacgcccccg ggaagtgaca tttttcccgc ggtttttacc 240ggatgttgta gtgaatttgg gcgtaaccaa gtaagatttg gccattttcg cgggaaaact 300gaaacgggga agtgaaatct gattaatttt gcgttagtca taccgcgtaa tatttgtcta 360gggccgaggg actttggccg attacgtgga ggactcgccc aggtgttttt tgaggtgaat 420ttccgcgttc cgggtcaaag tctccgtttt attattatag tcagctgacg cggagtgtat 480ttataccctc tgatctcgtc aagaggccac tcttgagtgc cagcgagtag agttttctcc 540tctgccgctc tccgctccgc tccgctcggc tctgacaccg gggaaaaaat gagacatttc 600acctacgatg gcggtgtgct caccggccag ctggctgctg aggtcctgga caccctgatc 660gaggaggtat tggccgataa ttatcctccc tcgactcctt ttgagccacc tacacttcac 720
gaactatacg atctggatgt ggtggggccc agcgatccga acgagcaggc ggtttccagt 780ttttttccag agtccatgtt gttggccagc caggaggggg tcgaacttga gacccctcct 840ccgatcgtgg attcccccga tccgccgcag ctgactaggc agcccgagcg ctgtgcggga 900cctgagacta tgccccagct gctacctgag gtgatcgatc tcacctgtaa tgagtctggt 960tttccaccca gcgaggatga ggacgaagag ggtgagcagt ttgtgttaga ttctgtggaa 1020caacccgggc gaggatgcag gtcttgtcaa tatcaccgga aaaacacagg agactcccag 1080attatgtgtt ctctgtgtta tatgaagatg acctgtatgt ttatttacag taagtttatc 1140atcggtgggc aggtgggcta tagtgtgggt ggtggtcttt ggggggtttt ttaatatatg 1200tcaggggtta tgctgaagac ttttttattg tgatttttaa aggtccagtg tctgagcccg 1260agcaagaacc tgaaccggag cctgagcctt ctcgccccag gagaaagcct gtaatcttaa 1320ctagacccag cgcaccggta gcgagaggcc tcagcagcgc ggagaccacc gactccggtg 1380cttcctcatc acccccggag attcaccccc tggtgcccct atgtcccgtt aagcccgttg 1440ccgtgagagt cagtgggcgg cggtctgctg tggagtgcat tgaggacttg ctttttgatt 1500cacaggaacc tttggacttg agcttgaaac gccccaggca ttaaacctgg tcacctggac 1560tgaatgagtt gacgcctatg tttgcttttg aatgacttaa tgtgtataga taataaagag 1620tgagataatg ttttaattgc atggtgtgtt taacttgggc ggagtctgct gggtatataa 1680gcttccctgg gctaaacttg gttacacttg acctcatgga ggcctgggag tgtttggaga 1740actttgccgg agttcgtgcc ttgctggacg agagctctaa caatacctct tggtggtgga 1800ggtatttgtg gggctctccc cagggcaagt tagtttgtag aatcaaggag gattacaagt 1860gggaatttga agagcttttg aaatcctgtg gtgagctatt ggattctttg aatctaggcc 1920accaggctct cttccaggag aaggtcatca ggactttgga tttttccaca ccggggcgca 1980ttgcagccgc ggttgctttt ctagcttttt tgaaggatag atggagcgaa gagacccact 2040tgagttcggg ctacgtcctg gattttctgg ccatgcaact gtggagagca tggatcagac 2100acaagaacag gctgcaactg ttgtcttccg tccgcccgtt gctgattccg gcggaggagc 2160aacaggccgg gtcagaggac cgggcccgtc gggatccgga ggagagggca ccgaggccgg 2220gcgagaggag cgcgctgaac ctgggaaccg ggctgagcgg ccatccacat cgggagtgaa 2280tgtcgggcag gtggtggatc tttttccaga actgcggcgg attttgacta ttagggagga 2340tgggcaattt gttaagggtc ttaagaggga gaggggggct tctgagcata acgaggaggc 2400cagtaattta gcttttagct tgatgaccag acaccgtcca gagtgcatca cttttcagca 2460gattaaggac aattgtgcca atgagttgga tctgttgggt cagaagtata gcatagagca 2520gctgaccact tactggctgc agccgggtga tgatctggag gaagctatta gggtgtatgc 2580taaggtggcc ctgcggcccg attgcaagta caagctcaag gggctggtga atatcaggaa 2640ttgttgctac atttctggca acggggcgga ggtggagata gagaccgaag acagggtggc 2700tttcagatgc agcatgatga atatgtggcc gggggtgctg ggcatggacg gggtggtgat 2760tatgaatgtg aggttcacgg ggcccaactt taacggcacg gtgtttttgg ggaacaccaa 2820
cctggtcctg cacggggtga gcttctatgg gtttaacaac acctgtgtgg aggcctggac 2880cgatgtgaag gtccgcggtt gcgcctttta tggatgttgg aaggccatag tgagccgccc 2940taagagcagg agttccatta agaaatgctt gtttgagagg tgcaccttgg ggatcctggc 3000cgagggcaac tgcagggtgc gccacaatgt ggcctccgag tgcggttgct tcatgctagt 3060caagagcgtg gcggtaatca agcataatat ggtgtgcggc aacagcgagg acaaggcctc 3120acagatgctg acctgcacgg atggcaactg ccacttgctg aagaccatcc atgtaaccag 3180ccacagccgg aaggcctggc ccgtgttcga gcacaacttg ctgacccgct gctccttgca 3240tctgggcaac aggcgggggg tgttcctgcc ctatcaatgc aactttagtc acaccaagat 3300cttgctagag cccgagagca tgtccaaggt gaacttgaac ggggtgtttg acatgaccat 3360gaagatctgg aaggtgctga ggtacgacga gaccaggtcc cggtgcagac cctgcgagtg 3420cgggggcaag catatgagga accagcccgt gatgctggat gtgaccgagg agctgaggac 3480agaccacttg gttctggcct gcaccagggc cgagtttggt tctagcgatg aagacacaga 3540ttgaggtggg tgagtgggcg tggcctgggg tggtcatgaa aatatataag ttgggggtct 3600tagggtctct ttatttgtgt tgcagagacc gccggagcca tgagcgggag cagcagcagc 3660agcagtagca gcagcgcctt ggatggcagc atcgtgagcc cttatttgac gacgcggatg 3720ccccactggg ccggggtgcg tcagaatgtg atgggctcca gcatcgacgg ccgacccgtc 3780ctgcccgcaa attccgccac gctgacctat gcgaccgtcg cggggacgcc gttggacgcc 3840accgccgccg ccgccgccac cgcagccgcc tcggccgtgc gcagcctggc cacggacttt 3900gcattcctgg gaccactggc gacaggggct acttctcggg ccgctgctgc cgccgttcgc 3960gatgacaagc tgaccgccct gctggcgcag ttggatgcgc ttactcggga actgggtgac 4020ctttctcagc aggtcatggc cctgcgccag caggtctcct ccctgcaagc tggcgggaat 4080gcttctccca caaatgccgt ttaagataaa taaaaccaga ctctgtttgg attaaagaaa 4140agtagcaagt gcattgctct ctttatttca taattttccg cgcgcgatag gccctagacc 4200agcgttctcg gtcgttgagg gtgcggtgta tcttctccag gacgtggtag aggtggctct 4260ggacgttgag atacatgggc atgagcccgt cccgggggtg gaggtagcac cactgcagag 4320cttcatgctc cggggtggtg ttgtagatga tccagtcgta gcaggagcgc tgggcatggt 4380gcctaaaaat gtccttcagc agcaggccga tggccagggg gaggcccttg gtgtaagtgt 4440ttacaaaacg gttaagttgg gaagggtgca ttcggggaga gatgatgtgc atcttggact 4500gtatttttag attggcgatg tttccgccca gatcccttct gggattcatg ttgtgcagga 4560ccaccagtac agtgtatccg gtgcacttgg ggaatttgtc atgcagctta gagggaaaag 4620cgtggaagaa cttggagacg cccttgtggc ctcccagatt ttccatgcat tcgtccatga 4680tgatggcaat gggcccgcgg gaggcagctt gggcaaagat atttctgggg tcgctgacgt 4740cgtagttgtg ttccagggtg aggtcgtcat aggccatttt tacaaagcgc gggcggaggg 4800tgcccgactg ggggatgatg gtcccctctg gccctggggc gtagttgccc tcgcagatct 4860gcatttccca ggccttaatc tcggaggggg gaatcatatc cacctgcggg gcgatgaaga 4920
aaacggtttc cggagccggg gagattaact gggatgagag caggtttcta agcagctgtg 4980attttccaca accggtgggc ccataaataa cacctataac cggttgcagc tggtagttta 5040gagagctgca gctgccgtcg tcccggagga ggggggccac ctcgttgagc atgtccctga 5100cgcgcatgtt ctccccgacc agatccgcca gaaggcgctc gccgcccagg gacagcagct 5160cttgcaagga agcaaagttt ttcagcggct tgaggccgtc cgccgtgggc atgtttttca 5220gggtctggct cagcagctcc aggcggtccc agagctcggt gacgtgctct acggcatctc 5280tatccagcat atctcctcgt ttcgcgggtt ggggcgactt tcgctgtagg gcaccaagcg 5340gtggtcgtcc agcggggcca aagtcatgtc cttccatggg cgcagggtcc tcgtcagggt 5400ggtctgggtc acggtgaagg ggtgcgctcc gggctgagcg cttgccaagg tgcgcttgag 5460gctggttctg ctggtgctga agcgctgccg gtcttcgccc tgcgcgtcgg ccaggtagca 5520tttgaccatg gtgtcatagt ccagcccctc cgcggcgtgt cccttggcgc gcagcttgcc 5580cttggaggtg gcgccgcacg aggggcagag caggctcttg agcgcgtaga gcttgggggc 5640gaggaagacc gattcggggg agtaggcgtc cgcgccgcag accccgcaca cggtctcgca 5700ctccaccagc caggtgagct cggggcgcgc cgggtcaaaa accaggtttc ccccatgctt 5760tttgatgcgt ttcttacctc gggtctccat gaggtggtgt ccccgctcgg tgacgaagag 5820gctgtccgtg tctccgtaga ccgacttgag gggtcttttc tccagggggg tccctcggtc 5880ttcctcgtag aggaactcgg accactctga gacgaaggcc cgcgtccagg ccaggacgaa 5940ggaggctatg tgggaggggt agcggtcgtt gtccactagg gggtccacct tctccaaggt 6000gtgaagacac atgtcgcctt cctcggcgtc caggaaggtg attggcttgt aggtgtaggc 6060cacgtgaccg ggggttcctg acgggggggt ataaaagggg gtgggggcgc gctcgtcgtc 6120actctcttcc gcatcgctgt ctgcgagggc cagctgctgg ggtgagtatt ccctctcgaa 6180ggcgggcatg acctccgcgc tgaggttgtc agtttccaaa aacgaggagg atttgatgtt 6240cacctgtccc gaggtgatac ctttgagggt acccgcgtcc atctggtcag aaaacacgat 6300ctttttattg tccagcttgg tggcgaacga cccgtagagg gcgttggaga gcagcttggc 6360gatggagcgc agggtctggt tcttgtccct gtcggcgcgc tccttggccg cgatgttgag 6420ctgcacgtac tcgcgcgcga cgcagcgcca ctcggggaag acggtggtgc gctcgtcggg 6480caccaggcgc acgcgccagc cgcggttgtg cagggtgacc aggtccacgc tggtggcgac 6540ctcgccgcgc aggcgctcgt tggtccagca gagacggccg cccttgcgcg agcagaaggg 6600gggcaggggg tcgagctggg tctcgtccgg ggggtccgcg tccacggtga aaaccccggg 6660gcgcaggcgc gcgtcgaagt agtctatctt gcaaccttgc atgtccagcg cctgctgcca 6720gtcgcgggcg gcgagcgcgc gctcgtaggg gttgagcggc gggccccagg gcatggggtg 6780ggtgagtgcg gaggcgtaca tgccgcagat gtcatagacg tagaggggct cccgcaggac 6840cccgatgtag gtggggtagc agcggccgcc gcggatgctg gcgcgcacgt agtcatacag 6900ctcgtgcgag ggggcgagga ggtcggggcc caggttggtg cgggcggggc gctccgcgcg 6960gaagacgatc tgcctgaaga tggcatgcga gttggaagag atggtggggc gctggaagac 7020
gttgaagctg gcgtcctgca ggccgacggc gtcgcgcacg aaggaggcgt aggagtcgcg 7080cagcttgtgt accagctcgg cggtgacctg cacgtcgagc gcgcagtagt cgagggtctc 7140gcggatgatg tcatatttag cctgcccctt ctttttccac agctcgcggt tgaggacaaa 7200ctcttcgcgg tctttccagt actcttggat cgggaaaccg tccggttccg aacggtaaga 7260gcctagcatg tagaactggt tgacggcctg gtaggcgcag cagcccttct ccacggggag 7320ggcgtaggcc tgcgcggcct tgcggagcga ggtgtgggtc agggcgaagg tgtccctgac 7380catgactttg aggtactggt gcttgaagtc ggagtcgtcg cagccgcccc gctcccagag 7440cgagaagtcg gtgcgcttct tggagcgggg gttgggcaga gcgaaggtga catcgttgaa 7500gaggattttg cccgcgcggg gcatgaagtt gcgggtgatg cggaagggcc ccggcacttc 7560agagcggttg ttgatgacct gggcggcgag cacgatctcg tcgaagccgt tgatgttgtg 7620gcccacgatg tagagttcca ggaagcgggg ccggcccttt acggtgggca gcttctttag 7680ctcttcgtag gtgagctcct cgggcgaggc gaggccgtgc tcggccaggg cccagtccgc 7740gaggtgcggg ttgtctctga ggaaggactc ccagaggtcg cgggccagga gggtctgcag 7800gcggtccctg aaggtcctga actggcggcc cacggccatt ttttcggggg tgatgcagta 7860gaaggtgagg gggtcttgct gccagcggtc ccagtcgagc tgcagggcga ggtcgcgcgc 7920ggcggtgacc aggcgctcgt cgcccccgaa tttcatgacc agcatgaagg gcacgagctg 7980ctttccgaag gcccccatcc aagtgtaggt ctctacatcg taggtgacaa agaggcgctc 8040cgtgcgagga tgcgagccga tcgggaagaa ctggatctcc cgccaccagt tggaggagtg 8100gctgttgatg tggtggaagt agaagtcccg tcgccgggcc gaacactcgt gctggctttt 8160gtaaaagcga gcgcagtact ggcagcgctg cacgggctgt acctcctgca cgagatgcac 8220ctttcgcccg cgcacgagga agccgagggg aaatctgagc cccccgcctg gctcgcggca 8280tggctggtgc tcttctactt tggatgcgtg tccgtctccg tctggctcct cgaggggtgt 8340tacggtggag cggaccacca cgccgcgcga gccgcaggtc cagatatcgg cgcgcggcgg 8400tcggagtttg atgacgacat cgcgcagctg ggagctgtcc atggtctgga gctcccgcgg 8460cggcggcagg tcagccggga gttcttgcag gttcacctcg cagagtcggg ccagggcgcg 8520gggcaggtct aggtggtacc tgatctctag gggcgtgttg gtggcggcgt cgatggcttg 8580caggagcccg catccccggg gggcgacgac ggtgccccgc ggggtggtgg tggtggtggt 8640ggtggtggtg gtggcggtgc agctcagaag cggtgccgcg ggcgggcccc cggaggtagg 8700gggggctccg gtcccgccgg caggggcggc agcggcacgt cggcgtggag cgcgggcagg 8760agttggtgct gtgcccggag gttgctggcg aaggcgacga cgcggcggtt gatctcctgg 8820atctggcgcc tctgcgtgaa gacgacgggc ccggtgagct tgaacctgaa agagagttcg 8880acagaatcaa tctcggtgtc attgaccgcg gcctggcgca ggatctcctg cacgtctccc 8940gagttgtctt ggtaggcgat ctcggccatg aactgctcga tctcttcctc ctggaggtct 9000ccgcgtccgg cgcgttccac ggtggccgcc aggtcgttgg agatgcgccc catgagctgc 9060gagaaggcgt tgagtccgcc ctcgttccag actcggctgt agaccacgcc cccctggtca 9120
tcgcgggcgc gcatgaccac ctgcgcgagg ttgagctcca cgtgccgcgc gaagacggcg 9180tagttgcgca gacgctggaa gaggtagttg agggtggtgg cggtgtgctc ggccacgaag 9240aagttcatga cccagcggcg caacgtggat tcgttgatgt cccccaaggc ctccagccgt 9300tccatggcct cgtagaagtc cacggcgaag ttgaaaaact gggagttgcg cgccgacacg 9360gtcaactcct cctccagaag acggatgagc tcggcgacgg tgtcgcgcac ctcgcgctcg 9420aaggctatgg ggatctcttc ctccgctagc atcaccacct cctcctcttc ctcctcttct 9480ggcacttcca tgatggcttc ctcctcttcg gggggcggcg gcggcggcgg tgggggaggg 9540ggcgctctgc gccggcggcg gcgcaccggg aggcggtcca cgaagcgcgc gatcatctcc 9600ccgcggcggc ggcgcatggt ctcggtgacg gcgcggccgt tctcccgggg gcgcagttgg 9660aagacgccgc cggacatctg gtgctggggc gggtggccgt gaggcagcga aacggcgctg 9720acgatgcatc tcaacaattg ctgcgtaggt acgccgccga gggacctgag ggagtccata 9780tccaccggat ccgaaaacct ttcgaggaag gcgtctaacc agtcgcagtc gcaaggtagg 9840ctgagcaccg tggcgggcgg cggggggtgg ggggagtgtc tggcggaggt gctgctgatg 9900atgtaattga agtaggcgga cttgacacgg cggatggtcg acaggagcac catgtccttg 9960ggtccggcct gctggatgcg gaggcggtcg gctatgcccc aggcttcgtt ctggcatcgg 10020cgcaggtcct tgtagtagtc ttgcatgagc ctttccaccg gcacctcttc tccttcctct 10080tctgcttctt ccatgtctgc ttcggccctg gggcggcgcc gcgcccccct gccccccatg 10140cgcgtgaccc cgaaccccct gagcggttgg agcagggcca ggtcggcgac gacgcgctcg 10200gccaggatgg cctgctgcac ctgcgtgagg gtggtttgga agtcatccaa gtccacgaag 10260cggtggtagg cgcccgtgtt gatggtgtag gtgcagttgg ccatgacgga ccagttgacg 10320gtctggtggc ccggttgcga catctcggtg tacctgagtc gcgagtaggc gcgggagtcg 10380aagacgtagt cgttgcaagt ccgcaccagg tactggtagc ccaccaggaa gtgcggcggc 10440ggctggcggt agaggggcca gcgcagggtg gcgggggctc cgggggccag gtcttccagc 10500atgaggcggt ggtaggcgta gatgtacctg gacatccagg tgatacccgc ggcggtggtg 10560gaggcgcgcg ggaagtcgcg cacccggttc cagatgttgc gcaggggcag aaagtgctcc 10620atggtaggcg tgctctgtcc agtcagacgc gcgcagtcgt tgatactcta gaccagggaa 10680aacgaaagcc ggtcagcggg cactcttccg tggtctggtg aatagatcgc aagggtatca 10740tggcggaggg cctcggttcg agccccgggt ccgggccgga cggtccgcca tgatccacgc 10800ggttaccgcc cgcgtgtcga acccaggtgt gcgacgtcag acaacggtgg agtgttcctt 10860ttggcgtttt tctggccggg cgccggcgtc gcgtaagaga ctaagccgcg aaagcgaaag 10920cagtaagtgg ctcgctcccc gtagccggag ggatccttgc taagggttgc gttgcggcga 10980accccggttc gaatcccgta ctcgggccgg ccggacccgc ggctaaggtg ttggattggc 11040ctccccctcg tataaagacc ccgcttgcgg attgactccg gacacgggga cgagcccctt 11100ttatttttgc tttccccaga tgcatccggt gctgcggcag atgcgccccc cgccccagca 11160gcagcaacaa caccagcaag agcggcagca acagcagcgg gagtcatgca gggccccctc 11220
acccaccctc ggcgggccgg ccacctcggc gtccgcggcc gtgtctggcg cctgcggcgg 11280cggcgggggg ccggctgacg accccgagga gcccccgcgg cgcagggcca gacactacct 11340ggacctggag gagggcgagg gcctggcgcg gctgggggcg ccgtctcccg agcgccaccc 11400gcgggtgcag ctgaagcgcg actcgcgcga ggcgtacgtg cctcggcaga acctgttcag 11460ggaccgcgcg ggcgaggagc ccgaggagat gcgggacagg aggttcagcg cagggcggga 11520gctgcggcag gggctgaacc gcgagcggct gctgcgcgag gaggactttg agcccgacgc 11580gcggacgggg atcagccccg cgcgcgcgca cgtggcggcc gccgacctgg tgacggcgta 11640cgagcagacg gtgaaccagg agatcaactt ccaaaagagt ttcaacaacc acgtgcgcac 11700gctggtggcg cgcgaggagg tgaccatcgg gctgatgcac ctgtgggact ttgtaagcgc 11760gctggtgcag aaccccaaca gcaagcctct gacggcgcag ctgttcctga tagtgcagca 11820cagcagggac aacgaggcgt ttagggacgc gctgctgaac atcaccgagc ccgagggtcg 11880gtggctgctg gacctgatta acatcctgca gagcatagtg gtgcaggagc gcagcctgag 11940cctggccgac aaggtggcgg ccatcaacta ctcgatgctg agcctgggca agttttacgc 12000gcgcaagatc taccagacgc cgtacgtgcc catagacaag gaggtgaaga tcgacggttt 12060ttacatgcgc atggcgctga aggtgctcac cctgagcgac gacctgggcg tgtaccgcaa 12120cgagcgcatc cacaaggccg tgagcgtgag ccggcggcgc gagctgagcg accgcgagct 12180gatgcacagc ctgcagcggg cgctggcggg cgccggcagc ggcgacaggg aggcggagtc 12240ctacttcgat gcgggggcgg acctgcgctg ggcgcccagc cggcgggccc tggaggccgc 12300gggggtccgc gaggactatg acgaggacgg cgaggaggat gaggagtacg agctagagga 12360gggcgagtac ctggactaaa ccgcgggtgg tgtttccggt agatgcaaga cccgaacgtg 12420gtggacccgg cgctgcgggc ggctctgcag agccagccgt ccggccttaa ctcctcagac 12480gactggcgac aggtcatgga ccgcatcatg tcgctgacgg cgcgtaaccc ggacgcgttc 12540cggcagcagc cgcaggccaa caggctctcc gccatcctgg aggcggtggt gcctgcgcgc 12600tcgaacccca cgcacgagaa ggtgctggcc atagtgaacg cgctggccga gaacagggcc 12660atccgcccgg acgaggccgg gctggtgtac gacgcgctgc tgcagcgcgt ggcccgctac 12720aacagcggca acgtgcagac caacctggac cggctggtgg gggacgtgcg cgaggcggtg 12780gcgcagcgcg agcgcgcgga tcggcagggc aacctgggct ccatggtggc gctgaatgcc 12840ttcctgagca cgcagccggc caacgtgccg cgggggcagg aagactacac caactttgtg 12900agcgcgctgc ggctgatggt gaccgagacc ccccagagcg aggtgtacca gtcgggcccg 12960gactacttct tccagaccag cagacagggc ctgcagacgg tgaacctgag ccaggctttc 13020aagaacctgc gggggctgtg gggcgtgaag gcgcccaccg gcgaccgggc gacggtgtcc 13080agcctgctga cgcccaactc gcgcctgctg ctgctgctga tcgcgccgtt cacggacagc 13140ggcagcgtgt cccgggacac ctacctgggg cacctgctga ccctgtaccg cgaggccatc 13200gggcaggcgc aggtggacga gcacaccttc caggagatca ccagcgtgag ccgcgcgctg 13260gggcaggagg acacgagcag cctggaggcg actctgaact acctgctgac caaccggcgg 13320
cagaagattc cctcgctgca cagcctgacc tccgaggagg agcgcatctt gcgctacgtg 13380cagcagagcg tgagcctgaa cctgatgcgc gacggggtga cgcccagcgt ggcgctggac 13440atgaccgcgc gcaacatgga accgggcatg tacgccgcgc accggcctta catcaaccgc 13500ctgatggact acctgcatcg cgcggcggcc gtgaaccccg agtactttac caacgccatc 13560ctgaacccgc actggctccc gccgcccggg ttctacagcg ggggcttcga ggtcccggag 13620gccaacgatg gcttcctgtg ggacgacatg gacgacagcg tgttctcccc gcggccgcag 13680gcgctggcgg aagcgtccct gctgcgtccc aagaaggagg aggaggaggc gagtcgccgc 13740cgcggcagca gcggcgtggc ttctctgtcc gagctggggg cggcagccgc cgcgcgcccc 13800gggtccctgg gcggcagccc ctttccgagc ctggtggggt ctctgcacag cgagcgcacc 13860acccgccctc ggctgctggg cgaggacgag tacctgaata actccctgct gcagccggtg 13920cgggagaaaa acctgccccc cgccttcccc aacaacggga tagagagcct ggtggacaag 13980atgagcagat ggaagaccta tgcgcaggag cacagggacg cgcccgcgct ccggccgccc 14040acgcggcgcc agcgccacga ccggcagcgg gggctggtgt gggatgacga ggactccgcg 14100gacgatagca gcgtgctgga cctgggaggg agcggcaacc cgttcgcgca cctgcgcccc 14160cgcctgggga ggatgtttta aaaaaaaaaa aagcaagaag catgatgcaa aattaaataa 14220aactcaccaa ggccatggcg accgagcgtt ggtttcttgt gttcccttca gtatgcggcg 14280cgcggcgatg taccaggagg gacctcctcc ctcttacgag agcgtggtgg gcgcggcggc 14340ggcggcgccc tcttctccct ttgcgtcgca gctgctggag ccgccgtacg tgcctccgcg 14400ctacctgcgg cctacggggg ggagaaacag catccgttac tcggagctgg cgcccctgtt 14460cgacaccacc cgggtgtacc tggtggacaa caagtcggcg gacgtggcct ccctgaacta 14520ccagaacgac cacagcaatt ttttgaccac ggtcatccag aacaatgact acagcccgag 14580cgaggccagc acccagacca tcaatctgga tgaccggtcg cactggggcg gcgacctgaa 14640aaccatcctg cacaccaaca tgcccaacgt gaacgagttc atgttcacca ataagttcaa 14700ggcgcgggtg atggtgtcgc gctcgcacac caaggaagac cgggtggagc tgaagtacga 14760gtgggtggag ttcgagctgc cagagggcaa ctactccgag accatgacca ttgacctgat 14820gaacaacgcg atcgtggagc actatctgaa agtgggcagg caaaacgggg tcctggagag 14880cgacatcggg gtcaagttcg acaccaggaa cttccgcctg gggctggacc ccgtgaccgg 14940gctggttatg cccggggtgt acaccaacga ggccttccat cccgacatca tcctgctgcc 15000cggctgcggg gtggacttca cttacagccg cctgagcaac ctcctgggca tccgcaagcg 15060gcagcccttc caggagggct tcaggatcac ctacgaggac ctggaggggg gcaacatccc 15120cgcgctcctc gatgtggagg cctaccagga tagcttgaag gaaaatgagg cgggacagga 15180ggataccacc cccgccgcct ccgccgccgc cgagcagggc gaggatgctg ctgacaccgc 15240ggccgcggac ggggcagagg ccgaccccgc tatggtggtg gaggctcccg agcaggagga 15300ggatatgaat gacagtgcgg tgcgcggaga caccttcgtc acccgggggg aggaaaagca 15360agcggaggcc gaggccgcgg ccgaggaaaa gcaactggcg gcagcagcgg cggcggcggc 15420
gttggccgcg gcggaggctg agtctgaggg gaccaagccc gccaaggagc ccgtgattaa 15480gcccctgacc gaagatagca agaagcgcag ttacaacctg ctcaaggaca gcaccaacac 15540cgcgtaccgc agctggtacc tggcctacaa ctacggcgac ccgtcgacgg gggtgcgctc 15600ctggaccctg ctgtgcacgc cggacgtgac ctgcggctcg gagcaggtgt actggtcgct 15660gcccgacatg atgcaagacc ccgtgacctt ccgctccacg cggcaggtca gcaacttccc 15720ggtggtgggc gccgagctgc tgcccgtgca ctccaagagc ttctacaacg accaggccgt 15780ctactcccag ctcatccgcc agttcacctc tctgacccac gtgttcaatc gctttcctga 15840gaaccagatt ctggcgcgcc cgcccgcccc caccatcacc accgtcagtg aaaacgttcc 15900tgctctcaca gatcacggga cgctaccgct gcgcaacagc atcggaggag tccagcgagt 15960gaccgttact gacgccagac gccgcacctg cccctacgtt tacaaggcct tgggcatagt 16020ctcgccgcgc gtcctttcca gccgcacttt ttgagcaaca ccaccatcat gtccatcctg 16080atctcaccca gcaataactc cggctgggga ctgctgcgcg cgcccagcaa gatgttcgga 16140ggggcgagga agcgttccga gcagcacccc gtgcgcgtgc gcgggcactt ccgcgccccc 16200tggggagcgc acaaacgcgg ccgcgcgggg cgcaccaccg tggacgacgc catcgactcg 16260gtggtggagc aggcgcgcaa ctacaggccc gcggtctcta ccgtggacgc ggccatccag 16320accgtggtgc ggggcgcgcg gcggtacgcc aagctgaaga gccgccggaa gcgcgtggcc 16380cgccgccacc gccgccgacc cggggccgcc gccaaacgcg ccgccgcggc cctgcttcgc 16440cgggccaagc gcacgggccg ccgcgccgcc atgagggccg cgcgccgctt ggccgccggc 16500atcaccgccg ccaccatggc cccccgtacc cgaagacgcg cggccgccgc cgccgccgcc 16560gccatcagtg acatggccag caggcgccgg ggcaacgtgt actgggtgcg cgactcggtg 16620accggcacgc gcgtgcccgt gcgcttccgc cccccgcgga cttgagatga tgtgaaaaaa 16680caacactgag tctcctgctg ttgtgtgtat cccagcggcg gcggcgcgcg cagcgtcatg 16740tccaagcgca aaatcaaaga agagatgctc caggtcgtcg cgccggagat ctatgggccc 16800ccgaagaagg aagagcagga ttcgaagccc cgcaagataa agcgggtcaa aaagaaaaag 16860aaagatgatg acgatgccga tggggaggtg gagttcctgc gcgccacggc gcccaggcgc 16920ccggtgcagt ggaagggccg gcgcgtaaag cgcgtcctgc gccccggcac cgcggtggtc 16980ttcacgcccg gcgagcgctc cacccggact ttcaagcgcg tctatgacga ggtgtacggc 17040gacgaagacc tgctggagca ggccaacgag cgcttcggag agtttgctta cgggaagcgt 17100cagcgggcgc tggggaagga ggacctgctg gcgctgccgc tggaccaggg caaccccacc 17160cccagtctga agcccgtgac cctgcagcag gtgctgccga gcagcgcacc ctccgaggcg 17220aagcggggtc tgaagcgcga gggcggcgac ctggcgccca ccgtgcagct catggtgccc 17280aagcggcaga ggctggagga tgtgctggag aaaatgaaag tagaccccgg tctgcagccg 17340gacatcaggg tccgtcccat caagcaggtg gcgccgggcc tcggcgtgca gaccgtggac 17400gtggtcatcc ccaccggcaa ctcccccgcc gccaccacca ctaccgctgc ctccacggac 17460atggagacac agaccgatcc cgccgcagcc gcagccgccg ccgcagccgc gacctcctcg 17520
gcggaggtgc agacggaccc ctggctgccg ccggcgatgt cagctccccg cgcgcgccgc 17580ggacgcagaa agtacggcgc cgccaacgcg ctcctgcccg agtacgcctt gcatccttcc 17640atcgcgccca cccccggcta ccgaggctat acctaccgcc cgcgaagagc caagggttcc 17700acccgccgtc cccgccgacg cgccgccgcc accacccgcc gccgccgccg cagacgccag 17760cccgcactgg ctccagtctc cgtgaggaga gtggcgcgcg acggacacac cctggtgctg 17820cccagggcgc gctaccaccc cagcatcgtt taaaagcctg ttgtggttct tgcagatatg 17880gccctcactt gccgcctccg tttcccggtg ccgggatacc gaggaggaag atcgcgccgc 17940aggaggggtc tggccggccg cggcctgagc ggaggcagcc gccgcgcgca ccggcggcga 18000cgcgccacca gccgacgcat gcgcggcggg gtgctgcccc tgttaatccc cctgatcgcc 18060gcggcgatcg gcgccgtgcc cgggatcgcc tccgtggcct tgcaagcgtc ccagaggcat 18120tgacagactt gcaaacttgc aaatatggaa aaaaaaaaaa aaccccaata aaaagtctag 18180actctcacgc tcgcttggtc ctgtgactat tttgtagaat ggaagacatc aactttgcgt 18240cgctggcccc gcgtcacggc tcgcgcccgt tcctgggaca ctggaacgat atcggcacca 18300gcaacatgag cggtggcgcc ttcagttggg gctctctgtg gagcggcatt aaaagtatcg 18360ggtctgccgt taaaaattac ggctcccggg cctggaacag cagcacgggc cagatgttga 18420gagacaagtt gaaagagcag aacttccagc agaaggtggt ggagggcctg gcctccggca 18480tcaacggggt ggtggacctg gccaaccagg ccgtgcagaa taaaatcaac agcagactgg 18540acccccggcc gccggtggag gaggtgccgc cggcgctgga gacggtgtcc cccgatgggc 18600gtggcgagaa gcgcccgcgg cccgataggg aagagaccac tctggtcacg cagaccgatg 18660agccgccccc gtatgaggag gccctaaagc aaggtctgcc caccacgcgg cccatcgcgc 18720ccatggccac cggggtggtg ggccgccaca cccccgccac gctggacttg cctccgcccg 18780ccgatgtgcc gcagcagcag aaggcggcac agccgggccc gcccgcgacc gcctcccgtt 18840cctccgccgg tcctctgcgc cgcgcggcca gcggcccccg cgggggggtc gcgaggcacg 18900gcaactggca gagcacgctg aacagcatcg tgggtctggg ggtgcggtcc gtgaagcgcc 18960gccgatgcta ctgaatagct tagctaacgt gttgtatgtg tgtatgcgcc ctatgtcgcc 19020gccagaggag ctgctgagtc gccgccgttc gcgcgcccac caccaccgcc actccgcccc 19080tcaagatggc gaccccatcg atgatgccgc agtggtcgta catgcacatc tcgggccagg 19140acgcctcgga gtacctgagc cccgggctgg tgcagttcgc ccgcgccacc gagagctact 19200tcagcctgag taacaagttt aggaacccca cggtggcgcc cacgcacgat gtgaccaccg 19260accggtctca gcgcctgacg ctgcggttca ttcccgtgga ccgcgaggac accgcgtact 19320cgtacaaggc gcggttcacc ctggccgtgg gcgacaaccg cgtgctggac atggcctcca 19380cctactttga catccgcggg gtgctggacc ggggtcccac tttcaagccc tactctggca 19440ccgcctacaa ctccctggcc cccaagggcg ctcccaactc ctgcgagtgg gagcaagagg 19500aaactcaggc agttgaagaa gcagcagaag aggaagaaga agatgctgac ggtcaagctg 19560aggaagagca agcagctacc aaaaagactc atgtatatgc tcaggctccc ctttctggcg 19620
aaaaaattag taaagatggt ctgcaaatag gaacggacgc tacagctaca gaacaaaaac 19680ctatttatgc agaccctaca ttccagcccg aaccccaaat cggggagtcc cagtggaatg 19740aggcagatgc tacagtcgcc ggcggtagag tgctaaagaa atctactccc atgaaaccat 19800gctatggttc ctatgcaaga cccacaaatg ctaatggagg tcagggtgta ctaacggcaa 19860atgcccaggg acagctagaa tctcaggttg aaatgcaatt cttttcaact tctgaaaacg 19920cccgtaacga ggctaacaac attcagccca aattggtgct gtatagtgag gatgtgcaca 19980tggagacccc ggatacgcac ctttcttaca agcccgcaaa aagcgatgac aattcaaaaa 20040tcatgctggg tcagcagtcc atgcccaaca gacctaatta catcggcttc agagacaact 20100ttatcggcct catgtattac aatagcactg gcaacatggg agtgcttgca ggtcaggcct 20160ctcagttgaa tgcagtggtg gacttgcaag acagaaacac agaactgtcc taccagctct 20220tgcttgattc catgggtgac agaaccagat acttttccat gtggaatcag gcagtggaca 20280gttatgaccc agatgttaga attattgaaa atcatggaac tgaagacgag ctccccaact 20340attgtttccc tctgggtggc ataggggtaa ctgacactta ccaggctgtt aaaaccaaca 20400atggcaataa cgggggccag gtgacttgga caaaagatga aacttttgca gatcgcaatg 20460aaataggggt gggaaacaat ttcgctatgg agatcaacct cagtgccaac ctgtggagaa 20520acttcctgta ctccaacgtg gcgctgtacc taccagacaa gcttaagtac aacccctcca 20580atgtggacat ctctgacaac cccaacacct acgattacat gaacaagcga gtggtggccc 20640cggggctggt ggactgctac atcaacctgg gcgcgcgctg gtcgctggac tacatggaca 20700acgtcaaccc cttcaaccac caccgcaatg cgggcctgcg ctaccgctcc atgctcctgg 20760gcaacgggcg ctacgtgccc ttccacatcc aggtgcccca gaagttcttt gccatcaaga 20820acctcctcct cctgccgggc tcctacacct acgagtggaa cttcaggaag gatgtcaaca 20880tggtcctcca gagctctctg ggtaacgatc tcagggtgga cggggccagc atcaagttcg 20940agagcatctg cctctacgcc accttcttcc ccatggccca caacacggcc tccacgctcg 21000aggccatgct caggaacgac accaacgacc agtccttcaa tgactacctt tccgccgcca 21060acatgctcta ccccataccc gccaacgcca ccaacgtccc catctccatc ccctcgcgca 21120actgggcggc cttccgcggc tgggccttca cccgcctcaa gaccaaggag accccctccc 21180tgggctcggg attcgacccc tactacacct actcgggctc tattccctac ctggacggca 21240ccttctacct caaccacact ttcaagaagg tctcggtcac cttcgactcc tcggtcagct 21300ggccgggcaa cgaccgtctg ctcaccccca acgagttcga gatcaagcgc tcggtcgacg 21360gggaaggcta caacgtggcc cagtgcaaca tgaccaagga ctggttcctg gtccagatgc 21420tggccaacta caacatcggc taccagggct tctacatccc agagagctac aaggacagga 21480tgtactcctt cttcaggaac ttccagccca tgagccggca ggtggtggac cagaccaagt 21540acaaggacta ccaggaggtg ggcatcatcc accagcacaa caactcgggc ttcgtgggct 21600acctcgcccc caccatgcgc gagggacagg cctaccccgc caacttcccc tacccgctca 21660taggcaagac cgcggtcgac agcatcaccc agaaaaagtt cctctgcgac cgcaccctct 21720
ggcgcatccc cttctccagc aacttcatgt ccatgggtgc gctctcggac ctgggccaga 21780acttgctcta cgccaactcc gcccacgccc tcgacatgac cttcgaggtc gaccccatgg 21840acgagcccac ccttctctat gttctgttcg aagtctttga cgtggtccgg gtccaccagc 21900cgcaccgcgg cgtcatcgag accgtgtacc tgcgtacgcc cttctcggcc ggcaacgcca 21960ccacctaaag aagcaagccg cagtcatcgc cgcctgcatg ccgtcgggtt ccaccgagca 22020agagctcagg gccatcgtca gagacctggg atgcgggccc tattttttgg gcaccttcga 22080caagcgcttc cctggctttg tctccccaca caagctggcc tgcgccatcg tcaacacggc 22140cggccgcgag accgggggcg tgcactggct ggcctttgcc tggaacccgc gctccaaaac 22200atgcttcctc tttgacccct tcggcttttc ggaccagcgg ctcaagcaaa tctacgagtt 22260cgagtacgag ggcttgctgc gtcgcagcgc catcgcctcc tcgcccgacc gctgcgtcac 22320cctcgaaaag tccacccaga ccgtgcaggg gcccgactcg gccgcctgcg gtctcttctg 22380ctgcatgttt ctgcacgcct ttgtgcactg gcctcagagt cccatggacc gcaaccccac 22440catgaacttg ctgacggggg tgcccaactc catgctccaa agcccccagg tcgagcccac 22500cctgcgccgc aaccaggagc agctctacag cttcctggag cgccactcgc cctacttccg 22560ccgccacagc gcacagatca ggagggccac ctccttctgc cacttgcaag agatgcaaga 22620agggtaataa cgatgtacac acttttttct caataaatgg catttttttt ttatttatac 22680aagctctctg gggtattcat ttcccaccac caccacccgc cgttgtcgcc atctggctct 22740atttagaaat cgaaagggtt ctgccgggag tcgccgtgcg ccacgggcag ggacacgttg 22800cgatactggt agcgggtgcc ccacttgaac tcgggcacca ccaggcgagg cagctcgggg 22860aagttttcgc tccacaggct gcgggtcagc accagcgcgt tcatcaggtc gggcgccgag 22920atcttgaagt cgcagttggg gccgccgccc tgcgcgcgcg agttgcggta caccgggttg 22980cagcactgga acaccaacag cgccgggtgc ttcacgctgg ccagcacgct gcggtcggag 23040atcagctcgg cgtccaggtc ctccgcgttg ctcagcgcga acggggtcat cttgggcact 23100tgccgcccca ggaagggcgc gtgccccggt ttcgagttgc agtcgcagcg cagcgggatc 23160agcaggtgcc cgtgcccgga ctcggcgttg gggtacagcg cgcgcatgaa ggcctgcatc 23220tggcggaagg ccatctgggc cttggcgccc tccgagaaga acatgccgca ggacttgccc 23280gagaactggt ttgcggggca gctggcgtcg tgcaggcagc agcgcgcgtc ggtgttggcg 23340atctgcacca cgttgcgccc ccaccggttc ttcacgatct tggccttgga cgattgctcc 23400ttcagcgcgc gctgcccgtt ctcgctggtc acatccatct cgatcacatg ttccttgttc 23460accatgctgc tgccgtgcag acacttcagc tcgccctccg tctcggtgca gcggtgctgc 23520cacagcgcgc agcccgtggg ctcgaaagac ttgtaggtca cctccgcgaa ggactgcagg 23580tacccctgca aaaagcggcc catcatggtc acgaaggtct tgttgctgct gaaggtcagc 23640tgcagcccgc ggtgctcctc gttcagccag gtcttgcaca cggccgccag cgcctccacc 23700tggtcgggca gcatcttgaa gttcaccttc agctcattct ccacgtggta cttgtccatc 23760agcgtgcgcg ccgcctccat gcccttctcc caggccgaca ccagcggcag gctcacgggg 23820
ttcttcacca tcaccgtggc cgccgcctcc gccgcgcttt cgctttccgc cccgctgttc 23880tcttcctctt cctcctcttc ctcgccgccg cccactcgca gcccccgcac cacggggtcg 23940tcttcctgca ggcgctgcac cttgcgcttg ccgttgcgcc cctgcttgat gcgcacgggc 24000gggttgctga agcccaccat caccagcgcg gcctcttctt gctcgtcctc gctgtccaga 24060atgacctccg gggagggggg gttggtcatc ctcagtaccg aggcacgctt ctttttcttc 24120ctgggggcgt tcgccagctc cgcggctgcg gccgctgccg aggtcgaagg ccgagggctg 24180ggcgtgcgcg gcaccagcgc gtcttgcgag ccgtcctcgt cctcctcgga ctcgagacgg 24240aggcgggccc gcttcttcgg gggcgcgcgg ggcggcggag gcggcggcgg cgacggagac 24300ggggacgaga catcgtccag ggtgggtgga cggcgggccg cgccgcgtcc gcgctcgggg 24360gtggtttcgc gctggtcctc ttcccgactg gccatctccc actgctcctt ctcctatagg 24420cagaaagaga tcatggagtc tctcatgcga gtcgagaagg aggaggacag cctaaccgcc 24480ccctctgagc cctccaccac cgccgccacc accgccaatg ccgccgcgga cgacgcgccc 24540accgagacca ccgccagtac caccctcccc agcgacgcac ccccgctcga gaatgaagtg 24600ctgatcgagc aggacccggg ttttgtgagc ggagaggagg atgaggtgga tgagaaggag 24660aaggaggagg tcgccgcctc agtgccaaaa gaggataaaa agcaagacca ggacgacgca 24720gataaggatg agacagcagt cgggcggggg aacggaagcc atgatgctga tgacggctac 24780ctagacgtgg gagacgacgt gctgcttaag cacctgcacc gccagtgcgt catcgtctgc 24840gacgcgctgc aggagcgctg cgaagtgccc ctggacgtgg cggaggtcag ccgcgcctac 24900gagcggcacc tcttcgcgcc gcacgtgccc cccaagcgcc gggagaacgg cacctgcgag 24960cccaacccgc gtctcaactt ctacccggtc ttcgcggtac ccgaggtgct ggccacctac 25020cacatcttct tccaaaactg caagatcccc ctctcctgcc gcgctaaccg cacccgcgcc 25080gacaaaaccc tgaccctgcg gcagggcgcc cacatacctg atattgcctc tctggaggaa 25140gtgcccaaga tcttcgaggg tctcggtcgc gacgagaaac gggcggcgaa cgctctgcac 25200ggagacagcg aaaacgagag tcactcgggg gtgctggtgg agctcgaggg cgacaacgcg 25260cgcctggccg tactcaagcg cagcatagag gtcacccact ttgcctaccc ggcgctcaac 25320ctgcccccca aggtcatgag tgtggtcatg ggcgagctca tcatgcgccg cgctcagccc 25380ctggccgcgg atgcaaactt gcaagagtcc tccgaggaag gcctgcccgc ggtcagcgac 25440gagcagctag cgcgctggct ggagacccgc gaccccgcgc agctggagga gcggcgcaag 25500ctcatgatgg ccgcggtgct ggtcaccgtg gagctcgagt gtctgcagcg cttcttcgcg 25560gaccccgaga tgcagcgcaa gctcgaggag accctgcact acaccttccg ccagggctac 25620gtgcgccagg cctgcaagat ctccaacgtg gagctctgca acctggtctc ctacctgggc 25680atcctgcacg agaaccgcct cgggcagaac gtcctgcact ccaccctcaa aggggaggcg 25740cgccgcgact acatccgcga ctgcgcctac ctcttcctct gctacacctg gcagacggcc 25800atgggggtct ggcagcagtg cctggaggag cgcaacctca aggagctgga aaagctactc 25860aagcgcaccc tcagggacct ctggacgggc ttcaacgagc gctcggtggc cgccgcgctg 25920
gcggacatca tcttccccga gcgcctgctc aagaccctgc agcagggcct gcccgacttc 25980accagccaga gcatgctgca gaactttagg actttcatcc tggagcgctc gggcatcctg 26040cctgccactt gctgcgcgct gcccagcgac ttcgtgccca tcaagtacag ggagtgcccg 26100ccgccgctct ggggccactg ctacctcttc cagctggcca actacctcgc ctaccactcg 26160gacctcatgg aagacgtgag cggcgagggc ctgctcgagt gccactgccg ctgcaacctc 26220tgcacgcccc accgctctct agtctgcaac ccgcagctgc tcagcgagag tcagattatc 26280ggtaccttcg agctgcaggg tccctcgcct gacgagaagt ccgcggctcc ggggctgaaa 26340ctcactccgg ggctgtggac ttccgcctac ctacgcaaat ttgtacctga ggactaccac 26400gcccacgaga tcaggttcta cgaagaccaa tcccgcccgc ccaaggcgga gctcaccgcc 26460tgcgtcatca cccaggggca catcctgggc caattgcaag ccatcaacaa agcccgccga 26520gagttcttgc tgaaaaaggg tcggggggtg tacctggacc cccagtccgg cgaggagcta 26580aacccgctac ccccgccgcc gccccagcag cgggaccttg cttcccagga tggcacccag 26640aaagaagcag cagccgccgc cgccgcagcc atacatgctt ctggaggaag aggaggagga 26700ctgggacagt caggcagagg aggtttcgga cgaggagcag gaggagatga tggaagactg 26760ggaggaggac agcagcctag acgaggaagc ttcagaggcc gaagaggtgg cagacgcaac 26820accatcaccc tcggtcgcag ccccctcgcc ggggcccctg aaatcctccg aacccagcac 26880cagcgctata acctccgctc ctccggcgcc ggcgccaccc gcccgcagac ccaaccgtag 26940atgggacacc acaggaaccg gggtcggtaa gtccaagtgc ccgccgccgc caccgcagca 27000gcagcagcag cgccagggct accgctcgtg gcgcgggcac aagaacgcca tagtcgcctg 27060cttgcaagac tgcgggggca acatctcttt cgcccggcgc ttcctgctat tccaccacgg 27120ggtcgccttt ccccgcaatg tcctgcatta ctaccgtcat ctctacagcc cctactgcag 27180cggcgaccca gaggcggcag cggcagccac agcggcgacc accacctagg aagatatcct 27240ccgcgggcaa gacagcggca gcagcggcca ggagacccgc ggcagcagcg gcgggagcgg 27300tgggcgcact gcgcctctcg cccaacgaac ccctctcgac ccgggagctc agacacagga 27360tcttccccac tttgtatgcc atcttccaac agagcagagg ccaggagcag gagctgaaaa 27420taaaaaacag atctctgcgc tccctcaccc gcagctgtct gtatcacaaa agcgaagatc 27480agcttcggcg cacgctggag gacgcggagg cactcttcag caaatactgc gcgctcactc 27540ttaaagacta gctccgcgcc cttctcgaat ttaggcggga gaaaactacg tcatcgccgg 27600ccgccgccca gcccgcccag ccgagatgag caaagagatt cccacgccat acatgtggag 27660ctaccagccg cagatgggac tcgcggcggg agcggcccag gactactcca cccgcatgaa 27720ctacatgagc gcgggacccc acatgatctc acaggtcaac gggatccgcg cccagcgaaa 27780ccaaatactg ctggaacagg cggccatcac cgccacgccc cgccataatc tcaacccccg 27840aaattggccc gccgccctcg tgtaccagga aaccccctcc gccaccaccg tactacttcc 27900gcgtgacgcc caggccgaag tccagatgac taactcaggg gcgcagctcg cgggcggctt 27960tcgtcacggg gcgcggccgc tccgaccagg tataagacac ctgatgatca gaggccgagg 28020
tatccagctc aacgacgagt cggtgagctc ttcgctcggt ctccgtccgg acggaacttt 28080ccagctcgcc ggatccggcc gctcttcgtt cacgccccgc caggcgtacc tgactctgca 28140gacctcgtcc tcggagcccc gctccggagg catcggaacc ctccagttcg tggaggagtt 28200cgtgccctcg gtctacttca accccttctc gggacctccc ggacgctacc ccgaccagtt 28260cattccgaac tttgacgcgg tgaaggactc ggcggacggc tacgactgaa tgtcaggtgc 28320cgaggcagag cagcttcgcc tgagacacct cgagcactgc cgccgccaca agtgcttcgc 28380ccgcggttcc ggtgagttct gctactttca gctacccgag gagcataccg aggggccggc 28440gcacggcgtc cgcctgacca cccagggcga ggttacctgt tccctcatcc gggagttcac 28500cctccgtccc ctgctagtgg agcgggagcg gggtccctgt gtcctaacta tcgcctgcaa 28560ctgccctaac cctggattac atcaagatct ttgctgtcat ctctgtgctg agtttaataa 28620acgctgagat cagaatctac tggggctcct gtcgccatcc tgtgaacgcc accgtcttca 28680cccaccccga ccaggcccag gcgaacctca cctgcggtct gcatcggagg gccaagaagt 28740acctcacctg gtacttcaac ggcaccccct ttgtggttta caacagcttc gacggggacg 28800gagtctccct gaaagaccag ctctccggtc tcagctactc catccacaag aacaccaccc 28860tccaactctt ccctccctac ctgccgggaa cctacgagtg cgtcaccggc cgctgcaccc 28920acctcacccg cctgatcgta aaccagagct ttccgggaac agataactcc ctcttcccca 28980gaacaggagg tgagctcagg aaactccccg gggaccaggg cggagacgta ccttcgaccc 29040ttgtggggtt aggatttttt attaccgggt tgctggctct tttaatcaaa gcttccttga 29100gatttgttct ttccttctac gtgtatgaac acctcagcct ccaataactc taccctttct 29160tcggaatcag gtgacttctc tgaaatcggg cttggtgtgc tgcttactct gttgattttt 29220ttccttatca tactcagcct tctgtgcctc aggctcgccg cctgctgcgc acacatctat 29280atctactgct ggttgctcaa gtgcaggggt cgccacccaa gatgaacagg tacatggtcc 29340tatcgatcct aggcctgctg gccctggcgg cctgcagcgc cgccaaaaaa gagattacct 29400ttgaggagcc cgcttgcaat gtaactttca agcccgaggg tgaccaatgc accaccctcg 29460tcaaatgcgt taccaatcat gagaggctgc gcatcgacta caaaaacaaa actggccagt 29520ttgcggtcta tagtgtgttt acgcccggag acccctctaa ctactctgtc accgtcttcc 29580agggcggaca gtctaagata ttcaattaca ctttcccttt ttatgagtta tgcgatgcgg 29640tcatgtacat gtcaaaacag tacaacctgt ggcctccctc tccccaggcg tgtgtggaaa 29700atactgggtc ttactgctgt atggctttgg caatcactac gctcgctcta atctgcacgg 29760tgctatacat aaaattcagg cagaggcgaa tctttatcga tgaaaagaaa atgccttgat 29820cgctaacacc ggctttctat ctgcagaatg aatgcaatca cctccctact aatcaccacc 29880accctccttg cgattgccca tgggttgaca cgaatcgaag tgccagtggg gtccaatgtc 29940accatggtgg gccccgccgg caattccacc ctcatgtggg aaaaatttgt ccgcaatcaa 30000tgggttcatt tctgctctaa ccgaatcagt atcaagccca gagccatctg cgatgggcaa 30060aatctaactc tgatcaatgt gcaaatgatg gatgctgggt actattacgg gcagcgggga 30120
gaaatcatta attactggcg accccacaag gactacatgc tgcatgtagt cgaggcactt 30180cccactacca cccccactac cacctctccc accaccacta ccaccactac tactactact 30240actaccacta ccgctgcccg ccatacccgc aaaagcacca tgattagcac aaagccccct 30300cgtgctcact cccacgccgg cgggcccatc ggtgcgacct cagaaaccac cgagctttgc 30360ttctgccaat gcactaacgc cagcgctcat gaactgttcg acctggagaa tgaggatgcc 30420cagcagagct ccgcttgcct gacccaggag gctgtggagc ccgttgccct gaagcagatc 30480ggtgattcaa taattgactc ttcttctttt gccactcccg aataccctcc cgattctact 30540ttccacatca cgggtaccaa agaccctaac ctctctttct acctgatgct gctgctctgt 30600atctctgtgg tctcttccgc gctgatgtta ctggggatgt tctgctgcct gatctgccgc 30660agaaagagaa aagctcgctc tcagggccaa ccactgatgc ccttccccta ccccccggat 30720tttgcagata acaagatatg agctcgctgc tgacactaac cgctttacta gcctgcgctc 30780taacccttgt cgcttgcgac tcgagattcc acaatgtcac agctgtggca ggagaaaatg 30840ttactttcaa ctccacggcc gatacccagt ggtcgtggag tggctcaggt agctacttaa 30900ctatctgcaa tagctccact tcccccagca tatccccaac caagtaccaa tgcaatgcca 30960gcctgttcac cctcatcaac gcttccaccc tggacaatgg actctatgta ggctatgtac 31020cctttggtgg gcaaggaaag acccacgctt acaacctgga agttcgccag cccagaacca 31080ctacccaagc ttctcccacc accaccacca ccaccaccac caccatcacc agcagcagca 31140gcagccacag cagcagcagc agattattga ctttggtttt ggccagctca tctgccgcta 31200cccaggccat ctacagctct gtgcccgaaa ccactcagat ccaccgccca gaaacgacca 31260ccgccaccac cctacacacc tccagcgatc agatgccgac caacatcacc cccttggctc 31320ttcaaatggg acttacaagc cccactccaa aaccagtgga tgcggccgag gtctccgccc 31380tcgtcaatga ctgggcgggg ctgggaatgt ggtggttcgc cataggcatg atggcgctct 31440gcctgcttct gctctggctc atctgctgcc tccaccgcag gcgagccaga ccccccatct 31500atagacccat cattgtcctg aaccccgata atgatgggat ccatagattg gatggcctga 31560aaaacctact tttttctttt acagtatgat aaattgagac atgcctcgca ttttcttgta 31620catgttcctt ctcccacctt ttctggggtg ttctacgctg gccgctgtgt ctcacctgga 31680ggtagactgc ctctcaccct tcactgtcta cctgctttac ggattggtca ccctcactct 31740catctgcagc ctaatcacag taatcatcgc cttcatccag tgcattgatt acatctgtgt 31800gcgcctcgca tacttcagac accacccgca gtaccgagac aggaacattg cccaacttct 31860aagactgctc taatcatgca taagactgtg atctgccttc tgatcctctg catcctgccc 31920accctcacct cctgccagta caccacaaaa tctccgcgca aaagacatgc ctcctgccgc 31980ttcacccaac tgtggaatat acccaaatgc tacaacgaaa agagcgagct ctccgaagct 32040tggctgtatg gggtcatctg tgtcttagtt ttctgcagca ctgtctttgc cctcatgatc 32100tacccctact ttgatttggg atggaacgcg atcgatgcca tgaattaccc cacctttccc 32160gcacccgaga taattccact gcgacaagtt gtacccgttg tcgttaatca acgcccccca 32220
tcccctacgc ccactgaaat cagctacttt aacctaacag gcggagatga ctgacgccct 32280agatctagaa atggacggca tcagtaccga gcagcgtctc ctagagaggc gcaggcaggc 32340ggctgagcaa gagcgcctca atcaggagct ccgagatctc gttaacctgc accagtgcaa 32400aagaggcatc ttttgtctgg taaagcaggc caaagtcacc tacgagaaga ccggcaacag 32460ccaccgcctc agttacaaat tgcccaccca gcgccagaag ctggtgctca tggtgggtga 32520gaatcccatc accgtcaccc agcactcggt agagaccgag gggtgtctgc actctccctg 32580tcggggtcca gaagacctct gcaccctggt aaagaccctg tgcggtctca gagatttagt 32640cccctttaac taatcaaaca ctggaatcaa taaaaagaat cacttactta aaatcagaca 32700gcaggtctct gtccagttta ttcagcagca cctccttccc ctcctcccaa ctctggtact 32760ccaaacgcct tctggcggca aacttcctcc acaccctgaa gggaatgtca gattcttgct 32820cctgtccctc cgcacccact atcttcatgt tgttgcagat gaagcgcacc aaaacgtctg 32880acgagagctt caaccccgtg tacccctatg acacggaaag cggccctccc tccgtccctt 32940tcctcacccc tcccttcgtg tctcccgatg gattccaaga aagccccccc ggggtcctgt 33000ctctgaacct ggccgagccc ctggtcactt cccacggcat gctcgccctg aaaatgggaa 33060gtggcctctc cctggacgac gctggcaacc tcacctctca agatatcacc accgctagcc 33120ctcccctcaa aaaaaccaag accaacctca gcctagaaac ctcatccccc ctaactgtaa 33180gcacctcagg cgccctcacc gtagcagccg ccgctcccct ggcagtggcc ggcacctccc 33240tcaccatgca atcagaggcc cccctgacag tacaggatgc aaaactcacc ctggccacca 33300aaggccccct gaccgtgtct gaaggcaaac tggccttgca aacatcggcc ccgctgacgg 33360ccgctgacag cagcaccctc accgttagcg ccacaccacc aattaatgta agcagtggaa 33420gtttaggctt agacatggaa gaccctatgt atactcacga tggaaaactg ggaataagaa 33480ttgggggtcc actaagagta gtagacagct tgcacacact cactgtagtt accggaaatg 33540gactaactgt agataacaat gccctccaaa ctagagttac gggcgcccta ggttatgaca 33600catcaggaaa tctacaattg agagctgcag gaggtatgcg aattgatgca aatggccaac 33660ttatccttaa tgtggcatac ccatttgatg ctcagaacaa tctcagcctt agacttggtc 33720agggacccct gtatataaac acagaccaca acctggattt gaattgcaac agaggtctaa 33780ccacaactac caccaacaac acaaaaaaac ttgagactaa aattagctca ggcttagact 33840atgacaccaa tggtgctgtc attattaaac ttggcactgg tctaagcttc gacaacacag 33900gcgccctaac tgtgggaaac actggtgatg ataaactgac tctgtggacg accccagacc 33960catctccaaa ttgcagaatt cactcagaca aagactgcaa gtttactcta gtcctaacta 34020agtgtggaag ccaaatcctg gcctctgtcg ccgccctagc ggtatcagga aatctggctt 34080cgataacagg caccgttgcc agcgttacca tctttctcag atttgatcag aatggagtgc 34140ttatggaaaa ctcctcgcta gacaggcagt actggaactt cagaaatggc aactcaacta 34200acgctgcccc ctacaccaat gcagttgggt tcatgccaaa cctcgcagca taccccaaaa 34260cgcaaagcca gactgctaaa aacaacattg taagtcaggt ttacttgaat ggagacaaat 34320
ccaaacccat gacccttacc atcaccctca atggaactaa tgaatccagt gaaactagcc 34380aggtgagtca ctactccatg tcatttacat gggcttggga aagtgggcaa tatgccactg 34440aaacctttgc caccaactcc ttcacctttt cttacattgc tgaacaataa aaagcatgac 34500actgatgttc atttctgatt cttattttat tattttcaaa cacaacaaaa tcattcaagt 34560cattcttcca tcttagctta atagacacag tagcttaata gacccagtag tgcaaagccc 34620cattctagct tatagatcag acagtgataa ttaaccacca ccaccaccat accttttgat 34680tcaggaaatc atgatcatca caggatccta gtcttcaggc cgccccctcc ctcccaagac 34740acagaataca cagtcctctc cccccgactg gctttaaata acaccatctg gttggtcaca 34800gacatgttct taggggttat attccacacg gtctcctgcc gcgccaggcg ctcgtcggtg 34860atgttgataa actctcccgg cagctcgctc aagttcacgt cgctgtccag cggctgaacc 34920tccggctgac gcgataactg tgcgaccggc tgctggacaa acggaggccg cgcctacaag 34980ggggtagagt cataatcctc ggtcaggata gggcggtgat gcagcagcag cgagcgaaac 35040atctgctgcc gccgccgctc cgtccggcag gaaaacaaca agccggtggt ctcctccgcg 35100ataatccgca ccgcccgcag catcagcttc ctcgttctcc gcgcgcagca cctcaccctg 35160atctcgctca agtcggcgca gtaggtacag cacagcacca cgatgttatt catgatccca 35220cagtgcaggg cgctgtatcc aaagctcatg ccgggaacca ccgcccccac gtggccatcg 35280taccacaagc gcacgtaaat taagtgtcga cccctcatga acgtgctgga cacaaacatt 35340acttccttgg gcatgttgta attcaccacc tcccggtacc agataaacct ctggttaaac 35400agggcacctt ccaccaccat cctgaaccaa gaggccagaa cctgcccacc ggctatgcac 35460tgcagggaac ccgggttgga acaatgacaa tgcagactcc aaggctcgta accgtggatc 35520atccggctgc tgaaggcatc gatgttggca caacacagac acacgtgcat gcactttctc 35580atgattagca gctcttccct cgtcaggatc atatcccaag gaataaccca ttcttgaatc 35640aacgtaaaac ccacacagca gggaaggcct cgcacataac tcacgttgtg catggtcagc 35700gtgttgcatt ctggaaacag cggatgatcc tccagtatcg aggcgcgggt ctccttctca 35760cagggaggta aagggtccct gctgtacgga ctgcgccggg acgaccgaga tcgtgttgag 35820cgtagtgtca tggaaaaggg aacgccggac gtggtcatac ttcttgaagc agaaccaggt 35880tcgcgcgtgg caggcctcct tgcgtctgcg gtctcgccgt ctagctcgct ccgtgtgata 35940gttgtagtac agccactccc gcagagcgtc gaggcgcacc ctggcttccg gatctatgta 36000gactccgtct tgcaccgcgg ccctgataat atccaccacc gtagaataag caacacccag 36060ccaagcaata cactcgctct gcgagcggca gacaggagga gcgggcagag atgggagaac 36120catgataaaa aacttttttt aaagaatatt ttccaattct tcgaaagtaa gatctatcaa 36180gtggcagcgc tcccctccac tggcgcggtc aaactctacg gccaaagcac agacaacggc 36240atttctaaga tgttccttaa tggcgtccaa aagacacacc gctctcaagt tgcagtaaac 36300tatgaatgaa aacccatccg gctgattttc caatatagac gcgccggcgg cgtccaccaa 36360acccagataa ttttcttctc tccagcggtt tagaatctgt ctaagcaaat cccttatatc 36420
aagtccggcc atgccaaaaa tctgctcaag agcgccctcc accttcatga ccaagcagcg 36480catcatgatt gcaaaaattc aggttcttca gagacctgta taagattcaa aatgggaaca 36540ttaacaaaaa ttcctctgtc gcgcagatcc cttcgcaggg caagctgaac ataatcagac 36600aggtctgaac ggaccagtga ggccaaatcc ccaccaggaa ccagatccag agaccctata 36660ctgattatga cgcgcatact cggggctatg ctgaccagcg tagcgccgat gtaggcgtgc 36720tgcatgggcg gcgagataaa atgcaaagtg ctggttaaaa aatcaggcaa agcctcgcgc 36780aaaaaagcta acacatcata atcatgctca tgcaggtagt tgcaggtaag ctcaggaacc 36840aaaacggaat aacacacgat tttcctctca aacatgactt cgcggatact gcgtaaaaca 36900aaaattataa ataaaaaatt aattaactta aacattggaa gcctgtctca caacaggaaa 36960aaccacttta atcaacataa gacgggccac gggcatgccg gcatagccgt aaaaaaattg 37020gtccccgtga ttaacaagta ccacagacag ctccccggtc atgtcggggg tcatcatgtg 37080agactctgta tacacgtctg gattgtgaac atcagacaaa caaagaaatc gagccacgta 37140gcccggaggt ataatcaccc gcaggcggag gtacagcaaa acgaccccca taggaggaat 37200cacaaaatta gtaggagaaa aaaatacata aacaccagaa aaaccctgtt gctgaggcaa 37260aatagcgccc tcccgatcca aaacaacata aagcgcttcc acaggagcag ccataacaaa 37320gacccgagtc ttaccagtaa aagaaaaaag atctctcaac gcagcaccag caccaacact 37380tcgcagtgta aaaggccaag tgccgagaga gtatatatag gaataaaaag tgacgtaaac 37440gggcaaagtc caaaaaacgc ccagaaaaac cgcacgcgaa cctacgcccc gaaacgaaag 37500ccaaaaaaca ctagacactc ccttccggcg tcaacttccg ctttcccacg ctacgtcact 37560tgccccagtc aaacaaacta catatcccga acttccaagt cgccacgccc aaaacaccgc 37620ctacacctcc ccgcccgccg gcccgccccc aaacccgcct cccgccccgc gccccgcctc 37680gcgccgccca tctcattatc atattggctt caatccaaaa taaggtatat tattgatgat 37740g 37741210221136648212DNA213黑猩猩腺病毒-ChAd6基因組4002catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agccgtttga 60atttggggat gcggggcgct gattggctgc gggagcggcg accgttaggg gcggggcggg 120tgacgttttg atgacgtgtt tgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300
aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600gtaatgtttt cctggctact gggaacgaga ttctggaact ggtggtggac gccatgatgg 660gtgacgaccc tcctgagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780gcgatgccgc gctgctggcc gccgagcagg ctaatacgga ctctggctca gacagcgatt 840cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960aggaggcgat tcgagctgca gcgagcgagg gagtgaaagc tgcgggcgag agctttagcc 1020tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140acagtaagtg tgattaactt tagctgggaa ggcagagggt gactgggtgc tgactggttt 1200atttatgtat atgtttttta tgtgtaggtc ccgtctctga cgtagatgag acccccactt 1260cagagtgcat ttcatcaccc ccagaaattg gcgaggaacc gcccgaagat attattcata 1320gaccagttgc agtgagagtc accgggcgga gagcagctgt ggagagtttg gatgacttgc 1380tacagggtgg ggatgaacct ttggacttgt gtacccggaa acgccccagg cactaagtgc 1440cacacatgtg tgtttactta aggtgatgtc agtatttata gggtgtggag tgcaataaaa 1500tccgtgttga ctttaagtgt gtggtttatg actcaggggt ggggactgtg ggtatataag 1560caggtgcaga cctgtgtggt cagttcagag caggactcat ggagatctgg acggtcttgg 1620aagactttca ccagactaga cagctgctag agaactcatc ggaggaagtc tcttacctgt 1680ggagattttg cttcggtggg gctctagcta agctagtcta tagggccaaa caggattata 1740aggatcaatt tgaggatatt ttgagagagt gtcctagtat ttttgactct ctcaacttgg 1800gccatcagtc tcactttaac cagagtattc tgagagccct tgacttttct actcctggca 1860gaactaccgc cgcggtagcc ttttttgcct ttattcttga caaatggagt caagaaaccc 1920atttcagcag ggattaccgt ctggactgct tagcagtagc tttgtggaga acatggaggt 1980gccagcgcct gaatgcaatc tccggctact tgccagtaca gccggtagac acgctgagga 2040tcctgagtct ccagtcaccc caggaacacc aacgccgcca gcagccgcag caggagcagc 2100agcaagagga ggaggaggag gaggaccgag aagagaaccc gagagccggt ctggaccctc 2160cggtggcgga ggaggaggag tagctgactt gtttcccgag ctgcgccggg tgctgactag 2220gtcttccagt ggacgggaga gggggattaa gcgggagagg catgaggaga ctagtcacag 2280aactgaactg actgtcagtc tgatgagccg caggcgccca gaatcggtgt ggtggcatga 2340ggttcagtcg caggggatag atgaggtctc ggtaatgcat gagaaatatt ccctagaaca 2400
agtcaagact tgttggttgg agcccgagga tgattgggag gtagccatca ggaattatgc 2460caagctggct ctgaggccag acaagaagta caagattacc aaactgatta atatcagaaa 2520ttcctgctac atttcgggga atggggccga ggtggagatc agtacccagg agagggtggc 2580cttcagatgt tgtatgatga atatgtaccc gggggtggtg ggcatggagg gagtcacctt 2640tatgaacgcg aggtttaggg gtgatgggta taatggggtg gtctttatgg ccaacaccaa 2700gctgacagtg cacggatgct ccttctttgg cttcaataac atgtgcatcg aggcctgggg 2760cagtgtttca gtgaggggat gcagcttttc agccaactgg atgggggtcg tgggcagaac 2820caagagcgtg gtgtcagtga agaaatgcct gttcgagagg tgccacctgg gggtgatgag 2880cgagggcgaa gccaaagtca aacactgcgc ctctaccgag acgggctgct ttgtgatgat 2940caagggcaat gccaaagtca agcataacat gatttgtggg gcctcggatg agcgcggcta 3000ccagatgctg acctgtgccg gtgggaacag ccatatgctg gccaccgtgc atgtggcctc 3060gcacccccgc aagacatggc ccgagttcga gcacaacgtc atgacccgct gcaatgtgca 3120cctggggtcc cgccgaggca tgttcatgcc ctaccagtgc aacatgcaat ttgtgaaggt 3180gctgctggag cccgatgcca tgtccagagt gagcctggtg ggggtgtttg acatgaatgt 3240ggaggtgtgg aaaattctga gatatgatga atccaagacc aggtgccggg cctgcgaatg 3300cggaggcaag cacgccaggc ttcagcccgt gtgtgtggag gtgacggagg acctgcgacc 3360cgatcatttg gtgttgtcct gcaacgggac ggagttcggc tccagcgggg aagaatctga 3420ctagagtgag tagtgtttgg gggtgggtgg gagtctgcat gatgggcaga atgactaaaa 3480tctgtgtttt tctgcgcagc agcatgagcg gaagcgcctc ctttgaggga ggggtattca 3540gcccttatct gacggggcgt ctcccctcct gggcgggagt gcgtcagaat gtgatgggat 3600ccacggtgga cggccggccc gtgcagcccg cgaactcttc aaccctgacc tacgcgaccc 3660tgagctcctc gtccgtggac gcagctgccg ccgcagctgc tgcttccgcc gccagcgccg 3720tgcgcggaat ggccttgggc gccggctact acagctctct ggtggccaac tcgagttcca 3780ccaataatcc cgccagcctg aacgaggaga agctgctgct gctgatggcc cagctcgagg 3840ccctgaccca gcgcctgggc gagctgaccc agcaggtggc tcagctgcag gcggagacgc 3900gggccgcggt tgccacggtg aaaaccaaat aaaaaatgaa tcaataaata aacggagacg 3960gttgttgatt ttaacacaga gtcttgatct ttatttgatt tttcgcgcgc ggtaggccct 4020ggaccaccgg tctcgatcat tgagcacccg gtggattttt tccaggaccc ggtagaggtg 4080ggcttggatg ttgaggtaca tgggcatgag cccgtcccgg gggtggaggt agctccattg 4140cagggcctcg tgctcggggg tggtgttgta aatcacccag tcatagcagg ggcgcagggc 4200gtggtgctgc acgatgtcct tgaggaggag actgatggcc acgggcagcc ccttggtgta 4260ggtgttgacg aacctgttga gctgggaggg atgcatgcgg ggggagatga gatgcatctt 4320ggcctggatc ttgagattgg cgatgttccc gcccagatcc cgccgggggt tcatgttgtg 4380caggaccacc agcacggtgt atccggtgca cttggggaat ttgtcatgca acttggaagg 4440gaaggcgtga aagaatttgg agacgccctt gtgaccgccc aggttttcca tgcactcatc 4500
catgatgatg gcgatgggcc cgtgggcggc ggcctgggca aagacgtttc gggggtcgga 4560cacatcgtag ttgtggtcct gggtgagctc gtcataggcc attttaatga atttggggcg 4620gagagtgccc gactggggga cgaaggtgcc ctcgatcccg ggggcgtagt tcccctcgca 4680gatctgcatc tcccaggcct tgagctcgga gggggggatc atgtccacct gcggggcgat 4740gaaaaaaacg gtttccgggg cgggggagat gagctgggcc gaaagcaggt tccggagcag 4800ctgggacttg ccgcagccgg tgggaccgta gatgaccccg atgaccggct gcaggtggta 4860gttgagggag agacagctgc catcctcgcg gaggaggggg gccacctcgt tcatcatctc 4920gcgcacatgc atgttctcgc gcacgagttc cgccaggagg cgctcgcccc ccagcgagag 4980gagctcttgc agcgaggcga agtttttcag cggcttgagc ccgtcggcca tgggcatttt 5040ggagagggtc tgttgcaaga gttccagacg gtcccagagc tcggtgatgt gctctagggc 5100atctcgatcc agcagacctc ctcgtttcgc gggttggggc gactgcggga gtagggcacc 5160aggcgatggg cgtccagcga ggccagggtc cggtccttcc agggtcgcag ggtccgcgtc 5220agcgtggtct ccgtcacggt gaaggggtgc gcgccgggct gggcgcttgc gagggtgcgc 5280ttcaggctca tccggctggt cgagaaccgc tcccggtcgg cgccctgcgc gtcggccagg 5340tagcaattga gcatgagttc gtagttgagc gcctcggccg cgtggccctt ggcgcggagc 5400ttacctttgg aagtgtgtcc gcagacggga cagaggaggg acttgagggc gtagagcttg 5460ggggcgagga agacggactc gggggcgtag gcgtccgcgc cgcagctggc gcagacggtc 5520tcgcactcca cgagccaggt gaggtcgggg cggtcggggt caaaaacgag gtttcctccg 5580tgctttttga tgcgtttctt acctctggtc tccatgagct cgtgtccccg ctgggtgaca 5640aagaggctgt ccgtgtcccc gtagaccgac tttatgggcc ggtcctcgag cggggtgccg 5700cggtcctcgt cgtagaggaa ccccgcccac tccgagacga aggcccgggt ccaggccagc 5760acgaaggagg ccacgtggga ggggtagcgg tcgttgtcca ccagcgggtc caccttctcc 5820agggtatgca agcacatgtc cccctcgtcc acatccagga aggtgattgg cttgtaagtg 5880taggccacgt gaccgggggt cccggccggg ggggtataaa agggggcggg cccctgctcg 5940tcctcactgt cttccggatc gctgtccagg agcgccagct gttggggtag gtattccctc 6000tcgaaggcgg gcatgacctc ggcactcagg ttgtcagttt ctagaaacga ggaggatttg 6060atattgacgg tgccgttgga gacgcctttc atgagcccct cgtccatctg gtcagaaaag 6120acgatctttt tgttgtcgag cttggtggcg aaggagccgt agagggcgtt ggagaggagc 6180ttggcgatgg agcgcatggt ctggttcttt tccttgtcgg cgcgctcctt ggcggcgatg 6240ttgagctgca cgtactcgcg cgccacgcac ttccattcgg ggaagacggt ggtgagctcg 6300tcgggcacga ttctgacccg ccagccgcgg ttgtgcaggg tgatgaggtc cacgctggtg 6360gccacctcgc cgcgcagggg ctcgttggtc cagcagaggc gcccgccctt gcgcgagcag 6420aaggggggca gcgggtccag catgagctcg tctggggggt cggcgtccac ggtgaagatg 6480ccgggcagga gctcggggtc gaagtagctg atggaagtgg ccagatcgtc cagggaagct 6540tgccagtcgc gcacggccag cgcgcgctcg taggggctga ggggcgtgcc ccagggcatg 6600
gggtgcgtga gcgcggaggc gtacatgccg cagatgtcgt agacgtagag gggctcctcg 6660aggatgccga tgtaggtggg gtagcagcgc cccccgcgga tgctggcgcg cacgtagtcg 6720tacagctcgt gcgagggcgc gaggagcccc gtgccgagat tggagcgctg cggcttttcg 6780gcgcggtaga cgatctggcg gaagatggcg tgggagttgg aggagatggt gggcctctgg 6840aagatgttga agtgggcgtg gggcaggccg accgagtccc tgatgaagtg ggcgtaggag 6900tcctgcagct tggcgacgag ctcggcggtg acgaggacgt ccagggcgca gtagtcgagg 6960gtctcttgga tgatgtcata cttgagctgg cccttctgct tccacagctc gcggttgaga 7020aggaactctt cgcggtcctt ccagtactct tcgaggggga acccgtcctg atcggcacgg 7080taagagccca ccatgtagaa ctggttgacg gccttgtagg cgcagcagcc cttctccacg 7140gggagggcgt aagcttgcgc ggccttgcgc agggaggtgt gggtgagggc gaaggtgtcg 7200cgcaccatga ccttgaggaa ctggtgcttg aagtcgaggt cgtcgcagcc gccctgctcc 7260cagagttgga agtccgtgcg cttcttgtag gcggggttgg gcaaagcgaa agtaacatcg 7320ttgaagagga tcttgcccgc gcggggcatg aagttgcgag tgatgcggaa aggctggggc 7380acctcggccc ggttgttgat gacctgggcg gcgaggacga tctcgtcgaa gccgttgatg 7440ttgtgcccga cgatgtagag ttccacgaat cgcgggcggc ccttgacgtg gggcagcttc 7500ttgagctcgt cgtaggtgag ctcggcgggg tcgctgagcc cgtgctgttc gagggcccag 7560tcggcgacgt gggggttggc gctgaggaag gaagtccaga gatccacggc cagggcggtc 7620tgcaagcggt cccggtactg acggaactgc tggcccacgg ccattttttc gggggtgacg 7680cagtagaagg tgcgggggtc gccgtgccag cggtcccact tgagctggag ggcgaggtcg 7740tgggcgagct cgacgagcgg tgggtccccg gagagtttca tgaccagcat gaaggggacg 7800agctgcttgc cgaaggaccc catccaggtg taggtttcca catcgtaggt gaggaagagc 7860ctttcggtgc gaggatgcga gccgatgggg aagaactgga tctcctgcca ccagttggag 7920gaatggctgt tgatgtgatg gaagtagaaa tgccgacggc gcgccgagca ctcgtgcttg 7980tgtttataca agcgtccgca gtgctcgcaa cgctgcacgg gatgcacgtg ctgcacgagc 8040tgtacctgag ttcctttgac gaggaatttc agtgggcagt ggagcgctgg cggctgcatc 8100tggtgctgta ctacgtcctg gccatcggcg tggccatcgt ctgcctcgat ggtggtcatg 8160ctgacgaggc cgcgcgggag gcaggtccag acctcggctc ggacgggtcg gagagcgagg 8220acgagggcgc gcaggccgga gctgtccagg gtcctgagac gctgcggagt caggtcagtg 8280ggcagcggcg gcgcgcggtt gacttgcagg agcttttcca gggcgcgcgg gaggtccaga 8340tggtacttga tctccacggc gccgttggtg gcgacgtcca cggcttgcag ggtcccgtgc 8400ccctggggcg ccaccaccgt gccccgtttc ttcttgggcg ctggttccat gccggtcaga 8460agcggcggcg aggacgcgcg ccgggcggca ggggcggctc ggggcccgga ggcaggggcg 8520gcaggggcac gtcggcgccg cgcgcgggca ggttctggta ctgcgcccgg agaagactgg 8580cgtgagcgac gacgcgacgg ttgacgtcct ggatctgacg cctctgggtg aaggccacgg 8640gacccgtgag tttgaacctg aaagagagtt cgacagaatc aatctcggta tcgttgacgg 8700
cggcctgccg caggatctct tgcacgtcgc ccgagttgtc ctggtaggcg atctcggtca 8760tgaactgctc gatctcctcc tcctgaaggt ctccgcggcc ggcgcgctcg acggtggccg 8820cgaggtcgtt ggagatgcgg cccatgagct gcgagaaggc gttcatgccg gcctcgttcc 8880agacgcggct gtagaccacg gctccgtcgg ggtcgcgcgc gcgcatgacc acctgggcga 8940ggttgagctc gacgtggcgc gtgaagaccg cgtagttgca gaggcgctgg tagaggtagt 9000tgagcgtggt ggcgatgtgc tcggtgacga agaagtacat gatccagcgg cggagcggca 9060tctcgctgac gtcgcccagg gcttccaagc gctccatggc ctcgtagaag tccacggcga 9120agttgaaaaa ctgggagttg cgcgccgaga cggtcaactc ctcctccaga agacggatga 9180gctcggcgat ggtggcgcgc acctcgcgct cgaaggcccc ggggggctcc tcttcttcca 9240tctcctcctc ctcttcctcc tccactaaca tctcttctac ttcctcctca ggaggcggtg 9300gcgggggagg ggccctgcgt cgccggcggc gcacgggcag acggtcgatg aagcgctcga 9360tggtctcccc gcgccggcga cgcatggtct cggtgacggc gcgcccgtcc tcgcggggcc 9420gcagcgtgaa gacgccgccg cgcatctcca ggtggccgcc gggggggtct ccgttgggca 9480gggagagggc gctgacgatg catcttatca attggcccgt agggactccg cgcaaggacc 9540tgagcgtctc gagatccacg ggatccgaaa accgctgaac gaaggcttcg agccagtcgc 9600agtcgcaagg taggctgagc ccggtttctt cgggtatttg gtcgggaggc gggcgggcga 9660tgctgctggt gatgaagttg aagtaggcgg tcctgagacg gcggatggtg gcgaggagca 9720ccaggtcctt gggcccggct tgctggatgc gcagacggtc ggccatgccc caggcgtggt 9780cctgacacct ggcgaggtcc ttgtagtagt cctgcatgag ccgctccacg ggcacctcct 9840cctcgcccgc gcggccgtgc atgcgcgtga gcccgaaccc gcgctgcggc tggacgagcg 9900ccaggtcggc gacgacgcgc tcggcgagga tggcctgctg gatctgggtg agggtggtct 9960ggaagtcgtc gaagtcgacg aagcggtggt aggctccggt gttgatggtg tatgagcagt 10020tggccatgac ggaccagttg acggtctggt ggccggggcg cacgagctcg tggtacttga 10080ggcgcgagta ggcgcgcgtg tcgaagatgt agtcgttgca ggtgcgcacg aggtactggt 10140atccgacgag gaagtgcggc ggcggctggc ggtagagcgg ccatcgctcg gtggcggggg 10200cgccgggcgc gaggtcctcg agcatgaggc ggtggtagcc gtagatgtac ctggacatcc 10260aggtgatgcc ggcggcggtg gtggaggcgc gcgggaactc gcggacgcgg ttccagatgt 10320tgcgcagcgg caggaagtag ttcatggtgg ccgcggtctg gcccgtgagg cgcgcgcagt 10380cgtggatgct ctatacgggc aaaaacgaaa gcggtcagcg gctcgactcc gtggcctgga 10440ggctaagcga acgggttggg ctgcgcgtgt accccggttc gaatctcgaa tcaggctgga 10500gccgcagcta acgtggtact ggcactcccg tctcgaccca agcctgcaca aaacctccag 10560gatacggagg cgggtcgttt tgcaactttt tgaggccgga aatgaaacta gtaagcgcga 10620aaagcggccg accgcgatgg ctcgctgccg tagtctggag aagaatcgcc agggttgcgt 10680tgcggtgtgc cccggttcga ggccggccgg attccgcggc taacgagggc gtggctgccc 10740cgtcgtttcc aagaccccta gccagccgac ttctccagtt acggagcgag cccctctttt 10800
gttttgtttg tttttgccag atgcatcccg tactgcggca gatgcgcccc caccaccctc 10860caccgcaaca acagcccact ccacagccgg cgcttctgcc cccgccccag cagcagcaac 10920ttccagccac gaccgccgcg gccgccgtga gcggggctgg acagacttct cagtatgacc 10980acctggcctt ggaagagggc gaggggctgg cgcgcctggg ggcgtcgtcg ccggagcggc 11040acccgcgcgt gcagatgaaa cgggacgctc gcgaggccta cgtgcccaag cagaacctgt 11100tcagagacag gagcggcgag gagcccgagg agatgcgcgc ggcccggttc cacgcggggc 11160gggagctgcg gcgcggcctg gaccgaaaga gggtgctgag ggacgaggat ttcgaggcgg 11220acgagctgac ggggatcagc cccgcgcgcg cgcacgtggc cgcggccaac ctggtcacgg 11280cgtacgagca gaccgtgaag gaggagagca acttccaaaa atccttcaac aaccacgtgc 11340gcaccctgat cgcgcgcgag gaggtgaccc tgggcctgat gcacctgtgg gacctgctgg 11400aggccatcgt gcagaacccc accagcaagc cgctgacggc gcagctgttc ctggtggtgc 11460agcacagtcg ggacaacgag gcgttcaggg aggcgctgct gaatatcacc gagcccgagg 11520gccgctggct cctggacctg gtgaacattc tgcagagcat cgtggtgcag gagcgcgggc 11580tgccgctgtc cgagaagctg gcggccatca acttctcggt gctgagtctg ggcaagtact 11640acgctaggaa gatctacaag accccgtacg tgcccataga caaggaggtg aagatcgacg 11700ggttttacat gcgcatgacc ctgaaagtgc tgaccctgag cgacgatctg ggggtgtacc 11760gcaacgacag gatgcaccgc gcggtgagcg ccagccgccg gcgcgagctg agcgaccagg 11820agctgatgca cagcctgcag cgggccctga ccggggccgg gaccgagggg gagagctact 11880ttgacatggg cgcggacctg cgctggcagc ccagccgccg ggccttggaa gctgccggcg 11940gttcccccta cgtggaggag gtggacgatg aggaggagga gggcgagtac ctggaagact 12000gatggcgcga ccgtattttt gctagatgca gcaacagcca ccgccgcctc ctgatcccgc 12060gatgcgggcg gcgctgcaga gccagccgtc cggcattaac tcctcggacg attggaccca 12120ggccatgcaa cgcatcatgg cgctgacgac ccgcaatccc gaagccttta gacagcagcc 12180tcaggccaac cggctctcgg ccatcctgga ggccgtggtg ccctcgcgct cgaaccccac 12240gcacgagaag gtgctggcca tcgtgaacgc gctggtggag aacaaggcca tccgcggcga 12300cgaggccggg ctggtgtaca acgcgctgct ggagcgcgtg gcccgctaca acagcaccaa 12360cgtgcagacg aacctggacc gcatggtgac cgacgtgcgc gaggcggtgt cgcagcgcga 12420gcggttccac cgcgagtcga acctgggctc catggtggcg ctgaacgcct tcctgagcac 12480gcagcccgcc aacgtgcccc ggggccagga ggactacacc aacttcatca gcgcgctgcg 12540gctgatggtg gccgaggtgc cccagagcga ggtgtaccag tcggggccgg actacttctt 12600ccagaccagt cgccagggct tgcagaccgt gaacctgagc caggctttca agaacttgca 12660gggactgtgg ggcgtgcagg ccccggtcgg ggaccgcgcg acggtgtcga gcctgctgac 12720gccgaactcg cgcctgctgc tgctgctggt ggcgcccttc acggacagcg gcagcgtgag 12780ccgcgactcg tacctgggct acctgcttaa cctgtaccgc gaggccatcg ggcaggcgca 12840cgtggacgag cagacctacc aggagatcac ccacgtgagc cgcgcgctgg gccaggagga 12900
cccgggcaac ctggaggcca ccctgaactt cctgctgacc aaccggtcgc agaagatccc 12960gccccagtac gcgctgagca ccgaggagga gcgcatcctg cgctacgtgc agcagagcgt 13020ggggctgttc ctgatgcagg agggggccac gcccagcgcc gcgctcgaca tgaccgcgcg 13080caacatggag cccagcatgt acgcccgcaa ccgcccgttc atcaataagc tgatggacta 13140cttgcatcgg gcggccgcca tgaactcgga ctactttacc aacgccatct tgaacccgca 13200ctggctcccg ccgcccgggt tctacacggg cgagtatgac atgcccgacc ccaacgacgg 13260gttcctgtgg gatgacgtgg acagcagcgt gttctcgccg cgccccgcca ccaccgtgtg 13320gaagaaagag ggcggggacc ggcggccgtc ctcggcgctg tccggtcgcg cgggtgctgc 13380cgcggcggtg cccgaggccg ccagcccctt cccgagcctg cccttttcgc tgaacagcgt 13440gcgcagcagc gagctgggac ggctgacgcg gccgcgcctg ctgggcgagg aggagtacct 13500gaacgactcc ttgttgaggc ccgagcgcga gaagaacttc cccaataacg ggatagagag 13560cctggtggac aagatgagcc gctggaagac gtacgcgcac gagcacaggg acgagccgcg 13620agctagcagc agcaccggcg cccgtagacg ccagcggcac gacaggcagc ggggactggt 13680gtgggacgat gaggattccg ccgacgacag cagcgtgttg gacttgggtg ggagtggtgg 13740tggtaacccg ttcgctcacc tgcgcccccg tatcgggcgc ctgatgtaag aatctgaaaa 13800aataaaaaac ggtactcacc aaggccatgg cgaccagcgt gcgttcttct ctgttgtttg 13860tagtagtatg atgaggcgcg tgtacccgga gggtcctcct ccctcgtacg agagcgtgat 13920gcagcaggcg gtggcggcgg cgatgcagcc cccgctggag gcgccttacg tgcccccgcg 13980gtacctggcg cctacggagg ggcggaacag cattcgttac tcggagctgg cacccttgta 14040cgataccacc cggttgtacc tggtggacaa caagtcggcg gacatcgcct cgctgaacta 14100ccagaacgac cacagcaact tcctgaccac cgtggtgcag aacaacgatt tcacccccac 14160ggaggccagc acccagacca tcaactttga cgagcgctcg cggtggggcg gccagctgaa 14220aaccatcatg cacaccaaca tgcccaacgt gaacgagttc atgtacagca acaagttcaa 14280ggcgcgggtc atggtctcgc gcaagacccc caacggggtc gcggtagggg atgattatga 14340tggtagtcag gacgagctga cctacgagtg ggtggagttt gagctgcccg agggcaactt 14400ctcggtgacc atgaccatcg atctgatgaa caacgccatc atcgacaatt acttggcggt 14460gggacggcag aacggggtgc tggagagcga catcggcgtg aagttcgaca cgcgcaactt 14520ccggctgggc tgggaccccg tgaccgagct ggtgatgccg ggcgtgtaca ccaacgaggc 14580cttccacccc gacatcgtcc tgctgcccgg ctgcggcgtg gacttcaccg agagccgcct 14640cagcaacctg ctgggcatcc gcaagcggca gcccttccag gagggcttcc agatcctgta 14700cgaggacctg gaggggggca acatccccgc gctcttggat gtcgaagcct atgaagaaag 14760taaggaaaaa gcagaggctg aggcaactgc agccgtggct actgccgctg tcaccgatgc 14820agatgcagct actaccaggg gcgatacatt cgccactgtg gctgaagaag cagccgccgt 14880agcggcgacc gatgatagtg aaagtaagat agtcatcaag ccggtggaga aggacagcaa 14940gaacaggagc tacaacgttc tatcggatgg aaagaacacc gcctaccgca gctggtacct 15000
ggcctacaac tacggcgacc ccgagaaggg cgtgcgctcc tggacgctgc tcaccacctc 15060ggacgtcacc tgcggcgtgg agcaagtcta ctggtcgctg cccgacatga tgcaagaccc 15120ggtcaccttc cgctccacgc gtcaagttag caactacccg gtggtgggcg ccgagctcct 15180gcccgtctac tccaagagct tcttcaacga gcaggccgtc tactcgcagc agctgcgcgc 15240cttcacctcg ctcacgcacg tcttcaaccg cttccccgag aaccagatcc tcgtccgccc 15300gcccgcgccc accattacca ccgtcagtga aaacgttcct gctctcacag atcacgggac 15360cctgccgctg cgcagcagta tccggggagt ccagcgcgtg accgtcactg acgccagacg 15420ccgcacctgc ccctacgtct acaaggccct gggcgtagtc gcgccgcgcg tcctctcgag 15480ccgcaccttc taaaaaatgt ccattctcat ctcgcccagt aataacaccg gttggggcct 15540gcgcgcgccc agcaagatgt acggaggcgc tcgccaacgc tccacgcaac accccgtgcg 15600cgtgcgcggg cacttccgcg ctccctgggg cgccctcaag ggccgcgtgc gctcgcgcac 15660caccgtcgac gacgtgatcg accaggtggt ggccgacgcg cgcaactaca cgcccgccgc 15720cgcgcccgtc tccaccgtgg acgccgtcat cgacagcgtg gtggccgacg cgcgccggta 15780cgcccgcgcc aagagccggc ggcggcgcat cgcccggcgg caccggagca cccccgccat 15840gcgcgcggcg cgagccttgc tgcgcagggc caggcgcacg ggacgcaggg ccatgctcag 15900ggcggccaga cgcgcggcct ctggcagcag cagcgccggc aggacccgca gacgcgcggc 15960cacggcggcg gcggcggcca tcgccagcat gtcccgcccg cggcgcggca acgtgtactg 16020ggtgcgcgac gccgccaccg gtgtgcgcgt gcccgtgcgc acccgccccc ctcgcacttg 16080aagatgctga cttcgcgatg ttgatgtgtc ccagcggcga ggaggatgtc caagcgcaaa 16140ttcaaggaag agatgctcca ggtcatcgcg cctgagatct acggccccgc ggcggcggtg 16200aaggaggaaa gaaagccccg caaactgaag cgggtcaaaa aggacaaaaa ggaggaggaa 16260gatgtggacg gactggtgga gtttgtgcgc gagttcgccc cccggcggcg cgtgcagtgg 16320cgcgggcgga aagtgaaacc ggtgctgcga cccggcacca ccgtggtctt cacgcccggc 16380gagcgttccg gctccgcctc caagcgctcc tacgacgagg tgtacgggga cgaggacatc 16440ctcgagcagg cggccgagcg tctgggcgag tttgcttacg gcaagcgcag ccgccccgcg 16500cccttgaaag aggaggcggt gtccatcccg ctggaccacg gcaaccccac gccgagtctg 16560aagccggtga ccctgcagca ggtgctgccg agcgcggcgc cgcgccgggg cttcaagcgc 16620gagggcggcg aggatctgta cccgaccatg cagctgatgg tgcccaagcg ccagaagctg 16680gaggacgtgc tggagcacat gaaggtggac cccgaggtgc agcccgaggt caaggtgcgg 16740cccatcaagc aggtggcccc gggcctgggc gtgcagaccg tggacatcaa gatccccacg 16800gagcccatgg aaacgcagac cgagcccgtg aagcccagca ccagcaccat ggaggtgcag 16860acggatccct ggatgccggc gccggcttcc accaccacca ctcgccgaag acgcaagtac 16920ggcgcggcca gcctgctgat gcccaactac gcgctgcatc cttccatcat ccccacgccg 16980ggctaccgcg gcacgcgctt ctaccgcggc tacagcagcc gccgcaagac caccacccgc 17040cgccgccgtc gtcgcacccg ccgcagcagc accgcgactt ccgccgcctt ggtgcggaga 17100
gtgtaccgca gcgggcgcga gcctctgacc ctgccgcgcg cgcgctacca cccgagcatc 17160gccatttaac tctgccgtcg cctcctactt gcagatatgg ccctcacatg ccgcctccgc 17220gtccccatta cgggctaccg aggaagaaag ccgcgccgta gaaggctgac ggggaacggg 17280ctgcgtcgcc atcaccaccg gcggcggcgc gccatcagca agcggttggg gggaggcttc 17340ctgcccgcgc tgatccccat catcgccgcg gcgatcgggg cgatccccgg catagcttcc 17400gtggcggtgc aggcctctca gcgccactga gacacagctt ggaaaatttg taataaaaaa 17460tggactgacg ctcctggtcc tgtgatgtgt gtttttagat ggaagacatc aatttttcgt 17520ccctggcacc gcgacacggc acgcggccgt ttatgggcac ctggagcgac atcggcaaca 17580gccaactgaa cgggggcgcc ttcaattgga gcagtctctg gagcgggctt aagaatttcg 17640ggtccacgct caaaacctat ggcaacaagg cgtggaacag cagcacaggg caggcgctga 17700gggaaaagct gaaagagcag aacttccagc agaaggtggt cgatggcctg gcctcgggca 17760tcaacggggt ggtggacctg gccaaccagg ccgtgcagaa acagatcaac agccgcctgg 17820acgcggtccc gcccgcgggg tccgtggaga tgccccaggt ggaggaggag ctgcctcccc 17880tggacaagcg cggcgacaag cgaccgcgtc ccgatgcaga ggagacgctg ctgacgcaca 17940cggacgagcc gcccccgtac gaggaggcgg tgaaactggg tctgcccacc acgcggcccg 18000tggcgcctct ggccaccggg gtgctgaaac ccagcagcag cagccagccc gcgaccctgg 18060acttgcctcc gcctgcttcc cgcccctcca cagtggctaa gcccctgccg ccggtggccg 18120tcgcgtcgcg cgccccccga ggccgccccc aggcgaactg gcagagcact ctgaacagca 18180tcgtgggtct gggagtgcag agtgtgaagc gccgccgctg ctattaaaag acactgtagc 18240gcttaacttg cttgtctgtg tgtatatgta tgtccgccga ccagaaggaa gaggcgcgtc 18300gccgagttgc aagatggcca ccccatcgat gctgccccag tgggcgtaca tgcacatcgc 18360cggacaggac gcttcggagt acctgagtcc gggtctggtg cagttcgccc gcgccacaga 18420cacctacttc agtctgggga acaagtttag gaaccccacg gtggcgccca cgcacgatgt 18480gaccaccgac cgcagccagc ggctgacgct gcgcttcgtg cccgtggacc gcgaggacaa 18540cacctactcg tacaaagtgc gctacacgct ggccgtgggc gacaaccgcg tgctggacat 18600ggccagcacc tactttgaca tccgcggcgt gctggatcgg ggccccagct tcaaacccta 18660ctccggcacc gcctacaaca gcctggctcc caagggagcg cccaacacct cacagtggat 18720aaccaaagac aatggaactg ataagacata cagttttgga aatgctccag tcagaggatt 18780ggacattaca gaagagggtc tccaaatagg acccgatgag tcagggggtg aaagcaagaa 18840aatttttgca gacaaaacct atcagcctga acctcagctt ggagatgagg aatggcatga 18900tactattgga gctgaagaca agtatggagg cagagcgctt aaacctgcca ccaacatgaa 18960accctgctat gggtctttcg ccaagccaac taatgctaag ggaggtcagg ctaaaagcag 19020aaccaaggac gatggcacta ctgagcctga tattgacatg gccttctttg acgatcgcag 19080tcagcaagct agtttcagtc cagaacttgt tttgtatact gagaatgtcg atctggacac 19140cccggatacc cacattattt acaaacctgg cactgatgaa acaagttctt ctttcaactt 19200
gggtcagcag tccatgccca acagacccaa ctacatcggc ttcagagaca actttatcgg 19260tctcatgtac tacaacagta ctggcaatat gggtgtacta gctggacagg cctcccagct 19320gaatgctgtg gtggacttgc aggacagaaa cactgaactg tcctaccagc tcttgcttga 19380ctctctgggt gacagaacca ggtatttcag tatgtggaac caggcggtgg acagctacga 19440ccccgatgtg cgcattattg aaaatcacgg tgtggaggat gaactaccca actattgctt 19500ccctttgaat ggtgtgggct ttacagatac attccaggga attaaggtta aaactaccaa 19560taacggaaca gcaaatgcta cagagtggga atctgatacc tctgtcaata atgctaatga 19620gattgccaag ggcaatcctt tcgccatgga gatcaacatc caggccaacc tgtggcggaa 19680cttcctctac gcgaacgtgg cgctgtacct gcccgactcc tacaagtaca cgccggccaa 19740catcacgctg cccgccaaca ccaacaccta cgattacatg aacggccgcg tggtagcgcc 19800ctcgctggtg gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggacaa 19860cgtcaacccc ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg 19920caacgggcgc tacgtgccct tccacatcca ggtgccccaa aagtttttcg ccatcaagag 19980cctcctgctc ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat 20040gatcctgcag agctccctcg gcaacgacct gcgcacggac ggggcctcca tcgccttcac 20100cagcatcaac ctctacgcca ccttcttccc catggcgcac aacaccgcct ccacgctcga 20160ggccatgctg cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa 20220catgctctac cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa 20280ctgggccgcc ttccgcggct ggtccttcac gcgcctcaag acccgcgaga cgccctcgct 20340cggctccggg ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac 20400cttctacctc aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg 20460gcccggcaac gaccgcctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg 20520agaggggtac aacgtggccc agtgcaacat gaccaaggac tggttcctgg ttcagatgct 20580ggcccactac aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat 20640gtactccttc ttccgcaact tccagcccat gagccgccag gtcgtggacg aggtcaacta 20700caaggactac caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta 20760cctcgcgccc accatgcgcc agggacagcc ctaccccgcc aactacccct acccgctcat 20820cggcaagagc gccgtcgcca gcgtcaccca gaaaaagttc ctctgcgacc gggtcatgtg 20880gcgcatcccc ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa 20940catgctctac gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga 21000tgagtccacc cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc 21060ccaccgcggc gtcatcgagg ccgtctacct gcgcacgccc ttctcggccg gtaacgccac 21120cacctaagcc ccgctcttgc ttcttgcaag atgacggcct gtgcgggctc cggcgagcag 21180gagctcaggg ccatcctccg cgacctgggc tgcgggccct gcttcctggg caccttcgac 21240aagcgcttcc cgggattcat ggccccgcac aagctggcct gcgccatcgt caacacggcc 21300
ggccgcgaga ccgggggcga gcactggctg gccttcgcct ggaacccgcg ctcccacacc 21360tgctacctct tcgacccctt cgggttctcg aacgagcgcc tcaagcagat ctaccagttc 21420gagtacgagg gcctgctgcg ccgcagcgcc ctggccaccg aggaccgctg cgtcaccctg 21480gaaaagtcca cccagaccgt gcagggtccg cgctcggccg cctgcgggct cttctgctgc 21540atgttcctgc acgccttcgt gcactggccc gaccgcccca tggacaagaa ccccaccatg 21600aacttgctga cgggggtgcc caacggcatg ctccagtcgc cccaggtgga acccaccctg 21660cgccgcaacc aggaagcgct ctaccgcttc ctcaacgccc actccgccta ctttcgctcc 21720caccgcgcgc gcatcgagaa ggccaccgcc ttcgaccgca tgaatcaaga catgtaaacc 21780gtgtgtgtat gtgaatgctt tattcataat aaacagcaca tgtttatgcc accttctctg 21840aggctctgac tttatttaga aatcgaaggg gttctgccgg ctctcggcat gccccgcggg 21900cagggatacg ttgcggaact ggtacttggg cagccacttg aactcgggga tcagcagctt 21960gggcacgggg aggtcgggga acgagtcgct ccacagcttg cgcgtgagtt gcagggcgcc 22020cagcaggtcg ggcgcggaga tcttgaaatc gcagttggga cccgcgttct gcgcgcgaga 22080gttgcggtac acggggttgc agcactggaa caccatcagg gccgggtgct tcacgctcgc 22140cagcaccgtc gcgtcggtga tgccctccac gtccagatcc tcggcgttgg ccatcccgaa 22200gggggtcatc ttgcaggtct gccgccccat gctgggcacg cagccgggct tgtggttgca 22260atcgcagtgc agggggatca gcatcatctg ggcctgctcg gagctcatgc ccgggtacat 22320ggccttcatg aaagcctcca gctggcggaa ggcctgctgc gccttgccgc cctcggtgaa 22380gaagaccccg caggacttgc tagagaactg gttggtggcg cagcccgcgt cgtgcacgca 22440gcagcgcgcg tcgttgttgg ccagctgcac cacgctgcgc ccccagcggt tctgggtgat 22500cttggcccgg tcggggttct ccttcagcgc gcgctgtccg ttctcgctcg ccacatccat 22560ctcgatcgtg tgctccttct ggatcatcac ggtcccgtgc aggcaccgca gcttgctctc 22620ggcctcggtg cacccgtgca gccacagcgc gcagccggtg ctctcccagt tcttgtgggc 22680gatctgggag tgcgagtgca cgaagccctg caggaagcgg cccatcatcg cggtcagggt 22740cttgttgctg gtgaaggtca gcgggatgcc gcggtgctcc tcgttcacat acaggtggca 22800gatgcggcgg tacacctcgc cctgctcggg catcagctgg aaggcggact tcaggtcgct 22860ctccacgcgg taccggtcca tcagcagcgt catgacttcc atgcccttct cccaggccga 22920aacgatcggc aggctcaggg ggttcttcac cgttgtcatc ttagtcgccg ccgccgaggt 22980cagggggtcg ttctcgtcca gggtctcaaa cactcgcttg ccgtccttct cgatgatgcg 23040cacggggggg aagctgaagc ccacggccgc cagctcctcc tcggcctgcc tttcgtcctc 23100gctgtcctgg ctgatgtctt gcaaaggcac atgcttggtc ttgcggggtt tctttttggg 23160cggcagaggc ggcggcggag acgtgctggg cgagcgcgag ttctcgctca ccacgactat 23220ttcttcttct tggccgtcgt ccgagaccac gcggcggtag gcatgcctct tctggggcag 23280aggcggaggc gacgggctct cgcggttcgg cgggcggctg gcagagcccc ttccgcgttc 23340gggggtgcgc tcctggcggc gctgctctga ctgacttcct ccgcggccgg ccattgtgtt 23400
ctcctaggga gcaacaacaa gcatggagac tcagccatcg tcgccaacat cgccatctgc 23460ccccgccgcc gacgagaacc agcagaatga aagcttaacc gccccgccgc ccagccccac 23520ctccgacgcc gcggccccag acatgcaaga gatggaggaa tccatcgaga ttgacctggg 23580ctacgtgacg cccgcggagc acgaggagga gctggcagcg cgcttttcag ccccggaaga 23640gaaccaccaa gagcagccag agcaggaagc agagagcgag cagaaccagg ctgggctcga 23700gcatggcgac tacctgagcg gggcagagga cgtgctcatc aagcatctga cccgccaatg 23760catcatcgtc aaggacgcgc tgctcgaccg cgccgaggtg cccctcagcg tggcggagct 23820cagccgcgcc tacgagcgca acctcttctc gccgcgcgtg ccccccaagc gccagcccaa 23880cggcacctgc gagcccaacc cgcgcctcaa cttctacccg gtcttcgcgg tgcccgaggc 23940cctggccacc taccacctct ttttcaagaa ccaaaggatc cccgtctcct gccgcgccaa 24000ccgcacccgc gccgacgccc tgctcaacct gggccccggc gcccgcctac ctgatatcac 24060ctccttggaa gaggttccca agatcttcga gggtctgggc agcgacgaga ctcgggccgc 24120gaacgctctg caaggaagcg gagaggaaca tgagcaccac agcgccctgg tggagttgga 24180aggcgacaac gcgcgcctgg cggtgctcaa gcgcacggtc gagctgaccc acttcgccta 24240cccggcgctc aacctgcccc ccaaggtcat gagcgccgtc atggaccagg tgctcatcaa 24300gcgcgcctcg cccattgagg acatgcagga ccccgagagc tcggacgagg gcaagcccgt 24360ggtcagcgac gagcagctgg cgcgctggct gggagcgagt agcacccccc agagcctgga 24420agagcggcgc aagctcatga tggccgtggt cctggtgacc gtggagctgg agtgtctgcg 24480ccgcttcttc gccgacgcag agaccctgcg caaggtcgag gagaacctgc actacctctt 24540caggcacggg ttcgtgcgcc aggcctgcaa gatctccaac gtggagctga ccaacctggt 24600ctcctacatg ggcatcctgc acgagaaccg cctggggcag aacgtgctgc acaccaccct 24660gcgcggggag gcccgccgcg actacatccg cgactgcgtc tacctgtacc tctgccacac 24720ctggcagacg ggcatgggcg tgtggcagca gtgcctggag gagcagaacc tgaaagagct 24780ctgcaagctc ctgcagaaga acctcaaggc cctgtggacc gggttcgacg agcgcaccac 24840cgcctcggac ctggccgacc tcatcttccc cgagcgcctg cggctgacgc tgcgcaacgg 24900gctgcccgac tttatgagcc aaagcatgtt gcaaaacttt cgctctttca tcctcgaacg 24960ctccgggatc ctgcccgcca cctgctccgc gctgccctcg gacttcgtgc cgctgacctt 25020ccgcgagtgc cccccgccgc tctggagcca ctgctacttg ctgcgcctgg ccaactacct 25080ggcctaccac tcggacgtga tcgaggacgt cagcggcgag ggtctgctgg agtgccactg 25140ccgctgcaac ctctgcacgc cgcaccgctc cctggcctgc aacccccagc tgctgagcga 25200gacccagatc atcggcacct tcgagttgca aggccccggc gaggagggca aggggggtct 25260gaaactcacc ccggggctgt ggacctcggc ctacttgcgc aagttcgtgc ccgaggacta 25320ccatcccttc gagatcaggt tctacgagga ccaatcccag ccgcccaagg ccgagctgtc 25380ggcctgcgtc atcacccagg gggccatcct ggcccaattg caagccatcc agaaatcccg 25440ccaagaattt ctgctgaaaa agggccacgg ggtctacttg gacccccaga ccggagagga 25500
gctcaacccc agcttccccc aggatgcccc gaggaagcag caagaagctg aaagtggagc 25560tgccgccgcc ggaggatttg gaggaagact gggagagcag tcaggcagag gaggagatgg 25620aagactggga cagcactcag gcagaggagg acagcctgca agacagtctg gaggaggaag 25680acgaggtgga ggaggaggag gcagaggaag aagcagccgc cgccagaccg tcgtcctcgg 25740cggagaaagc aagcagcacg gataccatct ccgctccggg tcggggtcgc ggcggccggg 25800cccacagtag gtgggacgag accgggcgct tcccgaaccc caccacccag accggtaaga 25860aggagcggca gggatacaag tcctggcggg ggcacaaaaa cgccatcgtc tcctgcttgc 25920aagcctgcgg gggcaacatc tccttcaccc ggcgctacct gctcttccac cgcggggtga 25980acttcccccg caacatcttg cattactacc gtcacctcca cagcccctac tactgtttcc 26040aagaagaggc agaaacccag cagcagcaga aaaccagcga cagcggcagc agctagaaaa 26100tccacagcgg caggtggact gaggatcgcg gcgaacgagc cggcgcagac ccgggagctg 26160aggaaccgga tctttcccac cctctatgcc atcttccagc agagtcgggg gcaggagcag 26220gaactgaaag tcaagaaccg ttctctgcgc tcgctcaccc gcagttgtct gtatcacaag 26280agcgaagacc aacttcagcg cactctcgag gacgccgagg ctctcttcaa caagtactgc 26340gcgctcactc ttaaagagta gcccgcgccc gcccacacac ggaaaaaggc gggaattacg 26400tcaccacctg cgcccttcgc ccgaccatca tcatgagcaa agagattccc acgccttaca 26460tgtggagcta ccagccccag atgggtctgg ccgccggcgc cgcccaggac tactccaccc 26520gcatgaactg gctcagtgcc gggcccgcga tgatctcacg ggtgaatgac atccgcgccc 26580atcgaaacca gatactccta gaacagtcag cgatcaccgc cacgccccgc catcacctta 26640atccgcgtaa ttggcccgcc gccctggtgt accaggaaat tccccagccc acgaccgtac 26700tacttccgcg agacgcccag gccgaagtcc agctgactaa ctcaggtgtc cagctggccg 26760gcggcgccgc cctgtgtcgt caccgccccg ctcagggtat aaagcggctg gtgatccgag 26820gcagaggcac acagctcaac gacgaggtgg tgagctcttc gctgggtctg cgacctgacg 26880gagtcttcca actcgccgga tcggggagat cttccttcac gcctcgtcag gccgtcctga 26940ctttggagag ttcgtcctcg cagccccgct cgggcggcat cggcactctc cagttcgtgg 27000aggagttcac tccctcggtc tacttcaacc ccttctccgg ctcccccggc cactacccgg 27060acgagttcat cccgaacttc gacgccatca gcgagtcggt ggacggctac gattgaatgt 27120cccatggtgg cgcagctgac ctagctcggc ttcgacacct ggaccactgc cgccgcttcc 27180gctgcttcgc tcgggatctc gccgagtttg cctactttga gctgcccgag gagcaccctc 27240agggcccggc ccacggagtg cggatcatca tcgaaggggg cctcgactcc cacctgcttc 27300ggatcttcag ccagcgaccg atcctggtcg agcgcgagca aggacagacc cgtctgaccc 27360tgtactgcat ctgcaaccac cccggcctgc atgaaagtct ttgttgtctg ctgtgtactg 27420agtataataa aagctgagat cagcgactac tccggactcg attgtggtgt tcctgctatc 27480aaccggtccc tgttcttcac cgggaacgag accgagctcc agctccagtg taagccccac 27540aagaagtacc tcacctggct gttccagggc tctccgatcg ccgttgtcaa ccactgcgac 27600
aacgacggag tcctgctgag cggccctgcc aaccttactt tttccacccg cagaagcaag 27660ctccagctct tccaaccctt cctccccggg acctatcagt gcgtctcggg accctgccat 27720cacaccttcc acctgatccc gaataccaca gcgccgctcc ccgctactaa caaccaaact 27780acccaccaac gccaccgtcg cgacctttcc tctgaatcta atactaccac ccacaccgga 27840ggtgagctcc gaggtcgacc aacctctggg atttactacg gcccctggga ggtggtgggg 27900ttaatagcgc taggcctagt tgtgggtggg cttttggctc tctgctacct atacctccct 27960tgctgttcgt acttagtggt gctgtgttgc tggtttaaga aatggggaag atcaccctag 28020tgagctgcgg tgtgctggtg gcggtgttgc tttcgattgt gggactgggc ggcgcggctg 28080tagtgaagga ggagaaggcc gatccctgct tgcatttcaa tcccgacaaa tgccagctga 28140gttttcagcc cgatggcaat cggtgcacgg tgctgatcaa gtgcggatgg gaatgtgaga 28200acgtgagaat cgagtacaat aacaagactc ggaacaatac tctcgcgtcc gtgtggcaac 28260ccggggaccc cgagtggtac accgtctctg tccccggtgc tgacggctcc ccgcgcaccg 28320tgaataatac tttcattttt gcgcacatgt gcgacacggt catgtggatg agcaagcagt 28380acgatatgtg gccccccacg aaggagaaca tcgtggtctt ctccatcgct tacagcgtgt 28440gcacggcgct aatcaccgct atcgtgtgcc tgagcattca catgctcatc gctattcgcc 28500ccagaaataa tgccgaaaaa gagaaacagc cataacacgt tttttcacac acctttttca 28560gaccatggcc tctgttactg ccctaattat ttttttgggt ctcgtgggca ctagcagcac 28620ttttcagcat ataaacaaaa ctgtttatgc tggttctaat tctgtattac ctgggcatca 28680atcacaccag aaagtttcat ggtactggta tgataaaaat aacacgccag tcacactctg 28740caagggtcat caaacaccca taaaccgtag tggaattttt tttaaatgta atcataataa 28800tattacacta ctttcaatta caaagcacta ttctggtact tactatggaa ccaattttaa 28860cataaaacag gacacttact atagtgtcac agtattggat ccaactactc ctagaacaac 28920tacaaaaccc acaactacta agaggcacac taaacctaaa actaccaaga aaaccactgt 28980caaaacaaca actaggacca ccacaactac agaggctacc accagcacaa cacttgctgc 29040aactacacac acacacactg agctaacctt acagaccact aatgatttga tagccctgtt 29100gcaaaagggg gataacagca ccacttccga tgaggaaata cccaaatcca tgattggcat 29160tattgttgct gtagtggtgt gcatgttgat catcgccttg tgcatggtgt actatgcctt 29220ctgctacaga aagcacagac tgaacgacaa gctggaacac ttactaagtg ttgaatttta 29280attttttaga accatgaaga tcctaggcct tttagttttt tctatcatta cctctgctct 29340ttgtgaatca gtgaataaag atgttactat taccactggt tctaattata cactgaaagg 29400gccaccctca ggtatgcttt cgtggtattg ctattttgga actgacactg atcaaactga 29460attatgcaat tttcaaaaag gcaaaacctc aaactctaaa atctctaatt atcaatgcaa 29520tggcactgat ctgatactac tcaatgtcac gaaagcatat ggtggcagtt attcttgccc 29580tggacaaaac actgaagaaa tgatttttta caaagtggaa gtggttgatc ccactactcc 29640acccaccacc acaactactc acaccacaca cacagaacaa accacagcag aggaggcagc 29700
aaagttagcc ttgcaggtcc aagacagttc atttgttggc attaccccta cacctgatca 29760gcggtgtccg gggctgctag tcagcggcat tgtcggtgtg ctttcgggat tagcagtcat 29820aatcatctgc atgttcattt ttgcttgctg ctatagaagg ctttaccgac aaaaatcaga 29880cccactgctg aacctctatg tttaattttt tccagagcca tgaaggcagt tagcactcta 29940gttttttgtt ctttgattgg cattgttttt agtgctgggt ttttgaaaaa tcttaccatt 30000tatgaaggtg agaatgccac tctagtgggc atcagtggtc aaaatgtcag ctggctaaaa 30060taccatctag atgggtggaa agacatttgc gattggaatg tcactgtgta tacatgtaat 30120ggagttaacc tcaccattac taatgccacc caagatcaga atggtaggtt taagggtcag 30180agtttcacta gaaataatgg gtatgaatcc cataacatgt ttatctatga cgtcactgtc 30240atcagaaatg agaccgccac caccacacag atgcccacta cacacagttc taccactact 30300accaagcaaa ccacacagac aaccactttt tatacatcaa ctcagcatat gaccaccact 30360acagcagcaa agccaagtag cgcagcgcct cagccacagg ctttggcttt gaaagctgca 30420caacctagta caactactaa gaccaatgag cagactactg attttttgtc cactgtcgag 30480agccacacca cagctacctc cagtgccttc tctagcaccg ccaatctctc ctcgctttcc 30540tctacaccaa tcagtcccgc tactactcct agccccgctc ctcttcccac tcccctgaag 30600caaacagacg gcggcatgca atggcagatc accctgctca ttgtgatcgg gttggtcatc 30660ctggccgtgt tgctctacta catcttctgc cgccgcattc ccaacgcgca ccgcaagccg 30720gtctacaagc ccatcgttgt cgggcagccg gagccgcttc aggtggaagg gggtctaagg 30780aatcttctct tctcttttac agtatggtga ttgaactatg attcctagac aattcttgat 30840cactattctt atctgcctcc tccaagtctg tgccaccctc gctctggtgg ccaacgccag 30900tccagactgt attgggccct tcgcctccta cgtgctcttt gccttcatca cctgcatctg 30960ctgttgtagc atagtctgcc tgcttatcac cttcttccag ttcattgact ggatctttgt 31020gcgcatcgcc tacctgcgcc accaccccca gtaccgcgac cagcgagtgg cgcgactgct 31080caggctcctc tgataagcat gcgggctctg ctacttctcg cgcttctgct gttagtgctc 31140ccccgtcccg tcgacccccg gtcccccgag gaggtccgca aatgcaaatt ccaagaaccc 31200tggaaattcc tcaaatgcta ccgccaaaaa tcagacatgc atcccagctg gatcatgatc 31260attgggatcg tgaacattct ggcctgcacc ctcatctcct ttgtgattta cccctgcttt 31320gactttggtt ggaactcgcc agaggcactc tatctcccgc ctgagcctga cacaccacca 31380cagcagcaac ctcaggcaca cgcactacca ccaccacagc ctaggccaca atacatgccc 31440atattagact atgaggccga gccacagcga cccatgctcc ccgctattag ttacttcaat 31500ctaaccggcg gagatgactg acccactggc caacaacaac gtcaacgacc ttctcctgga 31560catggacggc cgcgcctcgg agcagcgact cgcccaactc cgcatccgcc agcagcagga 31620gagagccgtc aaggagctgc aggatgcggt ggccatccac cagtgcaaga aaggcatctt 31680ctgcctggtg aagcaggcca agatctccta cgaggtcacc cagaccgacc atcgcctctc 31740ctacgagctc ctgcagcagc gccagaagtt cacctgcctg gtcggagtca accccatcgt 31800
catcacccag cagtcgggcg ataccaaggg gtgcatccac tgctcctgcg actcccccga 31860gtgcgttcac accatgatca agaccctctg cggcctccgc gacctcctcc ccatgaacta 31920atcaccccct tatccagtga aataaagatc atattgatga tgatttaaat aaaaaaataa 31980tcatttgatt tgaaataaag atacaatcat attgatgatt tgagtttaac aaaaataaag 32040aatcacttac ttgaaatctg ataccaggtc tctgtccatg ttttctgcca acaccacctc 32100actcccctct tcccagctct ggtactgcag gccccggcgg gctgcaaact tcctccacac 32160gctgaagggg atgtcaaatt cctcctgtcc ctcaatcttc attttctctt ctatcagatg 32220tccaaaaagc gcgcgcgggt ggatgatgac ttcgaccccg tgtaccccta cgatgcagac 32280aacgcaccga ctgtgccctt catcaaccct cccttcgtct cttcagatgg attccaagaa 32340aagcccctgg gggtgttgtc cctgcgactg gccgatcccg tcaccaccaa gaacggggct 32400gtcaccctca agctggggga gggggtggac ctcgacgact cgggaaaact catctccaaa 32460aatgccacca aggccactgc ccctctcagt atttccaaca acaccatttc ccttaacatg 32520gatacccctc tttacaacaa caatggaaag ctaggtatga aggtaaccgc accattaaag 32580atattagaca cagatctact aaaaacactt gttgttgctt atgggcaggg attaggaaca 32640aacaccaatg gtgctcttgt tgcccaacta gcatacccac ttgtttttaa taccgctagc 32700aaaattgccc ttaatttagg caatggacca ttaaaagtgg atgcaaatag actgaacatt 32760aattgcaaaa gaggtatcta tgtcactacc acaaaagatg cactggagat taatatcagt 32820tgggcaaatg ctatgacatt tataggaaat gccattggtg tcaatattga cacaaaaaaa 32880ggcctacagt tcggcacttc aagcactgaa acagatgtta aaaatgcttt tccactccaa 32940gtaaaacttg gagctggtct tacatttgac agcacaggtg ccattgttgc ttggaacaaa 33000gaagatgaca aacttacact gtggaccaca gccgatccat ctccaaactg tcacatatat 33060tctgcaaagg atgctaagct tacactctgc ttgacaaagt gtggtagtca gatactgggc 33120actgtttctc tcatagctgt tgatactggt agcttaaatc caataacagg aaaagtaacc 33180actgctcttg tttcacttaa attcgatgcc aatggagttt tgcaagccag ttcaacacta 33240gataaagaat attggaattt cagaaaagga gatgtgacac ctgctgaccc ctacactaat 33300gctataggct ttatgcccaa ccttaatgca tacccaaaaa acacaaacgc agctgcaaaa 33360agtcacattg ttggaaaagt atacctacat ggggatgaaa gcaagccact agacttgata 33420attacattta atgaaaccag tgatgaatcc tgtacttatt gcattaactt tcagtggcag 33480tggggaactg accaatataa agatgaaaca cttgcagtca gttcattcac cttctcatac 33540attgctaaag aataacatcc accctgcatg ccaacccatt tccctctatc tatacatgga 33600aaactctgaa gcagaaaaaa taaagttcaa gtgttttatt gattcaacag tttttacaga 33660attcgagtag ttattttccc tccaccctcc caactcatgg aatacaccat cctctcccca 33720cgcacagcct taaacatctg aatgccattg gtaatggaca tggttttggc ctccacattc 33780cacacagttt cagagcgagc cagtctcggg tcggtcaggg agatgaaacc ctccgggcac 33840tcctgcatct gcacctcaca gttcaacagc tgagggctgt cctcggtggt cgggatcaca 33900
gttatctgga agaagagcga tgagagtcat aatccgcgaa cgggatcggg cggttgtggc 33960gcatcaggcc ccgcagcagt cgctgtctgc gccgctccgt caagctgctg ctcaaggggt 34020ccgggtccag ggactccccg cgcatgatgc cgatggccct gagcatcagt cgcctggtgc 34080ggcgggcgca gcagcggatg cggatctcac tcaggtcgga acagtacgtg cagcacagca 34140ctaccaagtt gttcaacagt ccatagttca acgtgctcca gccaaaactc atctgtggaa 34200ctatgctgcc cacatgtcca tcgtaccaga tcctgatgta aatcaggtgg cgccccctcc 34260agaacacact gcccatgtac atgatctcct tgggcatgtg caggttcacc acctcccggt 34320accacatcac ccgctggttg aacatgcagc cccggatgat cctgcggaac cacagggcca 34380gcaccgcccc gcccgccatg cagcgcaggg accccgggtc ctggcaatgg cagtggatga 34440tccaccgctc gtacccgtgg atcatctggg agctgaacaa gtctatgttg gcacagcaca 34500ggcacacgct catgcatctc ttcagcactc tcagctcctc gggggtcaaa accatatccc 34560agggtacggg gaactcttgc aggacagcga accccgcaga acagggcaaa cctcgcacag 34620aacttacatt gtgcatggac agggtatcgc aatcaggcag caccgggtga tcctccacca 34680gggaagcgcg ggtctcgatt tcctcacagc gtggtaaggg ggccggtcga tacgggtgat 34740ggcgggacgc ggctgatcgt gttcgcgatc gtgtcatgat gcagttgctt tcggacattt 34800tcgtacttgc tatagcagaa cctggtccgg gcgctgcaca ccgatcgccg gcggcggtct 34860cggcgcttgg aacgctccgt gttgaaattg taaaacagcc actctctcag accgtgcagc 34920agatctaggg cctcaggagt gatgaagatc ccatcatgcc tgatggctct gatcacatcg 34980accaccgtgg aatgggccag acccagccag atgatgcaat tttgttgggt ttcggtgacg 35040gcgggggagg gaagaacagg aagaaccatg attaacttta atccaaacgg tctcggagca 35100cttcaaaatg aaggtcgcgg agatggcacc tctcgccccc gctgtgttgg tggaaaataa 35160cagccaggtc aaaggtgata cggttctcga gatgttccac ggtggcttcc agcaaagcct 35220ccacgcgcac atccagaaac aagacaatag cgaaagcggg agggttctct aattcctcaa 35280tcatcatgtt acactcctgc accatcccca gataattttc atttttccag ccttgaatga 35340ttcgaactag ttcctgaggt aaatccaagc cagccatgat aaagagctcg cgcagagcgc 35400cctccaccgg cattcttaag cacaccctca taattccaag atattctgct cctggttcac 35460ctgcagcaga ttgacaagcg gaatatcaaa ctctctgccg cgatccctaa gctcctccct 35520cagcaataac tgtaagtact ctctcatatc ctctccgaaa tttttagcca taggaccgcc 35580aggaataaga ttagggcaag ccacagtaca gataaaccga agtcctcccc agtgagcatt 35640gccaaatgca agactgctat aagcatgctg gctagacccg gtgatatctt ccagataatt 35700ggacagaaaa tcgcccaggc aatttttaag aaaatcaaca aaagaaaaat cctccaggtg 35760cacgtttaga gcctcgggaa caacgatgga gtaaatgcaa gcggtgcgtt ccagcatggt 35820tagttagctg atctgtagaa aaaacaaaaa tgaacattaa accatgctag cctggcgaac 35880aggtgggtaa atcgttcttt ccagcaccag gcaggccacg gggtctccgg cgcgaccctc 35940gtaaaaattg tcgctatgat tgaaaaccat cacagagaga cgttcccggt ggccggcgtg 36000
aatgattcga caagacgaat acacccccgg aacattggcg tccgcgagtg aaaaaaagcg 36060cccgaggaag caataaggca ctacaatgct cagtctcaag tccagcaaag cgatgccatg 36120cggatgaagc acaaaattct caggtgcgta caaaatgtaa ttactcccct cctgcacagg 36180cagcaaagcc cccgatccct ccaggtacac atacaaagcc tcagcgtcca tagcttaccg 36240agcagcagcg gcacacaaca ggcgcaaaag tcagagaaag gctgagagct ctaacctgtc 36300cacccgctct ctgctcaata tatagcccag atctacactg acgtaaaggc caaagtctaa 36360aaatacccgc caaataatca cacacgccca gcacacgccc agaaaccggt gacacactca 36420gaaaaatacg cgcacttcct caaacgccca aactgccgtc atttccgggt tcccacgcta 36480cgtcatcaaa attcaacttt caaattccgt cgaccgttaa aaacgtcacc cgccccgccc 36540ctaacggtcg ccgctcccgc agccaatcag cgccccgcat ccccaaattc aaacggctca 36600tttgcatatt aacgcgcacc aaaagtttga ggtatattat tgatgatg 36648210321136606212DNA213黑猩猩Pan 6(CV32)基因組4003catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agctgtttga 60atttggggag ggaggaaggt gattggctgc gggagcggcg accgttaggg gcggggcggg 120tgacgttttg atgacgtggc tatgaggcgg agccggtttg caagttctcg tgggaaaagt 180gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600gtaatgtttt cctggctact gggaacgaga ttctggaatt ggtggtggac gccatgatgg 660gtgacgaccc tccagagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720atctggaggt ggatgtgccc gagagcgacc ctaacgagga ggcggtgaat gatttgttta 780gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960aggaggcgat tcgagctgcg gtgaaccagg gagtgaaaac tgcgggcgag agctttagcc 1020
tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140acagtaagtg tgattaactt tagttgggaa ggcagagggt gactgggtgc tgactggttt 1200atttatgtat atgttttttt atgtgtaggt cccgtctctg acgtagatga gacccccact 1260tcagagtgca tttcatcacc cccagaaatt ggcgaggaac cgcccgaaga tattattcat 1320agaccagttg cagtgagagt caccgggcgg agagcagctg tggagagttt ggatgacttg 1380ctacagggtg gggatgaacc tttggacttg tgtacccgga aacgccccag gcactaagtg 1440ccacacatgt gtgtttactt aaggtgatgt cagtatttat agggtgtgga gtgcaataaa 1500atccgtgttg actttaagtg cgtgttttat gactcagggg tggggactgt gggtatataa 1560gcaggtgcag acctgtgtgg tcagttcaga gcaggactca tggagatctg gactgtcttg 1620gaagactttc accagactag acagttgcta gagaactcat cggagggagt ctcttacctg 1680tggagattct gcttcggtgg gcctctagct aagctagtct atagggccaa acaggattat 1740aaggaacaat ttgaggatat tttgagagag tgtcctggta tttttgactc tctcaacttg 1800ggccatcagt ctcactttaa ccagagtatt ctgagagccc ttgacttttc tactcctggc 1860agaactaccg ccgcggtagc cttttttgcc tttattcttg acaaatggag tcaagaaacc 1920catttcagca gggattaccg tctggactgc ttagcagtag ctttgtggag aacatggagg 1980tgccagcgcc tgaatgcaat ctccggctac ttgccagtac agccggtaga cacgctgagg 2040atcctgagtc tccagtcacc ccaggaacac caacgccgcc agcagccgca gcaggagcag 2100cagcaagagg aggaccgaga agagaacccg agagccggtc tggaccctcc ggtggcggag 2160gaggaggagt agctgacttg tttcccgagc tgcgccgggt gctgactagg tcttccagtg 2220gacgggagag ggggattaag cgggagaggc atgaggagac tagccacaga actgaactga 2280ctgtcagtct gatgagccgc aggcgcccag aatcggtgtg gtggcatgag gtgcagtcgc 2340aggggataga tgaggtctcg gtgatgcatg agaaatattc cctagaacaa gtcaagactt 2400gttggttgga gcccgaggat gattgggagg tagccatcag gaattatgcc aagctggctc 2460tgaagccaga caagaagtac aagattacca aactgattaa tatcagaaat tcctgctaca 2520tttcagggaa tggggccgag gtggagatca gtacccagga gagggtggcc ttcagatgtt 2580gtatgatgaa tatgtacccg ggggtggtgg gcatggaggg agtcaccttt atgaacacga 2640ggttcagggg tgatgggtat aatggggtgg tctttatggc caacaccaag ctgacagtgc 2700acggatgctc cttctttggc ttcaataaca tgtgcatcga ggcctggggc agtgtttcag 2760tgaggggatg cagcttttca gccaactgga tgggggtcgt gggcagaacc aagagcaagg 2820tgtcagtgaa gaaatgcctg ttcgagaggt gccacctggg ggtgatgagc gagggcgaag 2880ccaaagtcaa acactgcgcc tctaccgaga cgggctgctt tgtgctgatc aagggcaatg 2940cccaagtcaa gcataacatg atctgtgggg cctcggatga gcgcggctac cagatgctga 3000cctgcgccgg tgggaacagc catatgctgg ccaccgtgca tgtggcctcg cacccccgca 3060agacatggcc cgagttcgag cacaacgtca tgacccgctg caatgtgcac ctgggctccc 3120
gccgaggcat gttcatgccc taccagtgca acatgcaatt tgtgaaggtg ctgctggagc 3180ccgatgccat gtccagagtg agcctgacgg gggtgtttga catgaatgtg gagctgtgga 3240aaattctgag atatgatgaa tccaagacca ggtgccgggc ctgcgaatgc ggaggcaagc 3300acgccaggct tcagcccgtg tgtgtggagg tgacggagga cctgcgaccc gatcatttgg 3360tgttgtcctg caacgggacg gagttcggct ccagcgggga agaatctgac tagagtgagt 3420agtgtttggg gctgggtgtg agcctgcatg aggggcagaa tgactaaaat ctgtggtttt 3480ctgtgtgttg cagcagcatg agcggaagcg cctcctttga gggaggggta ttcagccctt 3540atctgacggg gcgtctcccc tcctgggcgg gagtgtgtca gaatgttatg gnatccacgg 3600tggacggccg gcccgtgcag cccgcgaact cttcaaccct gacctacgcg accctgagct 3660cctcgtccgt ggacgcagct gccgccgcag ctgctgcttc cgccgccagc gccgtgcgcg 3720gaatggccct gggcgccggc tactacagct ctctggtggc caactcgagt tccaccaata 3780atcccgccag cctgaacgag gagaagctgc tgctgctgat ggcccagctc gaggccctga 3840cccagcgcct gggcgagctg acccagcagg tggctcagct gcaggcggag acgcgggccg 3900cggttgccac ggtgaaaacc aaataaaaaa tgaatcaata aataaacgga gacggttgtt 3960gattttaaca cagagtcttg aatctttatt tgatttttcg cgcgcggtag gccctggacc 4020accggtctcg atcattgagc acccggtgga tcttttccag gacccggtag aggtgggctt 4080ggatgttgag gtacatgggc atgagcccgt cccgggggtg gaggtagctc cattgcaggg 4140cctcgtgctc ggggatggtg ttgtaaatca cccagtcata gcaggggcgc agggcgtggt 4200gctgcacgat gtccttgagg aggagactga tggccacggg cagccccttg gtgtaggtgt 4260tgacgaacct gttgagctgg gagggatgca tgcgggggga gatgagatgc atcttggcct 4320ggatcttgag attggcgatg ttcccgccca gatcccgccg ggggttcatg ttgtgcagga 4380ccaccagcac ggtgtatccg gtgcacttgg ggaatttgtc atgcaacttg gaagggaagg 4440cgtgaaagaa tttggagacg cccttgtgac cgcccaggtt ttccatgcac tcatccatga 4500tgatggcgat gggcccgtgg gcggcggcct gggcaaagac gtttcggggg tcggacacat 4560cgtagttgtg gtcctgggtg agctcgtcat aggccatttt aatgaatttg gggcggaggg 4620tgcccgactg ggggacgaag gtgccctcga tcccgggggc gtagttgccc tcgcagatct 4680gcatctccca ggccttgagc tcggaggggg ggatcatgtc cacctgcggg gcgatgaaaa 4740aaacggtttc cggggcgggg gagatgagct gggccgaaag caggttccgg agcagctggg 4800acttgccgca accggtgggg ccgtagatga ccccgatgac cggctgcagg tggtagttga 4860gggagagaca gctgccgtcc tcgcggagga ggggggccac ctcgttcatc atctcgcgca 4920catgcatgtt ctcgcgcacg agttccgcca ggaggcgctc gccccccagc gagaggagct 4980cttgcagcga ggcgaagttt ttcagcggct tgagtccgtc ggccatgggc attttggaga 5040gggtctgttg caagagttcc agacggtccc agagctcggt gatgtgctct agggcatctc 5100gatccagcag acctcctcgt ttcgcgggtt ggggcgactg cgggagtagg gcaccaggcg 5160atgggcgtcc agcgaggcca gggtccggtc cttccagggc cgcagggtcc gcgtcagcgt 5220
ggtctccgtc acggtgaagg ggtgcgcgcc gggctgggcg cttgcgaggg tgcgcttcag 5280gctcatccgg ctggtcgaga accgctcccg gtcggcgccc tgcgcgtcgg ccaggtagca 5340attgagcatg agttcgtagt tgagcgcctc ggccgcgtgg cccttggcgc ggagcttacc 5400tttggaagtg tgtccgcaga cgggacagag gagggacttg agggcgtaga gcttgggggc 5460gaggaagacg gactcggggg cgtaggcgtc cgcgccgcag ctggcgcaga cggtctcgca 5520ctccacgagc caggtgaggt cggggcggtt ggggtcaaaa acgaggtttc ctccgtgctt 5580tttgatgcgt ttcttacctc tggtctccat gagctcgtgt ccccgctggg tgacaaagag 5640gctgtccgtg tccccgtaga ccgactttat gggccggtcc tcgagcgggg tgccgcggtc 5700ctcgtcgtag aggaaccccg cccactccga gacgaaggcc cgggtccagg ccagcacgaa 5760ggaggccacg tgggaggggt agcggtcgtt gtccaccagc gggtccacct tctccagggt 5820atgcaagcac atgtccccct cgtccacatc caggaaggtg attggcttgt aagtgtaggc 5880cacgtgaccg ggggtcccgg ccgggggggt ataaaagggg gcgggcccct gctcgtcctc 5940actgtcttcc ggatcgctgt ccaggagcgc cagctgttgg ggtaggtatt ccctctcgaa 6000ggcgggcatg acctcggcac tcaggttgtc agtttctaga aacgaggagg atttgatatt 6060gacggtgccg ttggagacgc ctttcatgag cccctcgtcc atttggtcag aaaagacgat 6120ctttttgttg tcgagcttgg tggcgaagga gccgtagagg gcgttggaga gcagcttggc 6180gatggagcgc atggtctggt tcttttcctt gtcggcgcgc tccttggcgg cgatgttgag 6240ctgcacgtac tcgcgcgcca cgcacttcca ttcggggaag acggtggtga gctcgtcggg 6300cacgattctg acccgccagc cgcggttgtg cagggtgatg aggtccacgc tggtggccac 6360ctcgccgcgc aggggctcgt tggtccagca gaggcgcccg cccttgcgcg agcagaaggg 6420gggcagcggg tccagcatga gctcgtcggg ggggtcggcg tccacggtga agatgccggg 6480caggagctcg gggtcgaagt agctgatgca ggtgcccaga ttgtccagcg ccgcttgcca 6540gtcgcgcacg gccagcgcgc gctcgtaggg gctgaggggc gtgccccagg gcatggggtg 6600cgtgagcgcg gaggcgtaca tgccgcagat gtcgtagacg tagaggggct cctcgaggac 6660gccgatgtag gtggggtagc agcgcccccc gcggatgctg gcgcgcacgt agtcgtacag 6720ctcgtgcgag ggcgcgagga gccccgtgcc gaggttggag cgttgcggct tttcggcgcg 6780gtagacgatc tggcggaaga tggcgtggga gttggaggag atggtgggcc tttggaagat 6840gttgaagtgg gcgtggggca ggccgaccga gtccctgatg aagtgggcgt aggagtcctg 6900cagcttggcg acgagctcgg cggtgacgag gacgtccagg gcgcagtagt cgagggtctc 6960ttggatgatg tcatacttga gctggccctt ctgcttccac agctcgcggt tgagaaggaa 7020ctcttcgcgg tccttccagt actcttcgag ggggaacccg tcctgatcgg cacggtaaga 7080gcccaccatg tagaactggt tgacggcctt gtaggcgcag cagcccttct ccacggggag 7140ggcgtaagct tgcgcggcct tgcgcaggga ggtgtgggtg agggcgaagg tgtcgcgcac 7200catgaccttg aggaactggt gcttgaagtc gaggtcgtcg cagccgccct gctcccagag 7260ttggaagtcc gtgcgcttct tgtaggcggg gttaggcaaa gcgaaagtaa catcgttgaa 7320
gaggatcttg cccgcgcggg gcatgaagtt gcgagtgatg cggaaaggct ggggcacctc 7380ggcccggttg ttgatgacct gggcggcgag gacgatctcg tcgaagccgt tgatgttgtg 7440cccgacgatg tagagttcca cgaatcgcgg gcggcccttg acgtggggca gcttcttgag 7500ctcgtcgtag gtgagctcgg cggggtcgct gagcccgtgc tgctcgaggg cccagtcggc 7560gacgtggggg ttggcgctga ggaaggaagt ccagagatcc acggccaggg cggtctgcaa 7620gcggtcccgg tactgacgga actgttggcc cacggccatt ttttcggggg tgacgcagta 7680gaaggtgcgg gggtcgccgt gccancggtc ccacttgagc tggagggcga ggtcgtgggc 7740gagctcgacg agcggcgggt ccccggagag tttcatgacc agcatgaagg ggacgagctg 7800cttgccgaag gaccccatcc aggtgtaggt ttccacatcg taggtgagga agagcctttc 7860ggtgcgagga tgcgagccga tggggaagaa ctggatctcc tgccaccagt tggaggaatg 7920gctgttgatg tgatggaagt agaaatgccg acggcgcgcc gagcactcgt gcttgtgttt 7980atacaagcgt ccgcagtgct cgcaacgctg cacgggatgc acgtgctgca cgagctgtac 8040ctgggttcct ttggcgagga atttcagtgg gcagtggagc gctggcggct gcatctcgtg 8100ctgtactacg tcttggccat cggcgtggcc atcgtctgcc tcgatggtgg tcatgctgac 8160gagcccgcgc gggaggcagg tccagacctc ggctcggacg ggtcggagag cgaggacgag 8220ggcgcgcagg ccggagctgt ccagggtcct gagacgctgc ggagtcaggt cagtgggcag 8280cggcggcgcg cggttgactt gcaggagctt ttccagggcg cgcgggaggt ccagatggta 8340cttgatctcc acggcgccgt tggtggctac gtccacggct tgcagggtgc cgtgcccctg 8400gggcgccacc accgtgcccc gtttcttctt gggcgctgct tccatgtcgg tcagaagcgg 8460cggcgaggac gcgcgccggg cggcaggggc ggctcggggc ccggaggcag gggcggcagg 8520ggcacgtcgg cgccgcgcgc gggcaggttc tggtactgcg cccggagaag actggcgtga 8580gcgacgacgc gacggttgac gtcctggatc tgacgcctct gggtgaaggc cacgggaccc 8640gtgagtttga acctgaaaga gagttcgaca gaatcaatct cggtatcgtt gacggcggcc 8700tgccgcagga tctcttgcac gtcgcccgag ttgtcctggt aggcgatctc ggtcatgaac 8760tgctcgatct cctcctcctg aaggtctccg cggccggcgc gctcgacggt ggccgcgagg 8820tcgttggaga tgcggcccat gagctgcgag aaggcgttca tgccggcctc gttccagacg 8880cggctgtaga ccacggctcc gtcggggtcg cgcgcgcgca tgaccacctg ggcgaggttg 8940agctcgacgt ggcgcgtgaa gaccgcgtag ttgcagaggc gctggtagag gtagttgagc 9000gtggtggcga tgtgctcggt gacgaagaag tacatgatcc agcggcggag cggcatctcg 9060ctgacgtcgc ccagggcttc caagcgttcc atggcctcgt agaagtccac ggcgaagttg 9120aaaaactggg agttgcgcgc cgagacggtc aactcctcct ccagaagacg gatgagctcg 9180gcgatggtgg cgcgcacctc gcgctcgaag gccccggggg gctcctcttc catctcctcc 9240tcttcctcct ccactaacat ctcttctact tcctcctcag gaggcggtgg cgggggaggg 9300gccctgcgtc gccggcggcg cacgggcaga cggtcgatga agcgctcgat ggtctccccg 9360cgccggcgac gcatggtctc ggtgacggcg cgcccgtcct cgcggggccg cagcatgaag 9420
acgccgccgc gcatctccag gtggccgccg ggggggtctc cgttgggcag ggagagggcg 9480ctgacgatgc atcttatcaa ttgacccgta gggactccgc gcaaggacct gagcgtctcg 9540agatccacgg gatccgaaaa ccgctgaacg aaggcttcga gccagtcgca gtcgcaaggt 9600aggctgagcc cggtttcttg ttcttcgggt atttggtcgg gaggcggcgg gcgatgctgc 9660tggtgatgaa gttgaagtag gcggtcctga gacggcggat ggtggcgagg agcaccaggt 9720ccttgggccc ggcttgctgg atgcgcagac ggtcggccat gccccaggcg tggtcctgac 9780acctggcgag gtccttgtag tagtcctgca tgagccgctc cacgggcacc tcctcctcgc 9840ccgcgcggcc gtgcatgcgc gtgagcccga acccgcgctg cggctggacg agcgccaggt 9900cggcgacgac gcgctcggtg aggatggcct gctggatctg ggtgagggtg gtctggaagt 9960cgtcgaagtc gacgaagcgg tggtaggctc cggtgttgat ggtgtaggag cagttggcca 10020tgacggacca gttgacggtc tggtggccgg gtcgcacgag ctcgtggtac ttgaggcgcg 10080agtaggcgcg cgtgtcgaag atgtagtcgt tgcaggcgcg cacgaggtac tggtatccga 10140cgaggaagtg cggcggcggc tggcggtaga gcggccatcg ctcggtggcg ggggcgccgg 10200gcgcgaggtc ctcgagcatg aggcggtggt agccgtagat gtacctggac atccaggtga 10260tgccggcggc ggtggtggag gcgcgcggga actcgcggac gcggttccag atgttgcgca 10320gcggcaggaa gtagttcatg gtggccgcgg tctggcccgt gaggcgcgcg cagtcgtgga 10380tgctctagac atacgggcaa aaacgaaagc ggtcagcggc tcgactccgt ggcctggagg 10440ctaagcgaac gggttgggct gcgcgtgtac cccggttcga atctcgaatc aggctggagc 10500cgcagctaac gtggtactgg cactcccgtc tcgacccaag cctgctaacg aaacctccag 10560gatacggagg cgggtcgttt tttggccttg gtcgctggtc atgaaaaact agtaagcgcg 10620gaaagcggcc gcccgcgatg gctcgctgcc gtagtctgga gaaagaatcg ccagggttgc 10680gttgcggtgt gccccggttc gagcctcagc gctcggcgcc ggccggattc cgcggctaac 10740gtgggcgtgg ctgccccgtc gtttccaaga ccccttagcc agccgacttc tccagttacg 10800gagcgagccc ctcttttttt ttcttgtgtt tttgccagat gcatcccgta ctgcggcaga 10860tgcgccccca ccctccacca caaccgcccc taccgcagca gcagcaacag ccggcgcttc 10920tgcccccgcc ccagcagcag ccagccacta ccgcggcggc cgccgtgagc ggagccggcg 10980ttcagtatga cctggccttg gaagagggcg aggggctggc gcggctgggg gcgtcgtcgc 11040cggagcggca cccgcgcgtg cagatgaaaa gggacgctcg cgaggcctac gtgcccaagc 11100agaacctgtt cagagacagg agcggcgagg agcccgagga gatgcgcgcc tcccgcttcc 11160acgcggggcg ggagctgcgg cgcggcctga accgaaagcg ggtgctgagg gacgaggatt 11220tcgaggcgga cgagctgacg gggatcagcc ccgtgcgcgc gcacgtggtc gnggncaacc 11280tggtcacggc gtacgagcag accgtgaagg aggagagcaa cttccaaaaa tccttcaaca 11340accacgtgcg caccttgatc gcgcgcgagg aggtgaccct gggcctgatg cacctgtggg 11400acctgctgga ggccatcgtg cagaacccca cgagcaagcc gctgacggcg cagctgtttc 11460tggtggtgca gcacagtcgg gacaacgaga cgttcaggga ggcgctgctg aatatcaccg 11520
agcccgaggg ccgctggctc ctggacctgg tgaacatttt gcagagcatc gtggtgcagg 11580agcgcgggct gccgctgtcc gagaagctgg cggccatcaa cttctcggtg ctgagtctgg 11640gcaagtacta cgctaggaag atctacaaga ccccgtacgt gcccatagac aaggaggtga 11700agatcgacgg gttttacatg cgcatgaccc tgaaagtgct gaccctgagc gacgatctgg 11760gggtgtaccg caacgacagg atgcaccgcg cggtgagcgc cagccgccgg cgcgagctga 11820gcgaccagga gctgatgcac agcctgcagc gggccctgac cggggccggg accgaggggg 11880agagctactt tgacatgggc gcggacctgc gctggcagcc cagccgccgg gccttggaag 11940ctgccggcgg ttccccctac gtggaggagg tggacgatga ggaggaggag ggcgagtacc 12000tggaagactg atggcgcgac cgtatttttg ctagatgcag caacagccac cgccgccgcc 12060tcctgatccc gcgatgcggg cggcgctgca gagccagccg tccggcatta actcctcgga 12120cgattggacc caggccatgc aacgcatcat ggcgctgacg acccgcaatc ccgaagcctt 12180tagacagcag cctcaggcca accggctctc ggccatcctg gaggccgtgg tgccctcgcg 12240ctcgaacccc acgcacgaga aggtgctggc catcgtgaac gcgctggtgg agaacaaggc 12300catccgcggt gacgaggccg ggctggtgta caacgcgctg ctggagcgcg tggcccgcta 12360caacagcacc aacgtgcaga cgaacctgga ccgcatggtg accgacgtgc gcgaggcggt 12420gtcgcagcgc gagcggttcc accgcgagtc gaacctgggc tccatggtgg cgctgaacgc 12480cttcctgagc acgcagcccg ccaacgtgcc ccggggccag gaggactaca ccaacttcat 12540cagcgcgctg cggctgatgg tggccgaggt gccccagagc gaggtgtacc agtcggggcc 12600ggactacttc ttccagacca gtcgccaggg cttgcagacc gtgaacctga gccaggcttt 12660caagaacttg cagggactgt ggggcgtgca ggccccggtc ggggaccgcg cgacggtgtc 12720gagcctgctg acgccgaact cgcgcctgct gctgctgctg gtggcgccct tcacggacag 12780cggcagcgtg agccgcgact cgtacctggg ctacctgctt aacctgtacc gcgaggccat 12840cggacaggcg cacgtggacg agcagaccta ccaggagatc acccacgtga gccgcgcgct 12900gggccaggag gacccgggca acctggaggc caccctgaac ttcctgctga ccaaccggtc 12960gcagaagatc ccgccccagt acgcgctgag caccgaggag gagcgcatcc tgcgctacgt 13020gcagcagagc gtggggctgt tcctgatgca ggagggggcc acgcccagcg cggcgctcga 13080catgaccgcg cgcaacatgg agcccagcat gtacgcccgc aaccgcccgt tcatcaataa 13140gctgatggac tacttgcatc gggcggccgc catgaactcg gactacttta ccaacgccat 13200cttgaacccg cactggctcc cgccgcccgg gttctacacg ggcgagtacg acatgcccga 13260ccccaacgac gggttcctgt gggacgacgt ggacagcagc gtgttctcgc cgcgtccagg 13320aaccaatgcc gtgtggaaga aagagggcgg ggaccggcgg ccgtcctcgg cgctgtccgg 13380tcgcgcgggt gctgccgcgg cggtgcccga ggccgccagc cccttcccga gcctgccctt 13440ttcgctgaac agcgtgcgca gcagcgagct gggtcggctg acgcgaccgc gcctgctggg 13500cgaggaggag tacctgaacg actccttgtt gaggcccgag cgcgagaaga acttccccaa 13560taacgggata gagagcctgg tggacaagat gagccgctgg aagacgtacg cgcacgagca 13620
cagggacgag ccccgagcta gcagcgcagg cacccgtaga cgccagcggc acgacaggca 13680gcggggactg gtgtgggacg atgaggattc cgccgacgac agcagcgtgt tggacttggg 13740tgggagtggt ggtaacccgt tcgctcacct gcgcccccgt atcgggcgcc tgatgtaaga 13800atctgaaaaa ataaaagacg gtactcacca aggccatggc gaccagcgtg cgttcttctc 13860tgttgtttgt agtagtatga tgaggcgcgt gtacccggag ggtcctcctc cctcgtacga 13920gagcgtgatg cagcaggcgg tggcggcggc gatgcagccc ccgctggagg cgccttacgt 13980gcccccgcgg tacctggcgc ctacggaggg gcggaacagc attcgttact cggagctggc 14040acccttgtac gataccaccc ggttgtacct ggtggacaac aagtcggcag acatcgcctc 14100gctgaactac cagaacgacc acagcaactt cctgaccacc gtggtgcaga acaacgattt 14160cacccccacg gaggccagca cccagaccat caactttgac gagcgctcgc ggtggggcgg 14220ccagctgaaa accatcatgc acaccaacat gcccaacgtg aacgagttca tgtacagcaa 14280caagttcaag gcgcgggtga tggtctcgcg caagaccccc aacggggtgg atgatgatta 14340tgatggtagt caggacgagc tgacctacga gtgggtggag tttgagctgc ccgagggcaa 14400cttctcggtg accatgacca tcgatctgat gaacaacgcc atcatcgaca actacttggc 14460ggtggggcgg cagaacgggg tgctggagag cgacatcggc gtgaagttcg acacgcgcaa 14520cttccggctg ggctgggacc ccgtgaccga gctggtgatg ccgggcgtgt acaccaacga 14580ggccttccac cccgacatcg tcctgctgcc cggctgcggc gtggacttca ccgagagccg 14640cctcagcaac ctgctgggca tccgcaagcg gcagcccttc caggagggct tccagatcct 14700gtacgaggac ctggaggggg gcaacatccc cgcgctcttg gatgtcgaag cctacgagaa 14760aagcaaggag gatagcaccg ccgcggcgac cgcagccgtg gccaccgcct ctaccgaggt 14820gcggggcgat aattttgcta gcgctgcggc agcggccgag gcggctgaaa ccgaaagtaa 14880gatagtcatc cagccggtgg agaaggacag caaggacagg agctacaacg tgctcgcgga 14940caagaaaaac accgcctacc gcagctggta cctggcctac aactacggcg accccgagaa 15000gggcgtgcgc tcctggacgc tgctcaccac ctcggacgtc acctgcggcg tggagcaagt 15060ctactggtcg ctgcccgaca tgatgcaaga cccggtcacc ttccgctcca cgcgtcaagt 15120tagcaactac ccggtggtgg gcgccgagct cctgcccgtc tactccaaga gcttcttcaa 15180cgagcaggcc gtctactcgc agnagctgcg cgccttcacc tcgctcacgc acgtcttcaa 15240ccgcttcccc gagaaccaga tcctcgtccg ccgccgcgcc caccattacc accgtcagtg 15300aaaacgttcc tgctctcaca gatcacggga ccctgccgct gcgcagcagt atccggggag 15360tccagcgcgt gaccgtcact gacgccagac gccgcacctg cccctacgtc tacaaggccc 15420tgggcgtagt cgcgccgcgc gtcctctcga gccgcacctt ctaaaaaatg tccattctca 15480tctcgcccag taataacacc ggttggggcc tgcgcgcgcc cagcaagatg tacggaggcg 15540ctcgccaacg ctccacgcaa caccccgtgc gcgtgcgcgg gcacttccgc gctccctggg 15600gcgccctcaa gggccgcgtg cgctcgcgca ccaccgtcga cgacgtgatc gaccaggtgg 15660tggccgacgc gcgcaactac acgcccgccg ccgcgcccgt ctccaccgtg gacgccgtca 15720
tcgacagcgt ggtggccgac gcgcgccggt acgcccgcac caagagccgg cggcggcgca 15780tcgcccggcg gcaccggagc acccccgcca tgcgcgcggc gcgagccttg ctgcgcaggg 15840ccaggcgcac gggacgcagg gccatgctca gggcggccag acgcgcggcc tccggcagca 15900gcagcgccgg caggacccgc agacgcgcgg ccacggcggc ggcggcggcc atcgccagca 15960tgtcccgccc gcggcgcggc aacgtgtact gggtgcgcga cgccgccacc ggtgtgcgcg 16020tgcccgtgcg cacccgcccc cctcgcactt gaagatgctg acttcgcgat gttgatgtgt 16080cccagcggcg aggaggatgt ccaagcgcaa atacaaggaa gagatgctcc aggtcatcgc 16140gcctgagatc tacggccccg cggcggcggt gaaggaggaa agaaagcccc gcaaactgaa 16200gcgggtcaaa aaggacaaaa aggaggagga agatgacgga ctggtggagt ttgtgcgcga 16260gttcgccccc cggcggcgcg tgcagtggcg cgggcggaaa gtgaaaccgg tgctgcggcc 16320cggcaccacg gtggtcttca cgcccggcga gcgttccggc tccgcctcca agcgctccta 16380cgacgaggtg tacggggacg aggacatcct cgagcaggcg gtcgagcgtc tgggcgagtt 16440tgcgtacggc aagcgcagcc gccccgcgcc cttgaaagag gaggcggtgt ccatcccgct 16500ggaccacggc aaccccacgc cgagcctgaa gccggtgacc ctgcagcagg tgctaccgag 16560cgcggcgccg cgccggggct tcaagcgcga gggcggcgag gatctgtacc cgaccatgca 16620gctgatggtg cccaagcgcc agaagctgga ggacgtgctg gagcacatga aggtggaccc 16680cgaggtgcag cccgaggtca aggtgcggcc catcaagcag gtggccccgg gcctgggcgt 16740gcagaccgtg gacatcaaga tccccacgga gcccatggaa acgcagaccg agcccgtgaa 16800gcccagcacc agcaccatgg aggtgcagac ggatccctgg atgccagcac cagcttccac 16860cagcactcgc cgaagacgca agtacggcgc ggccagcctg ctgatgccca actacgcggc 16920tgcatccttc catcatcccc acgccgggct accgcggcac gcgcttctac cgcggctaca 16980ccagcagccg ccgccgcaag accaccaccc gccgccgtcg tcgcagccgc cgcagcagca 17040ccgcgacttc cgccttggtg cggagagtgt atcgcagcgg gcgcgagcct ctgaccctgc 17100cgcgcgcgcg ctaccacccg agcatcgcca tttaactacc gcctcctact tgcagatatg 17160gccctcacat gccgcctccg cgtccccatt acgggctacc gaggaagaaa gccgcgccgt 17220agaaggctga cggggaacgg gctgcgtcgc catcaccacc ggcggcggcg cgccatcagc 17280aagcggttgg ggggaggctt cctgcccgcg ctgatcccca tcatcgccgc ggcgatcggg 17340gcgatccccg gcatagcttc cgtggcggtg caggcctctc agcgccactg agacacaaaa 17400aagcatggat ttgtaataaa aaaaaaaatg gactgacgct cctggtcctg tgatgtgtgt 17460ttttagatgg aagacatcaa tttttcgtcc ctggcaccgc gacacggcac gcggccgttt 17520atgggcacct ggagcgacat cggcaacagc caactgaacg ggggcgcctt caattggagc 17580agtctctgga gcgggcttaa gaatttcggg tccacgctca aaacctatgg caacaaggcg 17640tggaacagca gcacagggca ggcgctgagg gaaaagctga aagaacagaa cttccagcag 17700aaggtggttg atggcctggc ctcaggcatc aacggggtgg ttgacctggc caaccaggcc 17760gtgcagaaac agatcaacag ccgcctggac gcggtcccgc ccgcggggtc cgtggagatg 17820
ccccaggtgg aggaggagct gcctcccctg gacaagcgcg gcgacaagcg accgcgtccc 17880gacgcggagg agacgctgct gacgcacacg gacgagccgc ccccgtacga ggaggcggtg 17940aaactgggcc tgcccaccac gcggcccgtg gcgcctctgg ccaccggagt gctgaaaccc 18000agcagcagcc agcccgcgac cctggacttg cctccgcctc gcccctccac agtggctaag 18060cccctgccgc cggtggccgt cgcgtcgcgc gccccccgag gccgccccca ggcgaactgg 18120cagagcactc tgaacagcat cgtgggtctg ggagtgcaga gtgtgaagcg ccgccgctgc 18180tattaaaaga cactgtagcg cttaacttgc ttgtctgtgt gtatatgtat gtccgccgac 18240cagaaggagg agtgtgaaga ggcgcgtcgc cgagttgcaa gatggccacc ccatcgatgc 18300tgccccagtg ggcgtacatg cacatcgccg gacaggacgc ttcggagtac ctgagtccgg 18360gtctggtgca gttcgcccgc gccacagaca cctacttcag tctggggaac aagtttagga 18420accccacggt ggcgcccacg cacaatgtga ccaccgaccg cagccagcgg ctgacggtgc 18480gcttcgtgcc cgtggaccgc gaggacaaca cctactcgta caaagtgcgc tacacgctgg 18540ccgtgggcga caaccgcgtg ctggacatgg ccagcaccta ctttgacatc cgcggcgtgc 18600tggaccgggg ccctagcttc aaaccctact ctggcaccgc ctacaacagc ctagctccca 18660agggagctcc caattccagc cagtgggagc aagcaaaaac aggcaatggg ggaactatgg 18720aaacacacac atatggtgtg gccccaatgg gcggagagaa tattacaaaa gatggtcttc 18780aaattggaac tgacgttaca gcgaatcaga ataaaccaat ttatgccgac aaaacatttc 18840aaccagaacc gcaagtagga gaagaaaatt ggcaagaaac tgaaaacttt tatggcggta 18900gagctcttaa aaaagacaca aacatgaaac cttgctatgg ctcctatgct agacccacca 18960atgaaaaagg aggtcaagct aaacttaaag ttggagatga tggagttcca accaaagaat 19020tcgacataga cctggctttc tttgatactc ccggtggcac cgtgaacggt caagacgagt 19080ataaagcaga cattgtcatg tataccgaaa acacgtattt ggaaactcca gacacgcatg 19140tggtatacaa accaggcaag gatgatgcaa gttctgaaat taacctggtt cagcagtcta 19200tgcccaacag acccaactac attgggttca gggacaactt tatcggtctt atgtactaca 19260acagcactgg caatatgggt gtgcttgctg gtcaggcctc ccagctgaat gctgtggttg 19320atttgcaaga cagaaacacc gagctgtcct accagctctt gcttgactct ttgggtgaca 19380gaacccggta tttcagtatg tggaaccagg cggtggacag ttatgacccc gatgtgcgca 19440tcatcgaaaa ccatggtgtg gaggatgaat tgccaaacta ttgcttcccc ttggacggct 19500ctggcactaa cgccgcatac caaggtgtga aagtaaaaga tggtcaagat ggtgatgttg 19560agagtgaatg ggaaaatgac gatactgttg cagctcgaaa tcaattatgt aaaggtaaca 19620ttttcgccat ggagattaat ctccaggcta acctgtggag aagtttcctc tactcgaacg 19680tggccctgta cctgcccgac tcctacaagt acacgccgac caacgtcacg ctgccgacca 19740acaccaacac ctacgattac atgaatggca gagtgacacc tccctcgctg gtagacgcct 19800acctcaacat cggggcgcgc tggtcgctgg accccatgga caacgtcaac cccttcaacc 19860accaccgcaa cgcgggcctg cgctaccgct ccatgctcct gggcaacggg cgctacgtgc 19920
ccttccacat ccaggtgccc caaaagtttt tcgccatcaa gagcctcctg ctcctgcccg 19980ggtcctacac ctacgagtgg aacttccgca aggacgtcaa catgatcctg cagagctccc 20040taggcaacga cctgcgcacg gacggggcct ccatcgcctt caccagcatc aacctctacg 20100ccaccttctt ccccatggcg cacaacaccg cctccacgct cgaggccatg ctgcgcaacg 20160acaccaacga ccagtccttc aacgactacc tctcggcggc caacatgctc taccccatcc 20220cggccaacgc caccaacgtg cccatctcca tcccctcgcg caactgggcc gccttccgcg 20280gatggtcctt cacgcgcctg aagacccgcg agacgccctc gctcggctcc gggttcgacc 20340cctacttcgt ctactcgggc tccatcccct acctagacgg caccttctac ctcaaccaca 20400ccttcaagaa ggtctccatc accttcgact cctccgtcag ctggcccggc aacgaccgcc 20460tcctgacgcc caacgagttc gaaatcaagc gcaccgtcga cggagaggga tacaacgtgg 20520cccagtgcaa catgaccaag gactggttcc tggtccagat gctggcccac tacaacatcg 20580gctaccaggg cttctacgtg cccgagggct acaaggaccg catgtactcc ttcttccgca 20640acttccagcc catgagccgc caggtcgtgg acgaggtcaa ctacaaggac taccaggccg 20700tcaccctggc ctaccagcac aacaactcgg gcttcgtcgg ctacctcgcg cccaccatgc 20760gccagggcca gccctacccc gccaactacc cctacccgct catcggcaag agcgccgtcg 20820ccagcgtcac ccagaaaaag ttcctctgcg accgggtcat gtggcgcatc cccttctcca 20880gcttcctcaa tgcccactcc gcctactttc gctcccaccg cgcgcgcatc gagaaggcca 20940gcaacttcat gtccatgggc gcgctcaccg acctcggcca gaacatgctc tacgccaact 21000ccgcccacgc gctagacatg aatttcgaag tcgaccccat ggatgagtcc acccttctct 21060atgttgtctt cgaagtcttc gacgtcgtcc gagtgcacca gccccaccgc ggcgtcatcg 21120aagccgtcta cctgcgcacg cccttctcgg ccggcaacgc caccacctaa gccgctcttg 21180cttcttgcaa gatgacggcg ggctccggcg agcaggagct cagggccatc ctccgcgacc 21240tgggctgcgg gccctgcttc ctgggcacct tcgacaagcg cttccctgga ttcatggccc 21300cgcacaagct ggcctgcgcc atcgtgaaca cggccggccg cgagaccggg ggcgagcact 21360ggctggcctt cgcctggaac ccgcgctccc acacatgcta cctcttcgac cccttcgggt 21420tctcggacga gcgcctcaag cagatctacc agttcgagta cgagggcctg ctgcgtcgca 21480gcgccctggc caccgaggac cgctgcgtca ccctggaaaa gtccacccag accgtgcagg 21540gtccgcgctc ggccgcctgc gggctcttct gctgcatgtt cctgcacgcc ttcgtgcact 21600ggcccgaccg ccccatggac aagaacccca ccatgaactt actgacgggg gtgcccaacg 21660gcatgctcca gtcgccccag gtggaaccca ccctgcgccg caaccaggaa gcgctctacc 21720ccgccttcga ccgcatgaat caagacatgt aaaaaaccgg tgtgtgtatg tgaatgcttt 21780attcataata aacagcacat gtttatgcca ccttctctga ggctctgact ttatttagaa 21840atcgaagggg ttctgccggc tctcggcatg gcccgcgggc agggatacgt tgcggaactg 21900gtacttgggc agccacttga actcggggat cagcagcttg ggcacgggga ggtcggggaa 21960cgagtcgctc cacagcttgc gcgtgagttg cagggcgccc agcaggtcgg gcgcggagat 22020
cttgaaatcg cagttgggac ccgcgttctg cgcgcgagag ttgcggtaca cggggttgca 22080gcactggaac accatcaggg ccgggtgctt cacgcttgcc agcaccgtcg cgtcggtgat 22140gccctccacg tccagatcct cggcgttggc catcccgaag ggggtcatct tgcaggtctg 22200ccgccccatg ctgggcacgc agccgggctt gtggttgcaa tcgcagtgca gggggatcag 22260catcatctgg gcctgctcgg agctcatgcc cgggtacatg gccttcatga aagccttcag 22320ctggcggaag gcctgctgcg ccttgccgcc ctcggtgaag aagaccccgc aggacttgct 22380agagaactgg ttggtggcgc agccggcgtc gtgcacgcag cagcgcgcgt cgttgttggc 22440cagctgcacc acgctgcgcc cccagcggtt ctgggtgatc ttggcccggt tggggttctc 22500cttcagcgcg cgctgcccgt tctcgctcgc cacatccatc tcgatagtgt gctccttctg 22560gatcatcacg gtcccgtgca ggcaccgcag cttgccctcg gcttcggtgc agccgtgcag 22620ccacagcgcg cagccggtgc actcccagtt cttgtgggcg atctgggagt gcgagtgcac 22680gaagccctgc aggaagcggc ccatcatcgc ggtcagggtc ttgttgctgg tgaaggtcag 22740cgggatgccg cggtgctcct cgttcacata caggtggcag atgcggcggt acacctcgcc 22800ctgctcgggc atcagctgga aggcggactt caggtcgctc tccacgcggt accggtccat 22860cagcagcgtc atcacttcca tgcccttctc ccaggccgaa acgatcggca ggctcagggg 22920gttcttcacc gccattgtca tcttagtcgc cgccgccgag gtcagggggt cgttctcgtc 22980cagggtctca aacactcgct tgccgtcctt ctcgatgatg cgcacggggg gaaagctgaa 23040gcccacggcc gccagctcct cctcggcctg cctttcgtcc tcgctgtcct ggctgatgtc 23100ttgcaaaggc acatgcttgg tcttgcgggg tttctttttg ggcggcagag gcggcggcga 23160tgtgctggga gagcgcgagt tctcgttcac cacgactatt tcttcttctt ggccgtcgtc 23220cgagaccacg cggcggtagg catgcctctt ctggggcaga ggcggaggcg acgggctctc 23280gcggttcggc gggcggctgg cagagcccct tccgcgttcg ggggtgcgct cctggcggcg 23340ctgctctgac tgacttcctc cgcggccggc cattgtgttc tcctagggag caacaacaag 23400catggagact cagccatcgt cgccaacatc gccatctgcc cccgccgcca ccgccgacga 23460gaaccagcag cagaatgaaa gcttaaccgc cccgccgccc agccccacct ccgacgccgc 23520ggccccagac atgcaagaga tggaggaatc catcgagatt gacctgggct acgtgacgcc 23580cgcggagcac gaggaggagc tggcagcgcg cttttcagcc ccggaagaga accaccaaga 23640gcagccagag caggaagcag agaacgagca gaaccaggct gggcacgagc atggcgacta 23700cctgagcggg gcagaggacg tgctcatcaa gcatctggcc cgccaatgca tcatcgtcaa 23760ggacgcgctg ctcgaccgcg ccgaggtgcc cctcagcgtg gcggagctca gccgcgccta 23820cgagcgcaac ctcttctcgc cgcgcgtgcc ccccaagcgc cagcccaacg gcacctgtga 23880gcccaacccg cgcctcaact tctacccggt cttcgcggtg cccgaggccc tggccaccta 23940ccacctcttt ttcaagaacc aaaggatccc cgtctcctgc cgcgccaacc gcacccgcgc 24000cgacgccctg ctcaacctgg gccccggcgc ccgcctacct gatatcacct ccttggaaga 24060ggttcccaag atcttcgagg gtctgggcag cgacgagact cgggccgcga acgctctgca 24120
aggaagcgga gaggagcatg agcaccacag cgccctggtg gagttggaag gcgacaacgc 24180gcgcctggcg gtcctcaagc gcacggtcga gctgacccac ttcgcctacc cggcgctcaa 24240cctgcccccc aaggtcatga gcgccgtcat ggaccaggtg ctcatcaagc gcgcctcgcc 24300cctctcggag gaggagatgc aggaccccga gagttcggac gagggcaagc ccgtggtcag 24360cgacgagcag ctggcgcgct ggctgggagc gagtancacc ccccagagcc tggaagagcg 24420gcgcaagctc atgatggccg tggtcctggt gaccgtggag ctggagtgtc tgcgccgctt 24480ctttgccgac gcggagaccc tgcgcaaggt cgaggagaac ctgcactacc tcttcaggca 24540cgggttcgtg cgccaggcct gcaagatctc caacgtggag ctgaccaacc tggtctccta 24600catgggcatc ctgcacgaga accgcctggg gcaaaacgtg ctgcacacca ccctgcgcgg 24660ggaggcccgc cgcgactaca tccgcgactg cgtctacctg tacctctgcc acacctggca 24720gacgggcatg ggcgtgtggc agcagtgcct ggaggagcag aacctgaaag agctctgcaa 24780gctcctgcag aagaacctca aggccctgtg gaccgggttc gacgagcgta ccaccgcctc 24840ggacctggcc gacctcatct tccccgagcg cctgcggctg acgctgcgca acgggctgcc 24900cgactttatg agccaaagca tgttgcaaaa ctttcgctct ttcatcctcg aacgctccgg 24960gatcctgccc gccacctgct ccgcgctgcc ctcggacttc gtgccgctga ccttccgcga 25020gtgccccccg ccgctctgga gccactgcta cttgctgcgc ctggccaact acctggccta 25080ccactcggac gtgatcgagg acgtcagcgg cgagggtctg ctggagtgcc actgccgctg 25140caacctctgc acgccgcacc gctccctggc ctgcaacccc cagctgctga gcgagaccca 25200gatcatcggc accttcgagt tgcaaggccc cggcgacggc gagggcaagg ggggtctgaa 25260actcaccccg gggctgtgga cctcggccta cttgcgcaag ttcgtgcccg aggactacca 25320tcccttcgag atcaggttct acgaggacca atcccagccg cccaaggccg agctgtcggc 25380ctgcgtcatc acccaggggg ccatcctggc ccaattgcaa gccatccaga aatcccgcca 25440agaatttctg ctgaaaaagg gccacggggt ctacttggac ccccagaccg gagaggagct 25500caaccccagc ttcccccagg atgccccgag gaagcagcaa gaagctgaaa gtggagctgc 25560cgccgccgga ggatttggag gaagactggg agagcagtca ggcagaggag gaggagatgg 25620aagactggga cagcactcag gcagaggagg acagcctgca agacagtctg gaggaggaag 25680acgaggtgga ggaggcagag gaagaagcag ccgccgccag accgtcgtcc tcggcggaga 25740aagcaagcag cacggatacc atctccgctc cgggtcgggg tcgcggcggc cgggcccaca 25800gtaggtggga cgagaccggg cgcttccgaa ccccaccacc cagaccggta agaaggagcg 25860gcagggatac aagtcctggc gggggcacaa aaacgccatc gtctcctgct tgcaagcctg 25920cgggggcaac atctccttca cccggcgcta cctgctcttt caccgcgggg tgaacttccc 25980ccgcaacatc ttgcattact accgtcacct ccacagcccc tactactgtt tccaagaaga 26040ggcagaaacc cagcagcagc agaaaaccag cggcagcagc agctagaaaa tccacagcgg 26100cggcaggtgg actgaggatc gcggcgaacg agccggcgca gacccgggag ctgaggaacc 26160ggatctttcc caccctctat gccatcttcc agcagagtcg ggggcaggag caggaactga 26220
aagtcaagaa ccgttctctg cgctcgctca cccgcagttg tctgtatcac aagagcgaag 26280accaacttca gcgcactctc gaggacgccg aggctctctt caacaagtac tgcgcgctca 26340ctcttaaaga gtagcccgcg cccgcccaca cacggaaaaa ggcgggaatt acgtcaccac 26400ctgcgccctt cgcccgacca tcatgagcaa agagattccc acgccttaca tgtggagcta 26460ccagccccag atgggcctgg ccgccggcgc cgcccaggac tactccaccc gcatgaactg 26520gctcagtgcc gggcccgcga tgatctcacg ggtgaatgac atccgcgccc accgaaacca 26580gatactccta gaacagtcag cgatcaccgc cacgccccgc catcacctta atccgcgtaa 26640ttggcccgcc gccctggtgt accaggaaat tccccagccc acgaccgtac tacttccgcg 26700agacgcccag gccgaagtcc agctgactaa ctcaggtgtc cagctggccg gcggcgccgc 26760cctgtgtcgt caccgccccg ctcagggtat aaagcggctg gtgatccgag gcagaggcac 26820acagctcaac gacgaggtgg tgagctcttc gctgggtctg cgacctgacg gagtcttcca 26880actcgccgga tcggggagat cttccttcac gcctcgtcag gccgtcctga ctttggagag 26940ttcgtcctcg cagccccgct cgggcggcat cggcactctc cagttcgtgg aggagttcac 27000tccctcggtn tacttcaacc ccttctccgg ctcccccggc cactacccgg acgagttcat 27060cccgaacttc gacgccatca gcgagtcggt ggacggctac gattgaatgt cccatggtgg 27120cgcagctgac ctagctcggc ttcgacacct ggaccactgc cgccgcttcc gctgcttcgc 27180tcgggatctc gccgagtttg cctactttga gctgcccgag gagcaccctc agggcccagc 27240ccacggagtg cggatcatcg tcgaaggggg cctcgactcc cacctgcttc ggatcttcag 27300ccagcgaccg atcctggtcg agcgcgaaca aggacagacc cttcttactt tgtactgcat 27360ctgcaaccac cccggcctgc atgaaagtct ttgttgtctg ctgtgtactg agtataataa 27420aagctgagat cagcgactac tccggactcg attgtggtgt tcctgctatc aaccggtccc 27480tgttcttcac cgggaacgag accgagctcc agctccagtg taagccccac aagaagtacc 27540tcacctggct gttccagggc tccccgatcg ccgttgtcaa ccactgcgac aacgacggag 27600tcctgctgag cggccctgcc aaccttactt tttccacccg cagaagcaag ctccagctct 27660tccaaccctt cctccccggg acctatcagt gcgtctcagg accctgccat cacaccttcc 27720acctgatccc gaataccaca gcgccgctcc ccgctactaa caaccaaact acccaccaac 27780gccaccgtcg cgacctttcc tctgaatcta ataccactac cggaggtgag ctccgaggtc 27840gaccaacctc tgggatttac tacggcccct gggaggtggt ggggttaata gcgctaggcc 27900tagttgcggg tgggcttttg gttctctgct acctatacct cccttgctgt tcgtacttag 27960tggtgctgtg ttgctggttt aagaaatggg gaagatcacc ctagtgagct gcggtgcgct 28020ggtggcggtg ttgctttcga ttgtgggact gggcggcgcg gctgtagtga aggagaaggc 28080cgatccctgc ttgcatttca atcccaacaa atgccagctg agttttcagc ccgatggcaa 28140tcggtgcgcg gtactgatca agtgcggatg ggaatgcgag aacgtgagaa tcgagtacaa 28200taacaagact cggaacaata ctctcgcgtc cgtgtggcag cccggggacc ccgagtggta 28260caccgtctct gtccccggtg ctgacggctc cccgcgcacc gtgaataata ctttcatttt 28320
tgcgcacatg tgcaacacgg tcatgtggat gagcaagcag tacgatatgt ggccccccac 28380gaaggagaac atcgtggtct tctccatcgc ttacagcctg tgcacggcgc taatcaccgc 28440tatcgtgtgc ctgagcattc acatgctcat cgctattcgc cccagaaata atgccgagaa 28500agagaaacag ccataacacg ttttttcaca caccttgttt ttacagacaa tgcgtctgtt 28560aaatttttta aacattgtgc tcagtattgc ttatgcctct ggttatgcaa acatacagaa 28620aaccctttat gtaggatctg atggtacact agagngtacc caatcacaag ccaaggttgc 28680atggtatttt tatagaacca acactgatcc agttaaactt tgtaagggtg aattgccgcg 28740tacacataaa actccactta catttagttg cagcaataat aatcttacac ttttttcaat 28800tacaaaacaa tatactggta cttattacag tacaaacttt catacaggac aagataaata 28860ttatactgtt aaggtagaaa atcctaccac tcctagaact accaccacca ccactactgc 28920aaagcccact gtgaaaacta caactaggac caccacaact acagaaacca ccaccagcac 28980aacacttgct gcaactacac acacacacac taagctaacc ttacagacca ctaatgattt 29040gatcgccctg ctgcaaaagg gggataacag caccacttcc aatgaggaga tacccaaatc 29100catgattggc attattgttg ctgtagtggt gtgcatgttg atcatcgcct tgtgcatggt 29160gtactatgcc ttctgctaca gaaagcacag actgaacgac aagctggaac acttactaag 29220tgttgaattt taatttttta gaaccatgaa gatcctaggc ctttttagtt tttctatcat 29280tacctctgct ctttgtgaat cagtggatag agatgttact attaccactg gttctaatta 29340tacactgaaa gggccaccct caggtatgct ttcgtggtat tgctattttg gaactgacac 29400tgatcaaact gaattatgca attttcaaaa aggcaaaacc tcaaactcta aaatctctaa 29460ttatcaatgc aatggcactg atctgatact actcaatgtc acgaaagcat atggtggcag 29520ttattattgc cctggacaaa acactgaaga aatgattttt tacaaagtgg aagtggttga 29580tcccactaca ccacccacca ccacaactat tcataccaca cacacagaac aaacaccaga 29640ggcaacagaa gcagagttgg ccttccaggt tcacggagat tcctttgctg tcaatacccc 29700tacacccgat cagcggtgtc cggggccgct agtcagcggc attgtcggtg tgctttcggg 29760attagcagtc ataatcatct gcatgttcat ttttgcttgc tgctatagaa ggctttaccg 29820acaaaaatca gacccactgc tgaacctcta tgtttaattt tttccagagc catgaaggca 29880gttagcgctc tagttttttg ttctttgatt ggcattgttt ttaatagtaa aattaccaga 29940gttagcttta ttaaacatgt taatgtaact gaaggagata acatcacact agcaggtgta 30000gaaggtgctc aaaacaccac ctggacaaaa taccatctag gatggagaga tatttgcacc 30060tggaatgtaa cttattattg cataggagtt aatcttacca ttgttaacgc taaccaatct 30120cagaatgggt taattaaagg acagagtgtt agtgtgacca gtgatgggta ctatacccag 30180catagtttta actacaacat tactgtcata ccactgccta cgcctagccc acctagcact 30240accacacaga caaccacata cagtacatca aatcagccta ccaccactac agcagcagag 30300gttgccagct cgtctggggt ccgagtggca tttttgatgt tggccccatc tagcagtccc 30360actgctagta ccaatgagca gactactgaa tttttgtcca ctgtcgagag ccacaccaca 30420
gctacctcca gtgccttctc tagcaccgcc aatctctcct cgctttcctc tacaccaatc 30480agccccgcta ctactcctag ccccgctcct cttcccactc ccctgaagca aacagacggc 30540ggcatgcaat ggcagatcac cctgctcatt gtgatcgggt tggtcatcct ggccgtgttg 30600ctctactaca tcttctgccg ccgcattccc aacgcgcacc gcaagccggc ctacaagccc 30660atcgttatcg ggcagccgga gccgcttcag gtggaagggg gtctaaggaa tcttctcttc 30720tcttttacag tatggtgatt gaantatgat tcctagacaa ttcttgatca ctattcttat 30780ctgcctcctc caagtctgtg ccaccctcgc tctggtggcc aacgccagtc cagactgtat 30840tgggcccttc gcctcctacg tgctctttgc cttcgtcacc tgcatctgct gctgtagcat 30900agtctgcctg cttatcacct tcttccagtt cattgactgg atctttgtgc gcatcgccta 30960cctgcgccac cacccccagt accgcgacca gcgagtggcg cagctgctca ggctcctctg 31020ataagcatgc gggctctgct acttntcgcg cttctgctgt tagtgctccc ccgtcccgtc 31080gacccccggt cccccactca gtcccccgag gaggttcgca aatgcaaatt ccaagaaccc 31140tggaaattcc tcaaatgcta ccgccaaaaa tcagacatgc atcccagctg gatcatgatc 31200attgggatcg tgaacattct ggcctgcacc ctcatctcct ttgtgattta cccctgcttt 31260gactttggtt ggaactcgcc agaggcgctc tatctcccgc ctgaacctga cacaccacca 31320cagcatcaac ctcaggcaca cgcactacca ccaccacagc ctaggccaca atacatgccc 31380atattagact atgaggccga gccacagcga cccatgctcc ccgctattag ttacttcaat 31440ctaaccggcg gagatgactg acccactggc caataacaac gtcaacgacc ttctcctgga 31500catggacggc cgcgcctcgg agcagcgact cgcccaactt cgcattcgtc agcagcagga 31560gagagccgtc aaggagctgc aggacggcat agccatccac cagtgcaaga gaggcatctt 31620ctgcctggtg aaacaggcca agatctccta cgaggtcacc cagaccgacc atcgcctctc 31680ctacgagctc ctgcagcagc gccagaagtt cacctgcctg gtcggagtca accccatcgt 31740catcacccag ccagcagtcg ggcgatacca aggggtgcat ccactgctcc tgcgactccc 31800ccgactgcgt ccacactctg atcaagaccc tctgcggcct ccgcgacctc ctccccatga 31860actaatcacc cccttatcca gtgaaataaa gatcatattg atgatgattt aaataaaaaa 31920aataatcatt tgatttgaaa taaagataca atcatattga tgatttgagt ttaacaaaaa 31980taaagaatca cttacttgaa atctgatacc aggtctctgt ccatgttttc tgccaacacc 32040acctcactcc cctcttccca gctctggtac tgcaggcccc ggcgggctgc aaacttcctc 32100cacacgctga aggggatgtc aaattcctcc tgtccctcaa tcttcatttt atcttctatc 32160agatgtccaa aaagcgcgtc cgggtggatg atgacttcga ccccgtctac ccctacgatg 32220cagacaacgc accgaccgtg cccttcatca accccccctt cgtctcttca gatggattcc 32280aagagaagcc cctgggggtg ttgtccctgc gactggctga ccccgtcacc accaagaacg 32340gggaaatcac cctcaagctg ggagaggggg tggacctcga ctcgtcggga aaactcatct 32400ccaacacggc caccaaggcc gccgcccctc tcagtatttc aaacaacacc atttccctta 32460aaactgctgc ccctttctac aacaacaatg gaactttaag cctcaatgtc tccacaccat 32520
tagcagtatt tcccacattt aacactttag gcataagtct tggaaacggt cttcagactt 32580caaataagtt gttgactgta caactaactc atcctcttac attcagctca aatagcatca 32640cagtaaaaac agacaaaggg ctatatatta actccagtgg aaacagagga cttgaggcta 32700atataagcct aaaaagagga ctagtttttg acggtaatgc tattgcaaca tatattggaa 32760atggcttaga ctatggatct tatgatagtg atggaaaaac aagacccgta attaccaaaa 32820ttggagcagg attaaatttt gatgctaaca aagcaatagc tgtcaaacta ggcacaggtt 32880taagttttga ctccgctggt gccttgacag ctggaaacaa acaggatgac aagctaacac 32940tttggactac ccctgaccca agccctaatt gtcaattact ttcagacaga gatgccaaat 33000ttactctctg tcttacaaaa tgcggtagtc aaatactagg cactgtggca gtggcggctg 33060ttactgtagg atcagcacta aatccaatta atgacacagt caaaagcgcc atagttttcc 33120ttagatttga ttccgatggt gtactcatgt caaactcatc aatggtaggt gattactgga 33180actttaggga gggacagacc actcaaagtg tagcctatac aaatgctgtg ggattcatgc 33240caaatatagg tgcatatcca aaaacccaaa gtaaaacacc taaaaatagc atagtcagtc 33300aggtatattt aactggagaa actactatgc caatgacact aaccataact ttcaatggca 33360ctgatgaaaa agacacaacc ccagttagca cctactctat gacttttaca tggcagtgga 33420ctggagacta taaggacaaa aatattacct ttgctaccaa ctcattctct ttttcctaca 33480tcgcccagga ataatcccac ccagcaagcc aacccctttt cccaccacct ttgtctatat 33540ggaaactctg aaacagaaaa ataaagttca agtgttttat tgaatcaaca gttttacagg 33600actcgagcag ttatttttcc tccaccctcc caggacatgg aatacaccac cctctccccc 33660cgcacagcct tgaacatctg aatgccattg gtgatggaca tgcttttggt ctccacgttc 33720cacacagttt cagagcgagc cagtctcgga tcggtcaggg agatgaaacc ctccgggcac 33780tcccgcatct gcacctcaca gctcaacagc tgaggattgt cctcggtggt cgggatcacg 33840gttatctgga agaagcagaa gagcggcggt gggaatcata gtccgcgaac gggatcggcc 33900ggtggtgtcg catcaggccc cgcagcagtc gctgccgccg ccgctccgtc aagctgctgc 33960tcagggggtt cgggtccagg gactccctca gcatgatgcc cacggccctc agcatcagtc 34020gtctggtgcg gcgggcgcag cagcgcatgc gaatctcgct caggtcactg cagtacgtgc 34080aacacaggac caccaggttg ttcaacagtc catagttcaa cacgctccag ccgaaactca 34140tcgcgggaag gatgctaccc acgtggccgt cgtaccagat cctcaggtaa atcaagtggc 34200gctccctcca gaagacgctg cccatgtaca tgatctcctt gggcatgtgg cggttcacca 34260cctcccggta ccacatcacc ctctggttga acatgcagcc ccggatgatc ctgcggaacc 34320acagggccag caccgccccg cccgccatgc agcgaagaga ccccggatcc cggcaatgac 34380aatggaggac ccaccgctcg tacccgtgga tcatctggga gctgaacaag tctatgttgg 34440cacagcacag gcatatgctc atgcatctct tcagcactct cagctcctcg ggggtcaaaa 34500ccatatccca gggcacgggg aactcttgca ggacagcgaa ccccgcagaa cagggcaatc 34560ctcgcacata acttacattg tgcatggaca gggtatcgca atcaggcagc accgggtgat 34620
cctccaccag agaagcgcgg gtctcggtct cctcacagcg tggtaagggg gccggccgat 34680acgggtgatg gcgggacgcg gctgatcgtg ttctcgaccg tgtcatgatg cagttgcttt 34740cggacatttt cgtacttgct gtagcagaac ctggtccggg cgctgcacac cgatcgccgg 34800cggcggtctc ggcgcttgga acgctcggtg ttaaagttgt aaaacagcca ctctctcaga 34860ccgtgcagca gatctagggc ctcaggagtg atgaagatcc catcatgcct gatagctctg 34920atcacatcga ccaccgtgga atgggccagg cccagccaga tgatgcaatt ttgttgggtt 34980tcggtgacgg cgggggaggg aagaacagga agaaccatga ttaactttta atccaaacgg 35040tctcggagca cttcaaaatg aaggtcacgg agatggcacc tctcgccccc gctgtgttgg 35100tggaaaataa cagccaggtc aaaggtgata cggttctcga gatgttccac ggtggcttcc 35160agcaaagcct ccacgcgcac atcagaaaca agacaatagc gaaagcggga gggttctcta 35220attcctcaac catcatgtta cactcctgca ccatccccag ataattttca tttttccagc 35280cttgaatgat tcgaactagt tcctgaggta aatccaagcc agccatgata aaaagctcgc 35340gcagagcacc ctccaccggc attcttaagc acaccctcat aattccaaga tattctgctc 35400ctggttcacc tgcagcagat tgacaagcgg aatatcaaaa tctctgccgc gatccctgag 35460ctcctccctc agcaataact gtaagtactc tttcatatcg tctccgaaat ttttagccat 35520aggaccccca ggaataagag aagggcaagc cacattacag ataaaccgaa gtccccccca 35580gtgagcattg ccaaatgtaa gattgaaata agcatgctgg ctagacccgg tgatatcttc 35640cagataactg gacagaaaat cgggtaagca atttttaaga aaatcaacaa aagaaaaatc 35700ttccaggtgc acgtttaggg cctcgggaac aacgatggag taagtgcaag gggtgcgttc 35760cagcatggtt agttagctga tctgtaaaaa aacaaaaaat aaaacattaa accatgctag 35820cctggcgaac aggtgggtaa atcgttctct ccagcaccag gcaggccacg gggtctccgg 35880cgcgaccctc gtaaaaattg tcgctatgat tgaaaaccat cacagagaga cgttcccggt 35940ggccggcgtg aatgattcga gaagaagcat acaccccccg gaacattgga gtccgtgagt 36000gaaaaaaagc ggccgaggaa gcaatgaggc actacaacgc tcactctcaa gtccagcaaa 36060gcgatgccat gcggatgaag cacaaaattt tcaggtgcgt aaaaaatgta attactcccc 36120tcctgcacag gcagcgaagc tcccgatccc tccagataca catacaaagc ctcagcgtcc 36180atagcttacc gagcggcagc agcagcggca cacaacaggc gcaagagtca gagaaaagac 36240tgagctctaa cctgtccgcc cgctctctgc tcaatatata gccccagatc tacactgacg 36300taaaggccaa agtctaaaaa tacccgccaa ataatcacac acgcccagca cacgcccaga 36360aaccggtgac acactcagaa aaatacgcgc acttcctcaa acggccaaac tgccgtcatt 36420tccgggttcc cacgctacgt catcaaaaca cgactttcaa attccgtcga ccgttaaaaa 36480catcacccgc cccgccccta acggtcgccg ctcccgcagc caatcacctt cctccctccc 36540caaattcaaa cagctcattt gcatattaac gcgcaccaaa agtttgaggt atattattga 36600tgatgg36606
210421136535212DNA213黑猩猩Pan 7(CV33)基因組4004catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agctgtttga 60atttggggag ggaggaaggt gattggccga gagacgggcg accgttaggg gcggggcggg 120tgacgttttg atgacgtggc cgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600gtaatgtttt cctggctact gggaacgaga ttctggaatt ggtggtggac gccatgatgg 660gtggcgaccc tcctgagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960aggaggcgat tcgagctgca tcgaaccagg gagtgaaagc tgcgggcgaa agctttagcc 1020tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140acagtaagtg tgattaactt tagttgggaa ggcagagggt gactgggtgc tgactggttt 1200atttatgtat atgttttttt atgtgtaggt cccgtctctg acgtagatga gacccccact 1260tcagagtgca tttcatcacc cccagaaatt ggcgaggaac cgcccgaaga tattattcat 1320agaccagttg cagtgagagt caccgggcgg agagcagctg tggagagttt ggatgacttg 1380ctacagggtg gggatgaacc tttggacttg tgtacccgga aacgccccag gcactaagtg 1440ccacacatgt gtgtttactt aaggtgatgt cagtatttat agggtgtgga gtgcaataaa 1500atccgtgttg actttaagtg cgtggtttat gactcagggg tggggactgt gggtatataa 1560gcaggtgcag acctgtgtgg tcagttcaga gcaggactca tggagatctg gacggtcttg 1620gaagactttc accagactag acagctgcta gagaactcat cggagggggt ctcttacctg 1680tggagattct gcttcggtgg gcctctagct aagctagtct atagggccaa acaggattat 1740
aaggatcaat ttgaggatat tttgagagag tgtcctggta tttttgactc tctcaacttg 1800ggccatcagt ctcactttaa ccagagtatt ctgagagccc ttgacttttc tactcctggc 1860agaactaccg ccgcggtagc cttttttgcc tttatccttg acaaatggag tcaagaaacc 1920catttcagca gggattaccg tctggactgc ttagcagtag ctttgtggag aacatggagg 1980tgccagcgcc tgaatgcaat ctccggctac ttgccagtac agccggtaga cacgctgagg 2040atcctgagtc tccagtcacc ccaggaacac caacgccgcc agcagccgca gcaggagcag 2100cagcaagagg aggaggagga tcgagaagag aacccgagag ccggtctgga ccctccggtg 2160gcggaggagg aggagtagct gacttgtttc ccgagctgcg ccgggtgctg actaggtctt 2220ccagtggacg ggagaggggg attaagcggg agaggcatga ggagactagc cacagaactg 2280aactgactgt cagtctgatg agccgcaggc gcccagaatc ggtgtggtgg catgaggttc 2340agtcgcaggg gatagatgag gtctcggtga tgcatgagaa atattccctg gaacaagtca 2400agacttgttg gttggagcct gaggatgatt gggaggtagc catcaggaat tatgccaagc 2460tggctctgaa gccagacaag aagtacaaga ttaccaaact gattaatatc agaaattcct 2520gctacatttc agggaatggg gccgaggtgg agatcagtac ccaggagagg gtggccttca 2580gatgttgtat gatgaatatg tacccggggg tggtgggcat ggagggagtc acctttatga 2640acgcgaggtt caggggtgat gggtataatg gggtggtctt tatggccaac accaagctga 2700cagtgcacgg atgctccttc tttgggttca ataacatgtg catcgaggcc tggggcagtg 2760tttcagtgag gggatgcagc ttttcagcca actggatggg ggtcgtgggc agaaccaaga 2820gcaaggtgtc agtgaagaaa tgcctgttcg agaggtgcca cctgggggtg atgagcgagg 2880gcgaagccaa agtcaaacac tgcgcctcta ctgagacggg ctgctttgtg ctgatcaagg 2940gcaatgccca agtcaagcat aacatgatct gtggggcctc ggatgagcgc ggctaccaga 3000tgctgacctg cgccggtggg aacagccata tgctggccac cgtgcatgtg acctcgcacc 3060cccgcaagac atggcccgag ttcgagcaca acgtcatgac ccgatgcaat gtgcacctgg 3120ggtcccgccg aggcatgttc atgccctacc agtgcaacat gcaatttgtg aaggtgctgc 3180tggagcccga tgccatgtcc agagtgagcc tgacgggggt gtttgacatg aatgtggagc 3240tgtggaaaat tctgagatat gatgaatcca agaccaggtg ccgggcctgc gaatgcggag 3300gcaagcacgc caggcttcag cccgtgtgtg tggaggtgac ggaggacctg cgacccgatc 3360atttggtgtt gtcctgcaac gggacggagt tcggctccag cggggaagaa tctgactaga 3420gtgagtagtg tttgggggag gtggagggct tgtatgaggg gcagaatgac taaaatctgt 3480gtttttctgt gtgttgcagc agcatgagcg gaagcgcctc ctttgaggga ggggtattca 3540gcccttatct gacggggcgt ctcccctcct gggcgggagt gcgtcagaat gtgatgggat 3600ccacggtgga cggccggccc gtgcagcccg cgaactcttc aaccctgacc tacgcgaccc 3660tgagctcctc gtccgtggac gcagctgccg ccgcagctgc tgcttccgcc gccagcgccg 3720tgcgcggaat ggccctgggc gccggctact acagctctct ggtggccaac tcgacttcca 3780ccaataatcc cgccagcctg aacgaggaga agctgctgct gctgatggcc cagctcgagg 3840
ccctgaccca gcgcctgggc gagctgaccc agcaggtggc tcagctgcag gcggagacgc 3900gggccgcggt tgccacggtg aaaaccaaat aaaaaatgaa tcaataaata aacggagacg 3960gttgttgatt ttaacacaga gtcttgaatc tttatttgat ttttcgcgcg cggtaggccc 4020tggaccaccg gtctcgatca ttgagcaccc ggtggatttt ttccaggacc cggtagaggt 4080gggcttggat gttgaggtac atgggcatga gcccgtcccg ggggtggagg tagctccatt 4140gcagggcctc gtgctcgggg gtggtgttgt aaatcaccca gtcatagcag gggcgcaggg 4200cgtggtgctg cacgatgtcc ttgaggagga gactgatggc cacgggcagc cccttggtgt 4260aggtgttgac gaacctgttg agctgggagg gatgcatgcg gggggagatg agatgcatct 4320tggcctggat cttgagattg gcgatgttcc cgcccagatc ccgccggggg ttcatgttgt 4380gcaggaccac cagcacggtg tatccggtgc acttggggaa tttgtcatgc aacttggaag 4440ggaaggcgtg aaagaatttg gagacgccct tgtgaccgcc caggttttcc atgcactcat 4500ccatgatgat ggcgatgggc ccgtgggcgg cggcctgggc aaagacgttt cgggggtcgg 4560acacatcgta gttgtggtcc tgggtgagct cgtcataggc cattttaatg aatttggggc 4620ggagggtgcc cgactggggg acgaaggtgc cctcgatccc gggggcgtag ttgccctcgc 4680agatctgcat ctcccaggcc ttgagctcgg agggggggat catgtccacc tgcggggcga 4740tgaaaaaaac ggtttccggg gcgggggaga tgagctgggc cgaaagcagg ttccggagca 4800gctgggactt gccgcagccg gtggggccgt agatgacccc gatgaccggc tgcaggtggt 4860agttgaggga gagacagctg ccgtcctcgc ggaggagggg ggccacctcg ttcatcatct 4920cgcgcacatg catgttctcg cgcacgagtt ccgccaggag gcgctcgccc cccagcgaga 4980ggagctcttg cagcgaggcg aagtttttca gcggcttgag cccgtcggcc atgggcattt 5040tggagagggt ctgttgcaag agttccagac ggtcccagag ctcggtgatg tgctctaggg 5100catctcgatc cagcagacct cctcgtttcg cgggttgggg cgactgcggg agtagggcac 5160caggcgatgg gcgtccagcg aggccagggt ccggtccttc cagggtcgca gggtccgcgt 5220cagcgtggtc tccgtcacgg tgaaggggtg cgcgccgggc tgggcgcttg cgagggtgcg 5280cttcaggctc atccggctgg tcgagaaccg ctcccggtcg gcgccctgcg cgtcggccag 5340gtagcaattg agcatgagtt cgtagttgag cgcctcggcc gcgtggccct tggcgcggag 5400cttacctttg gaagtgtgtc cgcagacggg acagaggagg gacttgaggg cgtagagctt 5460gggggcgagg aagacggact cgggggcgta ggcgtccgcg ccgcagctgg cgcagacggt 5520ctcgcactcc acgagccagg tgaggtcggg ccggttgggg tcaaaaacga ggtttcctcc 5580gtgctttttg atgcgtttct tacctctggt ctccatgagc tcgtgtcccc gctgggtgac 5640aaagaggctg tccgtgtccc cgtagaccga ctttatgggc cggtcctcga gcggggtgcc 5700gcggtcctcg tcgtagagga accccgccca ctccgagacg aaggcccggg tccaggccag 5760cacgaaggag gccacgtggg aggggtagcg gtcgttgtcc accagcgggt ccaccttctc 5820cagggtatgc aagcacatgt ccccctcgtc cacatccagg aaggtgattg gcttgtaagt 5880gtaggccacg tgaccggggg tcccggccgg gggggtataa aagggggcgg gcccctgctc 5940
gtcctcactg tcttccggat cgctgtccag gagcgccagc tgttggggta ggtattccct 6000ctcgaaggct ggcataacct cggcactcag gttgtcagtt tctagaaacg aggaggattt 6060gatattgacg gtgccgttgg agacgccttt catgagcccc tcgtccatct ggtcagaaaa 6120gacgatcttt ttgttgtcga gcttggtggc gaaggagccg tagagggcgt tggagaggag 6180cttggcgatg gagcgcatgg tctggttctt ttccttgtcg gcgcgctcct tggcggcgat 6240gttgagctgc acgtactcgc gcgccacgca cttccattcg gggaagacgg tggtgagctc 6300gtcgggcacg attctgaccc gccagccgcg gttgtgcagg gtgatgaggt ccacgctggt 6360ggccacctcg ccgcgcaggg gctcgttggt ccagcagagg cgcccgccct tgcgcgagca 6420gaaggggggc agcgggtcca gcatgagctc gtcggggggg tcggcgtcca cggtgaagat 6480gccgggcaga agctcggggt cgaagtagct gatgcaggtg tccagatcgt ccagcgccgc 6540ttgccagtcg cgcacggcca gcgcgcgctc gtaggggctg aggggcgtgc cccagggcat 6600ggggtgcgtg agcgcggagg cgtacatgcc gcagatgtcg tagacgtaga ggggctcctc 6660gaggacgccg atgtaggtgg ggtagcagcg ccccccgcgg atgctggcgc gcacgtagtc 6720gtacagctcg tgcgagggcg cgaggagccc cgtgccgagg ttggagcgtt gcggcttttc 6780ggcgcggtag acgatctggc ggaagatggc gtgggagttg gaggagatgg tgggcctctg 6840gaagatgttg aagtgggcgt ggggcaggcc gaccgagtcc ctgatgaagt gggcgtagga 6900gtcctgcagc ttggcgacga gctcggcggt gacgaggacg tccagggcgc agtagtcgag 6960ggtctcttgg atgatgtcgt acttgagctg gcccttctgc ttccacagct cgcggttgag 7020aaggaactct tcgcggtcct tccagtactc ttcgaggggg aacccgtcct gatcggcacg 7080gtaagagccc accatgtaga actggttgac ggccttgtag gcgcagcagc ccttctccac 7140ggggagggcg taagcttgtg cggccttgcg cagggaggtg tgggtgaggg cgaaggtgtc 7200gcgcaccatg accttgagga actggtgctt gaagtcgagg tcgtcgcagc cgccctgctc 7260ccagagctgg aagtccgtgc gcttcttgta ggcggggttg ggcaaagcga aagtaacatc 7320gttgaagagg atcttgcccg cgcggggcat gaagttgcga gtgatgcgga aaggctgggg 7380cacctcggcc cggttgttga tgacctgggc ggcgaggacg atctcgtcga agccgttgat 7440gttgtgcccg acgatgtaga gttccacgaa tcgcgggcgg cccttaacgt ggggcagctt 7500cttgagctcg tcgtaggtga gctcggcggg gtcgctgagc ccgtgctgct cgagggccca 7560gtcggcgacg tgggggttgg cgctgaggaa ggaagtccag agatccacgg ccagggcggt 7620ctgcaagcgg tcccggtact gacggaactg ctggcccacg gccatttttt cgggggtgac 7680gcagtagaag gtgcgggggt cgccgtgcca gcggtcccac ttgagctgga gggcgaggtc 7740gtgggcgagc tcgacgagcg gcgggtcccc ggagagtttc atgaccagca tgaaggggac 7800gagctgcttg ccgaaggacc ccatccaggt gtaggtttcc acatcgtagg tgaggaagag 7860cctttcggtg cgaggatgcg agccgatggg gaagaactgg atctcctgcc accagttgga 7920ggaatggctg ttgatgtgat ggaagtagaa atgccgacgg cgcgccgagc actcgtgctt 7980gtgtttatac aagcgtccgc agtgctcgca acgctgcacg ggatgcacgt gctgcacgag 8040
ctgtacctgg gttcctttga cgaggaattt cagtgggcag tggagcgctg gcggctgcat 8100ctggtgctgt actacgtcct ggccatcggc gtggccatcg tctgcctcga tggtggtcat 8160gctgacgagc ccgcgcggga ggcaggtcca gacttcggct cggacgggtc ggagagcgag 8220gacgagggcg cgcaggccgg agctgtccag ggtcctgaga cgctgcggag tcaggtcagt 8280gggcagcggc ggcgcgcggt tgacttgcag gagcttttcc agggcgcgcg ggaggtccag 8340atggtacttg atctccacgg cgccgttggt ggcgacgtcc acggcttgca gggtcccgtg 8400cccctggggc gccaccaccg tgccccgttt cttcttgggc gctgcttcca tgccggtcag 8460aagcggcggc gaggacgcgc gccgggcggc aggggcggct cgggacccgg aggcaggggc 8520ggcaggggca cgtcggcgcc gcgcgcgggc aggttctggt actgcgcccg gagaagactg 8580gcgtgagcga cgacgcgacg gttgacgtcc tggatctgac gcctctgggt gaaggccacg 8640ggacccgtga gtttgaacct gaaagagagt tcgacagaat caatctcggt atcgttgacg 8700gcggcctgcc gcaggatctc ttgcacgtcg cccgagttgt cctggtaggc gatctcggtc 8760atgaactgct cgatctcctc ctcctgaagg tctccgcggc cggcgcgctc gacggtggcc 8820gcgaggtcgt tggagatgcg gcccatgagc tgcgagaagg cgttcatgcc ggcctcgttc 8880cagacgcggc tgtagaccac ggctccgtcg gggtcgcgcg cgcgcatgac cacctgggcg 8940aggttgagct cgacgtggcg cgtgaagacc gcgtagttgc agaggcgctg gtagaggtag 9000ttgagcgtgg tggcgatgtg ctcggtgacg aagaagtaca tgatccagcg gcggagcggc 9060atctcgctga cgtcgcccag ggcttccaag cgctccatgg cctcgtagaa gtccacggcg 9120aagttgaaaa actgggagtt gcgcgccgag acggtcaact cctcctccag aagacggatg 9180agctcagcga tggtggcgcg cacctcgcgc tcgaaggccc cggggggctc ctcttcttcc 9240atctcttcct cctccactaa catctcttct acttcctcct caggaggcgg cggcggggga 9300ggggccctgc gtcgccggcg gcgcacgggc agacggtcga tgaagcgctc gatggtctcc 9360ccgcgccggc gacgcatggt ctcggtgacg gcgcgcccgt cctcgcgggg ccgcagcgtg 9420aagacgccgc cgcgcatctc caggtggccg ccgggggggt ctccgttggg cagggagagg 9480gcgctgacga tgcatcttat caattggccc gtagggactc cgcgcaagga cctgagcgtc 9540tcgagatcca cgggatccga aaaccgctga acgaaggctt cgagccagtc gcagtcgcaa 9600ggtaggctga gcccggtttc ttgttcttcg gggatttcgg gaggcgggcg ggcgatgctg 9660ctggtgatga agttgaagta ggcggtcctg agacggcgga tggtggcgag gagcaccagg 9720tccttgggcc cggcttgctg gatgcgcaga cggtcggcca tgccccaggc gtggtcctga 9780cacctggcga ggtccttgta gtagtcctgc atgagccgct ccacgggcac ctcctcctcg 9840cccgcgcggc cgtgcatgcg cgtgagcccg aacccgcgct ggggctggac gagcgccagg 9900tcggcgacga cgcgctcggc gaggatggcc tgctgtatct gggtgagggt ggtctggaag 9960tcgtcgaagt cgacgaagcg gtggtaggct ccggtgttga tggtatagga gcagttggcc 10020atgacggacc agttgacggt ctggtggccg ggtcgcacga gctcgtggta cttgaggcgc 10080gagtaggcgc gcgtgtcgaa gatgtagtcg ttgcaggtgc gcacgaggta ctggtatccg 10140
acgaggaagt gcggcggcgg ctggcggtag agcggccatc gctcggtggc gggggcgccg 10200ggcgcgaggt cctcgagcat gaggcggtgg tagccgtaga tgtacctgga catccaggtg 10260atgccggcgg cggtggtgga ggcgcgcggg aactcgcgga cgcggttcca gatgttgcgc 10320agcggcagga agtagttcat ggtggccgcg gtctggcccg tgaggcgcgc gcagtcgtgg 10380atgctctaga catacgggca aaaacgaaag cggtcagcgg ctcgactccg tggcctggag 10440gctaagcgaa cgggttgggc tgcgcgtgta ccccggttcg aatctcgaat caggctggag 10500ccgcagctaa cgtggtactg gcactcccgt ctcgacccaa gcctgctaac gaaacctcca 10560ggatacggag gcgggtcgtt ttttggcctt ggtcgctggt catgaaaaac tagtaagcgc 10620ggaaagcgac cgcccgcgat ggctcgctgc cgtagtctgg agaaagaatc gccagggttg 10680cgttgcggtg tgccccggtt cgagcctcag cgctcggcgc cggccggatt ccgcggctaa 10740cgtgggcgtg gctgccccgt cgtttccaag accccttagc cagccgactt ctccagttac 10800ggagcgagcc cctctttttc ttgtgttttt gccagatgca tcccgtactg cggcagatgc 10860gcccccaccc tccacctcaa ccgcccctac cgccgcagca gcagcaacag ccggcgcttc 10920tgcccccgcc ccagcagcag ccagccacta ccgcggcggc cgccgtgagc ggagccggcg 10980ttcagtatga cctggccttg gaagagggcg aggggctggc gcggctgggg gcgtcgtcgc 11040cggagcggca cccgcgcgtg cagatgaaaa gggacgctcg cgaggcctac gtgcccaagc 11100agaacctgtt cagagacagg agcggcgagg agcccgagga gatgcgcgcc tcccgcttcc 11160acgcggggcg ggagctgcgg cgcggcctgg accgaaagcg ggtgctgagg gacgaggatt 11220tcgaggcgga cgagctgacg gggatcagcc ccgcgcgcgc gcacgtggcc gcggccaacc 11280tggtcacggc gtacgagcag accgtgaagg aggagagcaa cttccaaaaa tccttcaaca 11340accacgtgcg cacgctgatc gcgcgcgagg aggtgaccct gggcctgatg cacctgtggg 11400acctgctgga ggccatcgtg cagaacccca cgagcaagcc gctgacggcg cagctgtttc 11460tggtggtgca gcacagtcgg gacaacgaga cgttcaggga ggcgctgctg aatatcaccg 11520agcccgaggg ccgctggctc ctggacctgg tgaacattct gcagagcatc gtggtgcagg 11580agcgcgggct gccgctgtcc gagaagctgg cggctatcaa cttctcggtg ctgagcctgg 11640gcaagtacta cgctaggaag atctacaaga ccccgtacgt gcccatagac aaggaggtga 11700agatcgacgg gttttacatg cgcatgaccc tgaaagtgct gaccctgagc gacgatctgg 11760gggtgtaccg caacgacagg atgcaccgcg cggtgagcgc cagccgccgg cgcgagctga 11820gcgaccagga gctgatgcac agcctgcagc gggccctgac cggggccggg accgaggggg 11880agagctactt tgacatgggc gcggacctgc gctggcagcc cagccgccgg gccttggaag 11940ctgccggcgg ttccccctac gtggaggagg tggacgatga ggaggaggag ggcgagtacc 12000tggaagactg atggcgcgac cgtatttttg ctagatgcag caacagccac cgcctcctga 12060tcccgcgatg cgggcggcgc tgcagagcca gccgtccggc attaactcct cggacgattg 12120gacccaggcc atgcaacgca tcatggcgct gacgacccgc aatcccgaag cctttagaca 12180gcagcctcag gccaaccggc tctcggccat cctggaggcc gtggtgccct cgcgctcgaa 12240
ccccacgcac gagaaggtgc tggccatcgt gaacgcgctg gtggagaaca aggccatccg 12300cggcgacgag gccgggctgg tgtacaacgc gctgctggag cgcgtggccc gctacaacag 12360caccaacgtg cagacgaacc tggaccgcat ggtgaccgac gtgcgcgagg cggtgtcgca 12420gcgcgagcgg ttccaccgcg agtcgaacct gggctccatg gtggcgctga acgccttcct 12480gagcacgcag cccgccaacg tgccccgggg ccaggaggac tacaccaact tcatcagcgc 12540gctgcggctg atggtggccg aggtgcccca gagcgaggtg taccagtcgg ggccggacta 12600cttcttccag accagtcgcc agggcttgca gaccgtgaac ctgagccagg ctttcaagaa 12660cttgcaggga ctgtggggcg tgcaggcccc ggtcggggac cgcgcgacgg tgtcgagcct 12720gctgacgccg aactcgcgcc tgctgctgct gctggtggcg cccttcacgg acagcggcag 12780cgtgagccgc gactcgtacc tgggctacct gcttaacctg taccgcgagg ccatcgggca 12840ggcgcacgtg gacgagcaga cctaccagga gatcacccac gtgagccgcg cgctgggcca 12900ggaggacccg ggcaacctgg aggccaccct gaacttcctg ctgaccaacc ggtcgcagaa 12960gatcccgccc cagtacgcgc tgagcaccga ggaggagcgc atcctgcgct acgtgcagca 13020gagcgtgggg ctgttcctga tgcaggaggg ggccacgccc agcgccgcgc tcgacatgac 13080cgcgcgcaac atggagccca gcatgtacgc tcgcaaccgc ccgttcatca ataagctgat 13140ggactacttg catcgggcgg ccgccatgaa ctcggactac tttaccaacg ccatcttgaa 13200cccgcactgg ctcccgccgc ccgggttcta cacgggcgag tacgacatgc ccgaccccaa 13260cgacgggttc ctgtgggacg acgtggacag cagcgtgttc tcgccgcgcc ccgccaccac 13320cgtgtggaag aaagagggcg gggaccggcg gccgtcctcg gcgctgtccg gtcgcgcggg 13380tgctgccgcg gcggtgcctg aggccgccag ccccttcccg agcctgccct tttcgctgaa 13440cagcgtgcgc agcagcgagc tgggtcggct gacgcggccg cgcctgctgg gcgaggagga 13500gtacctgaac gactccttgt tgaggcccga gcgcgagaag aacttcccca ataacgggat 13560agagagcctg gtggacaaga tgagccgctg gaagacgtac gcgcacgagc acagggacga 13620gccccgagct agcagcagcg caggcacccg tagacgccag cgacacgaca ggcagcgggg 13680tctggtgtgg gacgatgagg attccgccga cgacagcagc gtgttggact tgggtgggag 13740tggtggtggt aacccgttcg ctcacttgcg cccccgtatc gggcgcctga tgtaagaatc 13800tgaaaaaata aaaaacggta ctcaccaagg ccatggcgac cagcgtgcgt tcttctctgt 13860tgtttgtagt agtatgatga ggcgcgtgta cccggagggt cctcctccct cgtacgagag 13920cgtgatgcag caggcggtgg cggcggcgat gcagcccccg ctggaggcgc cttacgtgcc 13980cccgcggtac ctggcgccta cggaggggcg gaacagcatt cgttactcgg agctggcacc 14040cttgtacgat accacccggt tgtacctggt ggacaacaag tcggcggaca tcgcctcgct 14100gaactaccag aacgaccaca gcaacttcct gaccaccgtg gtgcagaaca acgatttcac 14160ccccacggag gccagcaccc agaccatcaa ctttgacgag cgctcgcggt ggggcggcca 14220gctgaaaacc atcatgcaca ccaacatgcc caacgtgaac gagttcatgt acagcaacaa 14280gttcaaggcg cgggtgatgg tctcgcgcaa gacccccaat ggggtcgcgg tggatgagaa 14340
ttatgatggt agtcaggacg agctgactta cgagtgggtg gagtttgagc tgcccgaggg 14400caacttctcg gtgaccatga ccatcgatct gatgaacaac gccatcatcg acaactactt 14460ggcggtgggg cgtcagaacg gggtgctgga gagcgacatc ggcgtgaagt tcgacacgcg 14520caacttccgg ctgggctggg accccgtgac cgagctggtg atgccgggcg tgtacaccaa 14580cgaggccttc caccccgaca tcgtcctgct gcccggctgc ggcgtggact tcaccgagag 14640ccgcctcagc aacctgctgg gcatccgcaa gcggcagccc ttccaggagg gcttccagat 14700cctgtacgag gacctggagg ggggcaacat ccccgcgctc ttggatgtcg aagcctatga 14760gaaaagcaag gaggaggccg ccgcagcggc gaccgcagcc gtggccaccg cctctaccga 14820ggtgcggggc gataattttg ctagcgccgc ggcagtggcc gaggcggctg aaaccgaaag 14880taagatagtc atccagccgg tggagaagga cagcaaggac aggagctaca acgtgctcgc 14940ggacaagaaa aacaccgcct accgcagctg gtacctggcc tacaactacg gcgaccccga 15000gaagggcgtg cgctcctgga cgctgctcac cacctcggac gtcacctgcg gcgtggagca 15060agtctactgg tcgctgcccg acatgatgca agacccggtc accttccgct ccacgcgtca 15120agttagcaac tacccggtgg tgggcgccga gctcctgccc gtctactcca agagcttctt 15180caacgagcag gccgtctact cgcagcagct gcgcgccttc acctcgctca cgcacgtctt 15240caaccgcttc cccgagaacc agatcctcgt ccgcccgccc gcgcccacca ttaccaccgt 15300cagtgaaaac gttcctgctc tcacagatca cgggaccctg ccgctgcgca gcagtatccg 15360gggagtccag cgcgtgaccg tcactgacgc cagacgccgc acctgcccct acgtctacaa 15420ggccctgggc gtagtcgcgc cgcgcgtcct ctcgagccgc accttctaaa aaatgtccat 15480tctcatctcg cccagtaata acaccggttg gggcctgcgc gcgcccagca agatgtacgg 15540aggcgctcgc caacgctcca cgcaacaccc cgtgcgcgtg cgcgggcact tccgcgctcc 15600ctggggcgcc ctcaagggcc gcgtgcgctc gcgcaccacc gtcgacgacg tgatcgacca 15660ggtggtggcc gacgcgcgca actacacgcc cgccgccgcg cccgcctcca ccgtggacgc 15720cgtcatcgac agcgtggtgg ccgatgcgcg ccggtacgcc cgcgccaaga gccggcggcg 15780gcgcatcgcc cggcggcacc ggagcacccc cgccatgcgc gcggcgcgag ccttgctgcg 15840cagggccagg cgcacgggac gcagggccat gctcagggcg gccagacgcg cggcctccgg 15900cagcagcagc gccggcagga cccgcagacg cgcggccacg gcggcggcgg cggccatcgc 15960cagcatgtcc cgcccgcggc gcggcaacgt gtactgggtg cgcgacgccg ccaccggtgt 16020gcgcgtgccc gtgcgcaccc gcccccctcg cacttgaaga tgctgacttc gcgatgttga 16080tgtgtcccag cggcgaggag gatgtccaag cgcaaataca aggaagagat gctccaggtc 16140atcgcgcctg agatctacgg ccccgcggtg aaggaggaaa gaaagccccg caaactgaag 16200cgggtcaaaa aggacaaaaa ggaggaggaa gatgtggacg gactggtgga gtttgtgcgc 16260gagttcgccc cccggcggcg cgtgcagtgg cgcgggcgga aagtgaaacc ggtgctgcgg 16320cccggcacca cggtggtctt cacgcccggc gagcgttccg gctccgcctc caagcgctcc 16380tacgacgagg tgtacgggga cgaggacatc ctcgagcagg cggtcgagcg tctgggcgag 16440
tttgcttacg gcaagcgcag ccgccccgcg cccttgaaag aggaggcggt gtccatcccg 16500ctggaccacg gcaaccccac gccgagcctg aagccggtga ccctgcagca ggtgctgccg 16560agcgcggcgc cgcgccgggg cttcaagcgc gagggcggcg aggatctgta cccgaccatg 16620cagctgatgg tgcccaagcg ccagaagctg gaggacgtgc tggagcacat gaaggtggac 16680cccgaggtgc agcccgaggt caaggtgcgg cccatcaagc aggtggcccc gggcctgggc 16740gtgcagaccg tggacatcaa gatccccacg gagcccatgg aaacgcagac cgagcccgtg 16800aagcccagca ccagcaccat ggaggtgcag acggatccct ggatgccggc gccggcttcc 16860accactcgcc gaagacgcaa gtacggcgcg gccagcctgc tgatgcccaa ctacgcgctg 16920catccttcca tcatccccac gccgggctac cgcggcacgc gcttctaccg cggctacacc 16980agcagccgcc gcaagaccac cacccgccgc cgccgtcgtc gcacccgccg cagcagcacc 17040gcgacttccg ccgccgccct ggtgcggaga gtgtaccgca gcgggcgcga gcctctgacc 17100ctgccgcgcg cgcgctacca cccgagcatc gccatttaac tctgccgtcg cctcctactt 17160gcagatatgg ccctcacatg ccgcctccgc gtccccatta cgggctaccg aggaagaaag 17220ccgcgccgta gaaggctgac ggggaacggg ctgcgtcgcc atcaccaccg gcggcggcgc 17280gccatcagca agcggttggg gggaggcttc ctgcccgcgc tgatccccat catcgccgcg 17340gcgatcgggg cgatccccgg catagcttcc gtggcggtgc aggcctctca gcgccactga 17400gacacagctt ggaaaatttg taataaaaaa atggactgac gctcctggtc ctgtgatgtg 17460tgtttttaga tggaagacat caatttttcg tccctggcac cgcgacacgg cacgcggccg 17520tttatgggca cctggagcga catcggcaac agccaactga acgggggcgc cttcaattgg 17580agcagtctct ggagcgggct taagaatttc gggtccacgc tcaaaaccta tggcaacaag 17640gcgtggaaca gcagcacagg gcaggcgctg agggaaaagc tgaaagagca gaacttccag 17700cagaaggtgg tcgatggcct ggcctcgggc atcaacgggg tggtggacct ggccaaccag 17760gccgtgcaga aacagatcaa cagccgcctg gacgcggtcc cgcccgcggg gtccgtggag 17820atgccccagg tggaggagga gctgcctccc ctggacaagc gcggcgacaa gcgaccgcgt 17880cccgacgcgg aggagacgct gctgacgcac acggacgagc cgcccccgta cgaggaggcg 17940gtgaaactgg gtctgcccac cacgcggccc gtggcgcctc tggccaccgg ggtgctgaaa 18000cccagcagca gcagccagcc cgcgaccctg gacttgcctc cgcctgcttc ccgcccctcc 18060acagtggcta agcccctgcc gccggtggcc gtcgcgtcgc gcgccccccg aggccgcccc 18120caggcgaact ggcagagcac tctgaacagc atcgtgggtc tgggagtgca gagtgtgaag 18180cgccgccgct gctattaaaa gacactgtag cgcttaactt gcttgtctgt gtgtatatgt 18240atgtccgccg accagaagga ggaagaggcg cgtcgccgag ttgcaagatg gccaccccat 18300cgatgctgcc ccagtgggcg tacatgcaca tcgccggaca ggacgcttcg gagtacctga 18360gtccgggtct ggtgcagttc gcccgcgcca cagacaccta cttcagtctg gggaacaagt 18420ttaggaaccc cacggtggcg cccacgcacg atgtgaccac cgaccgcagc cagcggctga 18480cgctgcgctt cgtgcccgtg gaccgcgagg acaacaccta ctcgtacaaa gtgcgctaca 18540
cgctggccgt gggcgacaac cgcgtgctgg acatggccag cacctacttt gacatccgcg 18600gcgtgctgga tcgggggccc agcttcaaac cctactccgg caccgcctac aacagcctgg 18660ctcccaaggg agcgcccaac acttgccagt ggacatataa agctggtgat actgatacag 18720aaaaaaccta tacatatgga aatgcacctg tgcaaggcat tagcattaca aaggatggta 18780ttcaacttgg aactgacagc gatggtcagg caatctatgc agacgaaact tatcaaccag 18840agcctcaagt gggtgatgct gaatggcatg acatcactgg tactgatgaa aaatatggag 18900gcagagctct taagcctgac accaaaatga agccttgcta tggttctttt gccaagccta 18960ccaataaaga aggaggccag gcaaatgtga aaaccgaaac aggcggtacc aaagaatatg 19020acattgacat ggcattcttc gataatcgaa gtgcagctgc cgccggccta gccccagaaa 19080ttgttttgta tactgagaat gtggatctgg aaactccaga tacccatatt gtatacaagg 19140caggtacaga tgacagtagc tcttctatca atttgggtca gcagtccatg cccaacagac 19200ccaactacat tggcttcaga gacaacttta tcggtctgat gtactacaac agcactggca 19260atatgggtgt actggctgga caggcctccc agctgaatgc tgtggtggac ttgcaggaca 19320gaaacaccga actgtcctac cagctcttgc ttgactctct gggtgacaga accaggtatt 19380tcagtatgtg gaatcaggcg gtggacagtt atgaccccga tgtgcgcatt attgaaaatc 19440acggtgtgga ggatgaactt cctaactatt gcttccccct ggatgctgtg ggtagaactg 19500atacttacca gggaattaag gccaatggtg ataatcaaac cacctggacc aaagatgata 19560ctgttaatga tgctaatgaa ttgggcaagg gcaatccttt cgccatggag atcaacatcc 19620aggccaacct gtggcggaac ttcctctacg cgaacgtggc gctgtacctg cccgactcct 19680acaagtacac gccggccaac atcacgctgc ccaccaacac caacacctac gattacatga 19740acggccgcgt ggtggcgccc tcgctggtgg acgcctacat caacatcggg gcgcgctggt 19800cgctggaccc catggacaac gtcaacccct tcaaccacca ccgcaacgcg ggcctgcgat 19860accgctccat gctcctgggc aacgggcgct acgtgccctt ccacatccag gtgccccaaa 19920agtttttcgc catcaagagc ctcctgctcc tgcccgggtc ctacacctac gagtggaact 19980tccgcaagga cgtcaacatg atcctgcaga gctccctcgg caacgacctg cgcacggacg 20040gggcctccat cgccttcacc agcatcaacc tctacgccac cttcttcccc atggcgcaca 20100acaccgcctc cacgctcgag gccatgctgc gcaacgacac caacgaccag tccttcaacg 20160actacctctc ggcggccaac atgctctacc ccatcccggc caacgccacc aacgtgccca 20220tctccatccc ctcgcgcaac tgggccgcct tccgcggctg gtccttcacg cgcctcaaga 20280cccgcgagac gccctcgctc ggctccgggt tcgaccccta cttcgtctac tcgggctcca 20340tcccctacct cgacggcacc ttctacctca accacacctt caagaaggtc tccatcacct 20400tcgactcctc cgtcagctgg cccggcaacg accgcctcct gacgcccaac gagttcgaaa 20460tcaagcgcac cgtcgacgga gaggggtaca acgtggccca gtgcaacatg accaaggact 20520ggttcctggt ccagatgctg gcccactaca acatcggcta ccagggcttc tacgtgcccg 20580agggctacaa ggaccgcatg tactccttct tccgcaactt ccagcccatg agccgccagg 20640
tcgtggacga ggtcaactac aaggactacc aggccgtcac cctggcctac cagcacaaca 20700actcgggctt cgtcggctac ctcgcgccca ccatgcgcca gggccagccc taccccgcca 20760actaccccta cccgctcatc ggcaagagcg ccgtcgccag cgtcacccag aaaaagttcc 20820tctgcgaccg ggtcatgtgg cgcatcccct tctccagcaa cttcatgtcc atgggcgcgc 20880tcaccgacct cggccagaac atgctctacg ccaactccgc ccacgcgcta gacatgaatt 20940tcgaagtcga ccccatggat gagtccaccc ttctctatgt tgtcttcgaa gtcttcgacg 21000tcgtccgagt gcaccagccc caccgcggcg tcatcgaggc cgtctacctg cgcacgccct 21060tctcggccgg caacgccacc acctaagcct cttgcttctt gcaagatgac ggcctgcgcg 21120ggctccggcg agcaggagct cagggccatc ctccgcgacc tgggctgcgg gccctgcttc 21180ctgggcacct tcgacaagcg cttcccggga ttcatggccc cgcacaagct ggcctgcgcc 21240atcgtcaaca cggccggccg cgagaccggg ggcgagcact ggctggcctt cgcctggaac 21300ccgcgctccc acacctgcta cctcttcgac cccttcgggt tctcggacga gcgcctcaag 21360cagatctacc agttcgagta cgagggcctg ctgcgtcgca gcgccctggc caccgaggac 21420cgctgcgtca ccctggaaaa gtccacccag accgtgcagg gtccgcgctc ggccgcctgc 21480gggctcttct gctgcatgtt cctgcacgcc ttcgtgcact ggcccgaccg ccccatggac 21540aagaacccca ccatgaactt gctgacgggg gtgcccaacg gcatgctcca gtcgccccag 21600gtggaaccca ccctgcgccg caaccaggag gcgctctacc gcttcctcaa cgcccactcc 21660gcctactttc gctcccaccg cgcgcgcatc gagaaggcca ccgccttcga ccgcatgaat 21720caagacatgt aatccggtgt gtgtatgtga atgctttatt catcataata aacagcacat 21780gtttatgcca ccttctctga ggctctgact ttatttagaa atcgaagggg ttctgccggc 21840tctcggcatg gcccgcgggc agggatacgt tgcggaactg gtacttgggc agccacttga 21900actcggggat cagcagcttc ggcacgggga ggtcggggaa cgagtcgctc cacagcttgc 21960gcgtgagttg cagggcgccc agcaggtcgg gcgcggagat cttgaaatcg cagttgggac 22020ccgcgttctg cgcgcgagag ttacggtaca cggggttgca gcactggaac accatcaggg 22080ccgggtgctt cacgctcgcc agcaccgtcg cgtcggtgat gccctccacg tccagatcct 22140cggcgttggc catcccgaag ggggtcatct tgcaggtctg ccgccccatg ctgggcacgc 22200agccgggctt gtggttgcaa tcgcagtgca gggggatcag catcatctgg gcctgctcgg 22260agctcatgcc cgggtacatg gccttcatga aagcctccag ctggcggaag gcctgctgcg 22320ccttgccgcc ctcggtgaag aagaccccgc aggacttgct agagaactgg ttggtggcgc 22380agccagcgtc gtgcacgcag cagcgcgcgt cgttgttggc cagctgcacc acgctgcgcc 22440cccagcggtt ctgggtgatc ttggcccggt cggggttctc cttcagcgcg cgctgcccgt 22500tctcgctcgc cacatccatc tcgatcgtgt gctccttctg gatcatcacg gtcccgtgca 22560ggcaccgcag cttgccctcg gcctcggtgc acccgtgcag ccacagcgcg cagccggtgc 22620tctcccagtt cttgtgggcg atctgggagt gcgagtgcac gaagccctgc aggaagcggc 22680ccatcatcgt ggtcagggtc ttgttgctgg tgaaggtcag cggaatgccg cggtgctcct 22740
cgttcacata caggtggcag atacggcggt acacctcgcc ctgctcgggc atcagctgga 22800aggcggactt caggtcgctc tccacgcggt accggtccat cagcagcgtc atcacttcca 22860tgcccttctc ccaggccgaa acgatcggca ggctcagggg gttcttcacc gttgtcatct 22920tagtcgccgc cgccgaagtc agggggtcgt tctcgtccag ggtctcaaac actcgcttgc 22980cgtccttctc ggtgatgcgc acggggggaa agctgaagcc cacggccgcc agctcctcct 23040cggcctgcct ttcgtcctcg ctgtcctggc tgatgtcttg caaaggcaca tgcttggtct 23100tgcggggttt ctttttgggc ggcagaggcg gcggcggaga cgtgctgggc gagcgcgagt 23160tctcgctcac cacgactatt tcttctcctt ggccgtcgtc cgagaccacg cggcggtagg 23220catgcctctt ctggggcaga ggcggaggcg acgggctctc gcggttcggc gggcggctgg 23280cagagcccct tccgcgttcg ggggtgcgct cctggcggcg ctgctctgac tgacttcctc 23340cgcggccggc cattgtgttc tcctagggag caagcatgga gactcagcca tcgtcgccaa 23400catcgccatc tgcccccgcc gccgccgacg agaaccagca gcagcagaat gaaagcttaa 23460ccgccccgcc gcccagcccc acctccgacg ccgcagcccc agacatgcaa gagatggagg 23520aatccatcga gattgacctg ggctacgtga cgcccgcgga gcacgaggag gagctggcag 23580cgcgcttttc agccccggaa gagaaccacc aagagcagcc agagcaggaa gcagagagcg 23640agcagaacca ggctgggctc gagcatggcg actacctgag cggggcagag gacgtgctca 23700tcaagcatct ggcccgccaa tgcatcatcg tcaaggacgc gctgctcgac cgcgccgagg 23760tgcccctcag cgtggcggag ctcagccgcg cctacgagcg caacctcttc tcgccgcgcg 23820tgccccccaa gcgccagccc aacggcacct gcgagcccaa cccgcgcctc aacttctacc 23880cggtcttcgc ggtgcccgag gccctggcca cctaccacct ctttttcaag aaccaaagga 23940tccccgtctc ctgccgcgcc aaccgcaccc gcgccgacgc cctgctcaac ctgggccccg 24000gcgcccgcct acctgatatc gcctccttgg aagaggttcc caagatcttc gagggtctgg 24060gcagcgacga gactcgggcc gcgaacgctc tgcaaggaag cggagaggag catgagcacc 24120acagcgccct ggtggagttg gaaggcgaca acgcgcgcct ggcggtcctc aagcgcacgg 24180tcgagctgac ccacttcgcc tacccggcgc tcaacctgcc ccccaaggtc atgagcgccg 24240tcatggacca ggtgctcatc aagcgcgcct cgcccctctc ggaggaggag atgcaggacc 24300ccgagagctc ggacgagggc aagcccgtgg tcagcgacga gcagctggcg cgctggctgg 24360gagagcagtc aggcagagga ggaggagatg gaagactggg acagcactca ggcagaggag 24420gagcgagtag caccccccag agcctggaag agcggcgcaa gctcatgatg gccgtggtcc 24480tggtgaccgt ggagctggag tgtctgcgcc gcttcttcgc cgacgcggag accctgcgca 24540aggtcgagga gaacctgcac tacctcttca gacacgggtt cgtgcgccag gcctgcaaga 24600tctccaacgt ggagctgacc aacctggtct cctacatggg catcctgcac gagaaccgcc 24660tggggcagaa cgtgctgcac accaccctgc gcggggaggc ccgccgcgac tacatccgcg 24720actgcgtcta cctgtacctc tgccacacct ggcagacggg catgggcgtg tggcagcagt 24780gcctggagga gcagaacctg aaagagctct gcaagctcct gcagaagaac ctcaaggccc 24840
tgtggaccgg gttcgacgag cgcaccaccg ccgcggacct ggccgacctc atcttccccg 24900agcgcctgcg gctgacgctg cgcaacgggc tgcccgactt tatgagccaa agcatgttgc 24960aaaactttcg ctctttcatc ctcgaacgct ccgggatcct gcccgccacc tgctccgcgc 25020tgccctcgga cttcgtgccg ctgaccttcc gcgagtgccc cccgccgctc tggagccact 25080gctacctgct gcgcctggcc aactacctgg cctaccactc ggacgtgatc gaggacgtca 25140gcggcgaggg cctgctcgag tgccactgcc gctgcaacct ctgcacgccg caccgctccc 25200tggcctgcaa cccccagctg ctgagcgaga cccagatcat cggcaccttc gagttgcaag 25260gccccggcga gggcaagggg ggtctgaaac tcaccccggg gctgtggacc tcggcctact 25320tgcgcaagtt cgtgcccgag gactaccatc ccttcgagat caggttctac gaggaccaat 25380cccagccgcc caaggccgag ctgtcggcct gcgtcatcac ccagggggcc atcctggccc 25440aattgcaagc catccagaaa tcccgccaag aatttctgct gaaaaagggc cacggggtct 25500acttggaccc ccagaccgga gaggagctca accccagctt cccccaggat gccccgagga 25560agcagcaaga agctgaaagt ggagctgccg ccgccgccgg aggatttgga ggaagactgg 25620gacagcctgc aagacagtct ggaggaggaa gacgaggtgg aggaggcaga ggaagaagca 25680gccgccgcca gaccgtcgtc ctcggcggag gaggagaaag caagcagcac ggataccatc 25740tccgctccgg gtcggggtcg cggcggccgg gcccacagta gatgggacga gaccgggcgc 25800ttcccgaacc ccaccaccca gaccggtaag aaggagcggc agggatacaa gtcctggcgg 25860gggcacaaaa acgccatcgt ctcctgcttg caagcctgcg ggggcaacat ctccttcacc 25920cggcgctacc tgctcttcca ccgcggggtg aacttccccc gcaacatctt gcattactac 25980cgtcacctcc acagccccta ctactgtttc caagaagagg cagaaaccca gcagcagcag 26040cagcagcaga aaaccagcgg cagcagctag aaaatccaca gcggcggcag gtggactgag 26100gatcgcggcg aacgagccgg cgcagacccg ggagctgagg aaccggatct ttcccaccct 26160ctatgccatc ttccagcaga gtcgggggca agagcaggaa ctgaaagtca agaaccgttc 26220tctgcgctcg ctcacccgca gttgtctgta tcacaagagc gaagaccaac ttcagcgcac 26280tctcgaggac gccgaggctc tcttcaacaa gtactgcgcg ctcactctta aagagtagcc 26340cgcgcccgcc cacacacgga aaaaggcggg aattacgtca ccacctgcgc ccttcgcccg 26400accatcatca tgagcaaaga gattcccacg ccttacatgt ggagctacca gccccagatg 26460ggcctggccg ccggcgccgc ccaggactac tccacccgca tgaactggct cagtgccggg 26520cccgcgatga tctcacgggt gaatgacatc cgcgcccacc gaaaccagat actcctagaa 26580cagtcagcga tcaccgccac gccccgccat caccttaatc cgcgtaattg gcccgccgcc 26640ctggtgtacc aggaaattcc ccagcccacg accgtactac ttccgcgaga cgcccaggcc 26700gaagtccagc tgactaactc aggtgtccag ctggccggcg gcgccgccct gtgtcgtcac 26760cgccccgctc agggtataaa gcggctggtg atccgaggca gaggcacaca gctcaacgac 26820gaggtggtga gctcttcgct gggtctgcga cctgacggag tcttccaact cgccggatcg 26880gggagatctt ccttcacgcc tcgtcaggcc gtcctgactt tggagagttc gtcctcgcag 26940
ccccgctcgg gtggcatcgg cactctccag ttcgtggagg agttcactcc ctcggtctac 27000ttcaacccct tctccggctc ccccggccac tacccggacg agttcatccc gaacttcgac 27060gccatcagcg agtcggtgga cggctacgat tgaatgtccc atggtggcgc ggctgaccta 27120gctcggcttc gacacctgga ccactgccgc cgcttccgct gcttcgctcg ggatctcgcc 27180gagtttgcct actttgagct gcccgaggag caccctcagg gcccggccca cggagtgcgg 27240atcgtcgtcg aagggggtct cgactcccac ctgcttcgga tcttcagcca gcgtccgatc 27300ctggccgagc gcgagcaagg acagaccctt ctgaccctgt actgcatctg caaccacccc 27360ggcctgcatg aaagtctttg ttgtctgctg tgtactgagt ataataaaag ctgagatcag 27420cgactactcc ggacttccgt gtgttcctgc tatcaaccag tccctgttct tcaccgggaa 27480cgagaccgag ctccagctcc agtgtaagcc ccacaagaag tacctcacct ggctgttcca 27540gggctctccg atcgccgttg tcaaccactg cgacaacgac ggagtcctgc tgagcggccc 27600tgccaacctt actttttcca cccgcagaag caagctccag ctcttccaac ccttcctccc 27660cgggacctat cagtgcgtct cgggaccctg ccatcacacc ttccacctga tcccgaatac 27720cacagcgtcg ctccccgcta ctaacaacca aactacccac caacgccacc gtcgcgacct 27780ttcctctggg tctaatacca ctaccggagg tgagctccga ggtcgaccaa cctctgggat 27840ttactacggc ccctgggagg tggtagggtt aatagcgcta ggcctagttg cgggtgggct 27900tttggctctc tgctacctat acctcccttg ctgttcgtac ttagtggtgc tgtgttgctg 27960gtttaagaaa tggggaagat caccctagtg agctgcggtg tgctggtggc ggtggtgctt 28020tcgattgtgg gactgggcgg cgcggctgta gtgaaggaga aggccgatcc ctgcttgcat 28080ttcaatcccg acaaatgcca gctgagtttt cagcccgatg gcaatcggtg cgcggtgctg 28140atcaagtgcg gatgggaatg cgagaacgtg agaatcgagt acaataacaa gactcggaac 28200aatactctcg cgtccgtgtg gcagcccggg gaccccgagt ggtacaccgt ctctgtcccc 28260ggtgctgacg gctccccgcg caccgtgaat aatactttca tttttgcgca catgtgcgac 28320acggtcatgt ggatgagcaa gcagtacgat atgtggcccc ccacgaagga gaacatcgtg 28380gtcttctcca tcgcttacag cgtgtgcacg gcgctaatca ccgctatcgt gtgcctgagc 28440attcacatgc tcatcgctat tcgccccaga aataatgccg aaaaagaaaa acagccataa 28500cacgtttttt cacacacctt tttcagacca tggcctctgt taaatttttg cttttatttg 28560ccagtctcat tgccgtcatt catggaatga gtaatgagaa aattactatt tacactggca 28620ctaatcacac attgaaaggt ccagaaaaag ccacagaagt ttcatggtat tgttatttta 28680atgaatcaga tgtatctact gaactctgtg gaaacaataa caaaaaaaat gagagcatta 28740ctctcatcaa gtttcaatgt ggatctgact taaccctaat taacatcact agagactatg 28800taggtatgta ttatggaact acagcaggca tttcggacat ggaattttat caagtttctg 28860tgtctgaacc caccacgcct agaatgacca caaccacaaa aactacacct gttaccacta 28920tacagctcac taccaatggc tttcttgcca tgcttcaagt ggctgaaaat agcaccagca 28980ttcaacccac cccacccagt gaggaaattc ccagatccat gattggcatt attgttgctg 29040
tagtggtgtg catgttgatc atcgccttgt gcatggtgta ctatgccttc tgctacagaa 29100agcacagact gaacgacaag ctggaacact tactaagtgt tgaattttaa ttttttagaa 29160ccatgaagat cctaggcctt ttagtttttt ctatcattac ctctgctcta tgcaattctg 29220acaatgagga cgttactgtc gttgtcggat caaattatac actaaaaggt ccagcaaaag 29280gtatgctttc gtggtattgt tggttcggaa ctgacgagca acagacagaa ctttgcaatg 29340ctcaaaaagg caaaacctca aattctaaaa tctctaatta tcaatgcaat ggcactgact 29400tagtattgct caatgtcacg aaagcatatg ctggcagtta cacctgccct ggagatgatg 29460ccgacaatat gattttttac aaagtggaag tggttgatcc cactactcca ccgcccacca 29520ccacaactac tcataccaca cacacagaac aaacaccaga ggcagcagaa gcagagttgg 29580ccttccaggt tcacggagat tcctttgctg tcaatacccc tacacccgat cagcggtgtc 29640cggggctgct cgtcagcggc attgtcggtg tgctttcggg attagcagtc ataatcatct 29700gcatgttcat ttttgcttgc tgctatagaa ggctttaccg acaaaaatca gacccactgc 29760tgaacctcta tgtttaattt tttccagagc catgaaggca gttagcgctc tagttttttg 29820ttctttgatt ggcattgttt ttagtgctgg gtttttgaaa aatcttacca tttatgaagg 29880tgagaatgcc actctagtgg gcatcagtgg tcaaaatgtc agctggctaa aataccatct 29940agatgggtgg aaagacattt gcgattggaa tgtcactgtg tatacatgta atggagttaa 30000cctcaccatt actaatgcca cccaagatca gaatggtagg tttaagggcc agagtttcac 30060tagaaataat gggtatgaat cccataacat gtttatctat gacgtcactg tcatcagaaa 30120tgagactgcc accaccacac agatgcccac tacacacagt tctaccacta ctaccatgca 30180aaccacacag acaaccacta catcaactca gcatatgacc accactacag cagcaaagcc 30240aagtagtgca gcgcctcagc cccaggcttt ggctttgaaa gctgcacaac ctagtacaac 30300tactaggacc aatgagcaga ctactgaatt tttgtccact gtcgagagcc acaccacagc 30360tacctccagt gccttctcta gcaccgccaa tctctcctcg ctttcctcta caccaatcag 30420tcccgctact actcccaccc cagctcttct ccccactccc ctgaagcaaa ctgaggacag 30480cggcatgcaa tggcagatca ccctgctcat tgtgatcggg ttggtcatcc tggccgtgtt 30540gctctactac atcttctgcc gccgcattcc caacgcgcac cgcaaaccgg cctacaagcc 30600catcgttatc gggcagccgg agccgcttca ggtggaaggg ggtctaagga atcttctctt 30660ctcttttaca gtatggtgat tgaactatga ttcctagaca attcttgatc actattctta 30720tctgcctcct ccaagtctgt gccaccctcg ctctggtggc caacgccagt ccagactgta 30780ttgggccctt cgcctcctac gtgctctttg ccttcatcac ctgcatctgc tgctgtagca 30840tagtctgcct gcttatcacc ttcttccagt tcattgactg gatctttgtg cgcatcgcct 30900acctgcgcca ccacccccag taccgcgacc agcgagtggc gcggctgctc aggctcctct 30960gataagcatg cgggctctgc tacttctcgc gcttctgctg ttagtgctcc cccgccccgt 31020cgacccccgg tcccccactc agtcccccga agaggtccgc aaatgcaaat tccaagaacc 31080ctggaaattc ctcaaatgct accgccaaaa atcagacatg cttcccagct ggatcatgat 31140
cattgggatc gtgaacattc tggcctgcac cctcatctcc tttgtgattt acccctgctt 31200tgactttggt tggaactcgc cagaggcgct ctatctcccg cctgaacctg acacaccacc 31260acagcaacct caggcacacg cactaccacc accacagcct aggccacaat acatgcccat 31320attagactat gaggccgagc cacagcgacc catgctcccc gctattagtt acttcaatct 31380aaccggcgga gatgactgac ccactggcca acaacaacgt caacgacctt ctcctggaca 31440tggacggccg cgcctcggag cagcgactcg cccaacttcg cattcgccag cagcaggaga 31500gagccgtcaa ggagctgcag gacggcatag ccatccacca gtgcaagaaa ggcatcttct 31560gcctggtgaa acaggccaag atctcctacg aggtcacccc gaccgaccat cgcctctcct 31620acgagctcct gcagcagcgc cagaagttca cctgcctggt cggagtcaac cccatcgtca 31680tcacccagca gtcgggcgat accaaggggt gcatccactg ctcctgcgac tcccccgact 31740gcgtccacac tctgatcaag accctctgcg gcctccgcga cctcctcccc atgaactaat 31800caccccctta tccagtgaaa taaatatcat attgatgatg atttaaataa aaaataatca 31860tttgatttga aataaagata caatcatatt gatgatttga gttttaaaaa ataaagaatc 31920acttacttga aatctgatac caggtctctg tccatgtttt ctgccaacac cacctcactc 31980ccctcttccc agctctggta ctgcagaccc cggcgggctg caaacttcct ccacacgctg 32040aaggggatgt caaattcctc ctgtccctca atcttcattt tatcttctat cagatgtcca 32100aaaagcgcgt ccgggtggat gatgacttcg accccgtcta cccctacgat gcagacaacg 32160caccgaccgt gcccttcatc aaccccccct tcgtctcttc agatggattc caagagaagc 32220ccctgggggt gctgtccctg cgactggctg accccgtcac caccaagaac ggggaaatca 32280ccctcaagct gggagagggg gtggacctcg actcctcggg aaaactcatc tccaacacgg 32340ccaccaaggc cgccgcccct ctcagttttt ccaacaacac catttccctt aacatggata 32400cccctcttta taccaaagat ggaaaattat ccttacaagt ttctccaccg ttaaacatat 32460taaaatcaac cattctgaac acattagctg tagcttatgg atcaggttta ggactgagtg 32520gtggcactgc tcttgcagta cagttggcct ctccactcac ttttgatgaa aaaggaaata 32580ttaaaattaa cctagccagt ggtccattaa cagttgatgc aagtcgactt agtatcaact 32640gcaaaagagg ggtcactgtc actacctcag gagatgcaat tgaaagcaac ataagctggc 32700ctaaaggtat aagatttgaa ggtaatggca tagctgcaaa cattggcaga ggattggaat 32760ttggaaccac tagtacagag actgatgtca cagatgcata cccaattcaa gttaaattgg 32820gtactggcct tacctttgac agtacaggcg ccattgttgc ttggaacaaa gaggatgata 32880aacttacatt atggaccaca gccgacccct cgccaaattg caaaatatac tctgaaaaag 32940atgccaaact cacactttgc ttgacaaagt gtggaagtca aattctgggt actgtgactg 33000tattggcagt gaataatgga agtctcaacc caatcacaaa cacagtaagc actgcactcg 33060tctccctcaa gtttgatgca agtggagttt tgctaagcag ctccacatta gacaaagaat 33120attggaactt cagaaaggga gatgttacac ctgctgagcc ctatactaat gctataggtt 33180ttatgcctaa cataaaggcc tatcctaaaa acacatctgc agcttcaaaa agccatattg 33240
tcagtcaagt ttatctcaat ggggatgagg ccaaaccact gatgctgatt attactttta 33300atgaaactga ggatgcaact tgcacctaca gtatcacttt tcaatggaaa tgggatagta 33360ctaagtacac aggtgaaaca cttgctacca gctccttcac cttctcctac atcgcccaag 33420aatgaacact gtatcccacc ctgcatgcca acccttccca ccccactctg tctatggaaa 33480aaactctgaa gcacaaaata aaataaagtt caagtgtttt attgattcaa cagttttaca 33540ggattcgagc agttattttt cctccaccct cccaggacat ggaatacacc accctctccc 33600cccgcacagc cttgaacatc tgaatgccat tggtgatgga catgcttttg gtctccacgt 33660tccacacagt ttcagagcga gccagtctcg ggtcggtcag ggagatgaaa ccctccgggc 33720actcccgcat ctgcacctca cagctcaaca gctgaggatt gtcctcggtg gtcgggatca 33780cggttatctg gaagaagcag aagagcggcg gtgggaatca tagtccgcga acgggatcgg 33840ccggtggtgt cgcatcaggc cccgcagcag tcgctgccgc cgccgctccg tcaagctgct 33900gctcaggggg tccgggtcca gggactccct cagcatgatg cccacggccc tcagcatcag 33960tcgtctggtg cggcgggcgc agcagcgcat gcggatctcg ctcaggtcgc tgcagtacgt 34020gcaacacagg accaccaggt tgttcaacag tccatagttc aacacgctcc agccgaaact 34080catcgcggga aggatgctac ccacgtggcc gtcgtaccag atcctcaggt aaatcaagtg 34140gcgctccctc cagaacacgc tgcccacgta catgatctcc ttgggcatgt ggcggttcac 34200cacctcccgg taccacatca ccctctggtt gaacatgcag ccccggatga tcctgcggaa 34260ccacagggcc agcaccgccc cgcccgccat gcagcgaaga gaccccgggt cccggcaatg 34320gcaatggagg acccaccgct cgtacccgtg gatcatctgg gagctgaaca agtctatgtt 34380ggcacagcac aggcatatgc tcatgcatct cttcagcact ctcagctcct cgggggtcaa 34440aaccatatcc cagggcacgg ggaactcttg caggacagcg aaccccgcag aacagggcaa 34500tcctcgcaca taacttacat tgtgcatgga cagggtatcg caatcaggca gcaccgggtg 34560atcctccacc agagaagcgc gggtctcggt ctcctcacag cgtggtaagg gggccggccg 34620atacgggtga tggcgggacg cggctgatcg tgttcgcgac cgtgtcatga tgcagttgct 34680ttcggacatt ttcgtacttg ctgtagcaga acctggtccg ggcgctgcac accgatcgcc 34740ggcggcggtc ccggcgcttg gaacgctcgg tgttgaaatt gtaaaacagc cactctctca 34800gaccgtgcag cagatctagg gcctcaggag tgatgaagat cccatcatgc ctgatagctc 34860tgatcacatc gaccaccgtg gaatgggcca gacccagcca gatgatgcaa ttttgttggg 34920tttcggtgac ggcgggggag ggaagaacag gaagaaccat gattaacttt taatccaaac 34980ggtctcggag cacttcaaaa tgaaggtcgc ggagatggca cctctcgccc ccgctgtgtt 35040ggtggaaaat aacagccagg tcaaaggtga tacggttctc gagatgttcc acggtggctt 35100ccagcaaagc ctccacgcgc acatccagaa acaagacaat agcgaaagcg ggagggttct 35160ctaattcctc aatcatcatg ttacactcct gcaccatccc cagataattt tcatttttcc 35220agccttgaat gattcgaact agttcctgag gtaaatccaa gccagccatg ataaagagct 35280cgcgcagagc gccctccacc ggcattctta agcacaccct cataattcca agatattctg 35340
ctcctggttc acctgcagca gattgacaag cggaatatca aaatctctgc cgcgatccct 35400aagctcctcc ctcagcaata actgtaagta ctctttcata tcctctccga aatttttagc 35460cataggacca ccaggaataa gattagggca agccacagta cagataaacc gaagtcctcc 35520ccagtgagca ttgccaaatg caagactgct ataagcatgc tggctagacc cggtgatatc 35580ttccagataa ctggacagaa aatcacccag gcaattttta agaaaatcaa caaaagaaaa 35640atcctccagg tgcacgttta gagcctcggg aacaacgatg aagtaaatgc aagcggtgcg 35700ttccagcatg gttagttagc tgatctgtaa aaaacaaaaa ataaaacatt aaaccatgct 35760agcctggcga acaggtgggt aaatcgttct ctccagcacc aggcaggcca cggggtctcc 35820ggcgcgaccc tcgtaaaaat tgtcgctatg attgaaaacc atcacagaga gacgttcccg 35880gtggccggcg tgaatgattc gacaagatga atacaccccc ggaacattgg cgtccgcgag 35940tgaaaaaaag cgcccgagga agcaataagg cactacaatg ctcagtctca agtccagcaa 36000agcgatgcca tgcggatgaa gcacaaaatc ctcaggtgcg tacaaaatgt aattactccc 36060ctcctgcaca ggcagcgaag cccccgatcc ctccagatac acatacaaag cctcagcgtc 36120catagcttac cgagcagcag cacacaacag gcgcaagagt cagagaaagg ctgagctcta 36180acctgtccac ccgctctctg ctcaatatat agcccagatc tacactgacg taaaggccaa 36240agtctaaaaa tacccgccaa ataatcacac acgcccagca cacgcccaga aaccggtgac 36300acactcaaaa aaatacgcgc acttcctcaa acgcccaaac tgccgtcatt tccgggttcc 36360cacgctacgt catcggaatt cgactttcaa attccgtcga ccgttaaaaa cgtcacccgc 36420cccgccccta acggtcgccc gtctctcggc caatcacctt cctccctccc caaattcaaa 36480cagctcattt gcatattaac gcgcaccaaa agtttgaggt atattattga tgatg 36535210521132020212DNA213黑猩猩Pan 5(CV23)基因組4005catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg aggtatttga 60atttggggat gcggggcggt gattggctgc gggagcggcg accgttaggg gcggggcggg 120tgacgttttg atgacgtggc cgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300aatgaggaag tgaaaatctg agtaattccg cgtttatggc agggaggagt atttgccgag 360ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggt gtcagctgat cgccagggta 480
tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600gtaatgtttt cctggctact gggaacgaga ttctggaact ggtggtggac gccatgatgg 660gtgacgaccc tccggagccc cctaccccat ttgaagcgcc ttcgctgtac gatttgtatg 720atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960aggaggcgat tcgagctgca gcgaaccagg gagtgaaaac agcgagcgag ggctttagcc 1020tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140acagtaagtg tgattaactt tagctgggga ggcagagggt gactgggtgc tgactggttt 1200atttatgtat atgtttttta tgtgtaggtc ccgtctctga cgtagatgag acccccacta 1260cagagtgcat ttcatcaccc ccagaaattg gcgaggaacc gcccgaagat attattcata 1320gaccagttgc agtgagagtc accgggcgta gagcagctgt ggagagtttg gatgacttgc 1380tacagggtgg ggatgaacct ttggacttgt gtacccggaa acgccccagg cactaagtgc 1440cacacatgtg tgtttactta aggtgatgtc agtatttata gggtgtggag tgcaataaaa 1500tccgtgttga ctttaagtgc gtggtttatg actcaggggt ggggactgtg ggtatataag 1560caggtgcaga cctgtgtggt cagttcagag caggactcat ggagatctgg acagtcttgg 1620aagactttca ccagactaga cagctgctag agaactcatc ggagggagtc tcttacctgt 1680ggagattctg cttcggtggg cctctagcta agctagtcta tagggccaag caggattata 1740aggatcaatt tgaggatatt ttgagagagt gtcctggtat ttttgactct ctcaacttgg 1800gccatcagtc tcactttaac cagagtattc tgagagccct tgacttttct actcctggca 1860gaactaccgc cgcggtagcc ttttttgcct ttatccttga caaatggagt caagaaaccc 1920atttcagcag ggattaccgt ctggactgct tagcagtagc tttgtggaga acatggaggt 1980gccagcgcct gaatgcaatc tccggctact tgccagtaca gccggtagac acgctgagga 2040tcctgagtct ccagtcaccc caggaacacc aacgccgcca gcagccgcag caggagcagc 2100agcaagagga ggaccgagaa gagaacctga gagccggtct ggaccctccg gtggcggagg 2160aggaggagta gctgacttgt ttcccgagct gcgccgggtg ctgactaggt cttccagtgg 2220acgggagagg gggattaagc gggagaggca tgaggagact agccacagaa ctgaactgac 2280tgtcagtctg atgagtcgca ggcgcccaga atcggtgtgg tggcatgagg tgcagtcgca 2340ggggatagat gaggtctcag tgatgcatga gaaatattcc ctagaacaag tcaagacttg 2400ttggttggag cccgaggatg attgggaggt agccatcagg aattatgcca agctggctct 2460gaggccagac aagaagtaca agattaccaa actgattaat atcagaaatt cctgctacat 2520ttcagggaat ggggccgagg tggagatcag tacccaggag agggtggcct tcagatgctg 2580
catgatgaat atgtacccgg gggtggtggg catggaggga gtcaccttta tgaacgcgag 2640gttcaggggt gatgggtata atggggtggt ctttatggcc aacaccaagc tgacagtgca 2700cggatgctcc ttctttggct tcaataacat gtgcattgag gcctggggca gtgtttcagt 2760gaggggatgc agtttttcag ccaactggat gggggtcgtg ggcagaacca agagcatggt 2820gtcagtgaag aaatgcctgt tcgagaggtg ccacctgggg gtgatgagcg agggcgaagc 2880caaagtcaaa cactgcgcct ctaccgagac gggctgcttt gtactgatca agggcaatgc 2940caaagtcaag cataatatga tctgtggggc ctcggatgag cgcggctacc agatgctgac 3000ctgcgccggt gggaacagcc atatgctagc caccgtgcat gtggcctcgc acccccgcaa 3060gacatggccc gagttcgagc acaacgtcat gacccgctgc aatgtgcacc tggggtcccg 3120ccgaggcatg ttcatgccct accagtgcaa catgcaattt gtgaaggtgc tgctggagcc 3180cgatgccatg tccagagtga gcctgacggg ggtgtttgac atgaatgtgg agctgtggaa 3240aattctgaga tatgatgaat ccaagaccag gtgccgggcc tgcgaatgcg gaggcaagca 3300cgccaggctt cagcccgtgt gtgtggaggt gacggaggac ctgcgacccg atcatttggt 3360gttgtcctgc aacgggacgg agttcggctc cagcggggaa gaatctgact agagtgagta 3420gtgtttggga ctgggtggga gcctgcatga tgggcagaat gactaaaatc tgtgtttttc 3480tgcgcagcag catgagcgga agcgcctcct ttgagggagg ggtattcagc ccttatctga 3540cggggcgtct cccctcctgg gcgggagtgc gtcagaatgt gatgggatcc acggtggacg 3600gccggcccgt gcagcccgcg aactcttcaa ccctgaccta cgcgaccctg agctcctcgt 3660ccgtggacgc agctgccgcc gcagctgctg cttccgccgc cagcgccgtg cgcggaatgg 3720ccctgggcgc cggctactac agctctctgg tggccaactc gagttccacc aataatcccg 3780ccagcctgaa cgaggagaag ctgctgctgc tgatggccca gctcgaggcc ctgacccagc 3840gcctgggcga gctgacccag caggtggctc agctgcaggc ggagacgcgg gccgcggttg 3900ccacggtgaa aaccaaataa aaaatgaatc aataaataaa cggagacggt tgttgatttt 3960aacacagagt cttgaatctt tatttgattt ttcgcgcgcg gtaggccctg gaccaccggt 4020ctcgatcatt gagcacccgg tggatctttt ccaggacccg gtagaggtgg gcttggatgt 4080tgaggtacat gggcatgagc ccgtcccggg ggtggaggta gctccattgc agggcctcgt 4140gctcgggggt ggtgttgtaa atcacccagt catagcaggg gcgcagggcg tggtgctgca 4200cgatgtcctt gaggaggaga ctgatggcca cgggcagccc cttggtgtag gtgttgacga 4260acctgttgag ctgggaggga tgcatgcggg gggagatgag atgcatcttg gcctggatct 4320tgagattggc gatgttcccg cccagatccc gccgggggtt catgttgtgc aggaccacca 4380gcacggtgta tccggtgcac ttggggaatt tgtcatgcaa cttggaaggg aaggcgtgaa 4440agaatttgga gacgcccttg tgaccgccca ggttttccat gcactcatcc atgatgatgg 4500cgatgggccc gtgggcggcg gcttgggcaa agacgtttcg ggggtcggac acatcgtagt 4560tgtggtcctg ggtgagctcg tcataggcca ttttaatgaa tttggggcgg agggtgcccg 4620actgggggac gaaggtgccc tcgatcccgg gggcgtagtt gccctcgcag atctgcatct 4680
cccaggcctt gagctcggag ggggggatca tgtccacctg cggggcgatg aaaaaaacgg 4740tttccggggc gggggagatg agctgggccg aaagcaggtt ccggagcagc tgggacttgc 4800cgcagccggt ggggccgtag atgaccccga tgaccggctg caggtggtag ttgagggaga 4860gacagctgcc gtcctcgcgg aggagggggg ccacctcgtt catcatctcg cgcacatgca 4920tgttctcgcg cacgagttcc gccaggaggc gctcgccccc aagcgagagg agctcttgca 4980gcgaggcgaa gtttttcagc ggcttgagcc cgtcggccat gggcattttg gagagggtct 5040gttgcaagag ttccagacgg tcccagagct cggtgatgtg ctctagggca tctcgatcca 5100gcagacctcc tcgtttcgcg ggttggggcg actgcgggag tagggcacca ggcgatgggc 5160gtccagcgag gccagggtcc ggtccttcca ggggcgcagg gtccgcgtca gcgtggtctc 5220cgtcacggtg aaggggtgcg cgccgggctg ggcgcttgcg agggtgcgct tcaggctcat 5280ccggctggtc gagaaccgct cccggtcggc gccctgcgcg tcggccaggt agcaattgag 5340catgagttcg tagttgagcg cctcggccgc gtggcccttg gcgcggagct tacctttgga 5400agtgtgtccg cagacgggac agaggaggga cttgagggcg tagagcttgg gggcgaggaa 5460gacggactcg ggggcgtagg cgtccgcgcc gcagctggcg cagacggtct cgcactccac 5520gagccaggtg aggtctggcc ggtcggggtc aaaaacgagg tttcctccgt gctttttgat 5580gcgtttctta cctctggtct ccatgagctc gtgtccccgc tgggtgacaa agaggctgtc 5640cgtgtccccg tagaccgact ttatgggccg gtcctcgagc ggggtgccgc ggtcctcgtc 5700gtagaggaac cccgcccact ccgagacgaa ggcccgggtc caggccagca cgaaggaggc 5760cacgtgggag gggtagcggt cgttgtccac cagcgggtcc accttctcca gggtatgcaa 5820gcacatgtcc ccctcgtcca catccaggaa ggtgattggc ttgtaagtgt aggccacgtg 5880accgggggtc ccggccgggg gggtataaaa gggggcgggc ccctgctcgt cctcactgtc 5940ttccggatcg ctgtccagga gcgccagctg ttggggtagg tattccctct cgaaggcggg 6000catgacctcg gcactcaggt tgtcagtttc tagaaacgag gaggatttga tattgacggt 6060gccgttggag acgcctttca tgagcccctc gtccatctgg tcagaaaaga cgatcttttt 6120gttgtcgagc ttggtggcga aggagccgta gagggcgttg gagagcagct tggcgatgga 6180gcgcatggtc tggttctttt ccttgtcggc gcgctccttg gcggcgatgt tgagctgcac 6240gtactcgcgc gccacgcact tccattcggg gaagacggtg gtgagcttgt cgggcacgat 6300tctgacccgc cagccgcggt tgtgcagggt gatgaggtcc acgctggtgg ccacctcgcc 6360gcgcaggggc tcgttggtcc agcagaggcg cccgcccttg cgcgagcaga aggggggcag 6420cgggtccagc atgagctcgt cgggggggtc ggcgtccacg gtgaagatgc cgggcaggag 6480ctcggggtcg aagtagctga tgcaggtgcc cagatcgtcc agcgccgctt gccagtcgcg 6540cacggccagc gcgcgctcgt aggggctgag gggcgtgccc cagggcatgg ggtgcgtgag 6600cgcggaggcg tacatgccgc agatgtcgta gacgtagagg ggctcctcga ggacgccgat 6660gtaggtgggg tagcagcgcc ccccgcggat gctggcgcgc acgtagtcgt acagctcgtg 6720cgagggcgcg aggagcccgg tgccgaggtt ggagcgctgc ggcttttcgg cgcggtagac 6780
gatctggcgg aagatggcgt gggagttgga ggagatggtg ggcctctgga agatgttgaa 6840gtgggcgtgg ggcagtccga ccgagtccct gatgaagtgg gcgtaggagt cctgcagctt 6900ggcgacgagc tcggcggtga cgaggacgtc cagggcgcag tagtcgaggg tctcttggat 6960gatgtcgtac ttgagctggc ccttctgctt ccacagctcg cggttgagaa ggaactcttc 7020gcggtccttc cagtactctt cgagggggaa cccgtcctga tcggcacggt aagagcccac 7080catgtagaac tggttgacgg ccttgtaggc gcagcagccc ttctccacgg ggagggcgta 7140agcttgcgcg gccttgcgca gggaggtgtg ggtgagggcg aaggtgtcgc gcaccatgac 7200cttgaggaac tggtgcttga agtcgaggtc gtcgcagccg ccctgctccc agagctggaa 7260gtccgtgcgc ttcttgtagg cggggttggg caaagcgaaa gtaacatcgt tgaagaggat 7320cttgcccgcg cggggcatga agttgcgagt gatgcggaaa ggctggggca cctcggcccg 7380gttgttgatg acctgggcgg cgaggacgat ctcgtcgaag ccgttgatgt tgtgcccgac 7440gatgtagagt tccacgaatc gcgggcggcc cttgacgtgg ggcagcttct tgagctcgtc 7500gtaggtgagc tcggcggggt cgctgaggcc gtgctgctcg agggcccagt cggcgaggtg 7560ggggttggcg ccgaggaagg aagtccagag atccacggcc agggcggtct gcaagcggtc 7620ccggtactga cggaactgct ggcccacggc cattttttcg ggggtgacgc agtagaaggt 7680gcgggggtcg ccgtgccagc ggtcccactt gagctggagg gcgaggtcgt gggcgagctc 7740gacgagcggc gggtccccgg agagtttcat gaccagcatg aaggggacga gctgcttgcc 7800gaaggacccc atccaggtgt aggtttccac gtcgtaggtg aggaagagcc tttcggtgcg 7860aggatgcgag ccgatgggga agaactggat ctcctgccac cagttggagg aatggctgtt 7920gatgtgatgg aagtagaaat gccgacggcg cgccgagcac tcgtgcttgt gtttatacaa 7980gcgtccgcag tgctcgcaac gctgcacggg atgcacgtgc tgcacgagct gtacctgggt 8040tcctttgacg aggaatttca gtgggcagtg gagcgctggc ggctgcatct ggtgctgtac 8100tacgtcctgg ccatcggcgt ggccatcgtc tgcctcgatg gtggtcatgc tgacgaggcc 8160gcgcgggagg caggtccaga cctcggctcg gacgggtcgg agagcgagga cgagggcgcg 8220caggccggag ctgtccaggg tcctgagacg ctgcggagtc aggtcagtgg gcagcggcgg 8280cgcgcggttg acttgcagga gcttttccag ggcgcgcggg aggtccagat ggtacttgat 8340ctccacggcg ccgttggtgg cgacgtccac ggcttgcagg gtcccgtgcc cctggggcgc 8400caccaccgtg ccccgtttct tcttgggtgc tggcggcggc ggctccatgc ttagaagcgg 8460cggcgaggac gcgcgccggg cggcaggggc ggctcggggc ccggaggcag gggcggcagg 8520ggcacgtcgg cgccgcgcgc gggcaggttc tggtactgcg cccggagaag actggcgtga 8580gcgacgacgc gacggttgac gtcctggatc tgacgcctct gggtgaaggc cacgggaccc 8640gtgagtttga acctgaaaga gagttcgaca gaatcaatct cggtatcgtt gacggcggcc 8700tgccgcagga tctcttgcac gtcgcccgag ttgtcctggt aggcgatctc ggtcatgaac 8760tgctcgatct cctcctcctg aaggtctccg cgaccggcgc gctcgacggt ggccgcgagg 8820tcgttggaga tgcggcccat gagctgcgag aaggcgttca tgccggcctc gttccagacg 8880
cggctgtaga ccacggctcc gtcggggtcg cgcgcgcgca tgaccacctg ggcgaggttg 8940agctcgacgt ggcgcgtgaa gaccgcgtag ttgcagaggc gctggtagag gtagttgagc 9000gtggtggcga tgtgctcggt gacgaagaag tacatgatcc agcggcggag cggcatctcg 9060ctgacgtcgc ccagggcttc caagcgctcc atggcctcgt agaagtccac ggcgaagttg 9120aaaaactggg agttgcgcgc cgagacggtc aactcctcct ccagaagacg gatgagctcg 9180gcgatggtgg cgcgcacctc gcgctcgaag gccccggggg gctcctcttc ttccatctcc 9240tcctcctctt ccatctcctc cactaacatc tcttctactt cctcctcagg aggcggcggc 9300gggggagggg ccctgcgtcg ccggcggcgc acgggcagac ggtcgatgaa gcgctcgatg 9360gtctccccgc gccggcgacg catggtctcg gtgacggcgc gcccgtcctc gcggggccgc 9420agcgtgaaga cgccgccgcg catctccagg tggccgccgg gggggtctcc gttgggcagg 9480gagagggcgc tgacgatgca tcttatcaat tggcccgtag ggactccgcg caaggacctg 9540agcgtctcga gatccacggg atccgaaaac cgctgaacga aggcttcgag ccagtcgcag 9600tcgcaaggta ggctgagccc ggtttcttgt tcttcgggta tttggtcggg aggcgggcgg 9660gcgatgctgc tggtgatgaa gttgaagtag gcggtcctga gacggcggat ggtggcgagg 9720agcaccaggt ccttgggccc ggcttgctgg atgcgcagac ggtcggccat gccccaggcg 9780tggtcctgac acctggcgag gtccttgtag tagtcctgca tgagccgctc cacgggcacc 9840tcctcctcgc ccgcgcggcc gtgcatgcgc gtgagcccga acccgcgctg cggctggacg 9900agcgccaggt cggcgacgac gcgctcggcg aggatggcct gctggatctg ggtgagggtg 9960gtctggaagt cgtcgaagtc gacgaagcgg tggtaggctc cggtgttgat ggtgtaggag 10020cagttggcca tgacggacca gttgacggtc tggtggccgg ggcgcacgag ctcgtggtac 10080ttgaggcgcg agtaggcgcg cgtgtcgaag atgtagtcgt tgcaggtgcg cacgaggtac 10140tggtatccga cgaggaagtg cggcggcggc tggcggtaga gcggccatcg ctcggtggcg 10200ggggcgccgg gcgcgaggtc ctcgagcatg aggcggtggt agccgtagat gtacctggac 10260atccaggtga tgccggcggc ggtggtggag gcgcgcggga actcgcggac gcggttccag 10320atgttgcgca gcggcaggaa gtagttcatg gtggccgcgg tctggcccgt gaggcgcgcg 10380cagtcgtgga tgctctagac atacgggcaa aaacgaaagc ggtcagcggc tcgactccgt 10440ggcctggagg ctaagcgaac gggttgggct gcgcgtgtac cccggttcga gtccctgctc 10500gaatcaggct ggagccgcag ctaacgtggt actggcactc ccgtctcgac ccaagcctgc 10560taacgaaacc tccaggatac ggaggcgggt cgttttggcc attttcgtca ggccggaaat 10620gaaactagta agcgcggaaa gcggccgtcc gcgatggctc gctgccgtag tctggagaaa 10680gaatcgccag ggttgcgttg cggtgtgccc cggttcgagc ctcagcgctc ggcgccggcc 10740ggattccgcg gctaacgtgg gcgtggctgc cccgtcgttt ccaagacccc ttagccagcc 10800gacttctcca gttacggagc gagcccctct ttttcttgtg tttttgccag atgcatcccg 10860tactgcggca gatgcgcccc caccctccac cacaaccgcc cctaccgcag cagcagcaac 10920agccggcgct tctgcccccg ccccagcagc agcagccagc cactaccgcg gcggccgccg 10980
tgagcggagc cggcgttcag tatgacctgg ccttggaaga gggcgagggg ctggcgcggc 11040tgggggcgtc gtcgccggag cggcacccgc gcgtgcagat gaaaagggac gctcgcgagg 11100cctacgtgcc caagcagaac ctgttcagag acaggagcgg cgaggagccc gaggagatgc 11160gcgcctcccg cttccacgcg gggcgggagc tgcggcgcgg cctggaccga aagcgggtgc 11220tgagggacga ggatttcgag gcggacgagc tgacggggat cagccccgcg cgcgcgcacg 11280tggccgcggc caacctggtc acggcgtacg agcagaccgt gaaggaggag agcaacttcc 11340aaaaatcctt caacaaccac gtgcgcacgc tgatcgcgcg cgaggaggtg accctgggcc 11400tgatgcacct gtgggacctg ctggaggcca tcgtgcagaa ccccacgagc aagccgctga 11460cggcgcagct gtttctggtg gtgcagcaca gtcgggacaa cgagacgttc agggaggcgc 11520tgctgaatat caccgagccc gagggccgct ggctcctgga cctggtgaac attctgcaga 11580gcatcgtggt gcaggagcgc gggctgccgc tgtccgagaa gctggcggcc atcaacttct 11640cggtgctgag cctgggcaag tactacgcta ggaagatcta caagaccccg tacgtgccca 11700tagacaagga ggtgaagatc gacgggtttt acatgcgcat gaccctgaaa gtgctgaccc 11760tgagcgacga tctgggggtg taccgcaacg acaggatgca ccgcgcggtg agcgccagcc 11820gccggcgcga gctgagcgac caggagctga tgcacagcct gcagcgggcc ctgaccgggg 11880ccgggaccga gggggagagc tactttgaca tgggcgcgga cctgcgctgg cagcctagcc 11940gccgggcctt ggaagctgcc ggcggttccc cctacgtgga ggaggtggac gatgaggagg 12000aggagggcga gtacctggaa gactgatggc gcgaccgtat ttttgctaga tgcagcaaca 12060gccaccgccg cctcctgatc ccgcgatgcg ggcggcgctg cagagccagc cgtccggcat 12120taactcctcg gacgattgga cccaggccat gcaacgcatc atggcgctga cgacccgcaa 12180tcccgaagcc tttagacagc agcctcaggc caaccgactc tcggccatcc tggaggccgt 12240ggtgccctcg cgctcgaacc ccacgcacga gaaggtgctg gccatcgtga acgcgctggt 12300ggagaacaag gccatccgcg gcgacgaggc cgggctggtg tacaacgcgc tgctggagcg 12360cgtggcccgc tacaacagca ccaacgtgca gacgaacctg gaccgcatgg tgaccgacgt 12420gcgcgaggcg gtgtcgcagc gcgagcggtt ccaccgcgag tcgaacctgg gctccatggt 12480ggcgctgaac gccttcctga gcacgcagcc cgccaacgtg ccccggggcc aggaggacta 12540caccaacttc atcagcgcgc tgcggctgat ggtggccgag gtgccccaga gcgaggtgta 12600ccagtcgggg ccggactact tcttccagac cagtcgccag ggcttgcaga ccgtgaacct 12660gagccaggct ttcaagaact tgcagggact gtggggcgtg caggccccgg tcggggaccg 12720cgcgacggtg tcgagcctgc tgacgccgaa ctcgcgcctg ctgctgctgc tggtggcgcc 12780cttcacggac agcggcagcg tgagccgcga ctcgtacctg ggctacctgc ttaacctgta 12840ccgcgaggcc atcgggcagg cgcacgtgga cgagcagacc taccaggaga tcacccacgt 12900gagccgcgcg ctgggccagg aggacccggg caacctggag gccaccctga acttcctgct 12960gaccaaccgg tcgcagaaga tcccgcccca gtacgcgctg agcaccgagg aggagcgcat 13020cctgcgctac gtgcagcaga gcgtggggct gttcctgatg caggaggggg ccacgcccag 13080
cgccgcgctc gacatgaccg cgcgcaacat ggagcccagc atgtacgccc gcaaccgccc 13140gttcatcaat aagctgatgg actacttgca tcgggcggcc gccatgaact cggactactt 13200taccaacgcc atcttgaacc cgcactggct cccgccgccc gggttctaca cgggcgagta 13260cgacatgccc gaccccaacg acgggttcct gtgggacgac gtggacagca gcgtgttctc 13320gccgcgcccc accaccacca ccgtgtggaa gaaagagggc ggggaccggc ggccgtcctc 13380ggcgctgtcc ggtcgcgcgg gtgctgccgc ggcggtgccc gaggccgcca gccccttccc 13440gagcctgccc ttttcgctga acagcgtgcg cagcagcgag ctgggtcggc tgacgcggcc 13500gcgcctgctg ggcgaggagg agtacctgaa cgactccttg cttcggcccg agcgcgagaa 13560gaacttcccc aataacggga tagagagcct ggtggacaag atgagccgct ggaagacgta 13620cgcgcacgag cacagggacg agccccgagc tagcagcagc accggcgcca cccgtagacg 13680ccagcggcac gacaggcagc ggggtctggt gtgggacgat gaggattccg ccgacgacag 13740cagcgtgttg gacttgggtg ggagtggtgg tggtaacccg ttcgctcacc tgcgcccccg 13800tatcgggcgc ctgatgtaag aatctgaaaa aataaaagac ggtactcacc aaggccatgg 13860cgaccagcgt gcgttcttct ctgttgtttg tagtagtatg atgaggcgcg tgtacccgga 13920gggtcctcct ccctcgtacg agagcgtgat gcagcaggcg gtggcggcgg cgatgcagcc 13980cccgctggag gcgccttacg tgcccccgcg gtacctggcg cctacggagg ggcggaacag 14040cattcgttac tcggagctgg cacccttgta cgataccacc cggttgtacc tggtggacaa 14100caagtcggcg gacatcgcct cgctgaacta ccagaacgac cacagcaact tcctgaccac 14160cgtggtgcag aacaacgatt tcacccccac ggaggccagc acccagacca tcaactttga 14220cgagcgctcg cggtggggcg gccagctgaa aaccatcatg cacaccaaca tgcccaacgt 14280gaacgagttc atgtacagca acaagttcaa ggcgcgggtg atggtctcgc gcaagacccc 14340caacggggtc acagtaacag atggtagtca ggacgagctg acctacgagt gggtggagtt 14400tgagctgccc gagggcaact tctcggtgac catgaccatc gatctgatga acaacgccat 14460catcgacaac tacttggcgg tggggcggca gaacggggtg ctggagagcg acatcggcgt 14520gaagttcgac acgcgcaact tccggctggg ctgggacccc gtgaccgagc tggtgatgcc 14580gggcgtgtac accaacgagg ccttccaccc cgacatcgtc ctgctgcccg gctgcggcgt 14640ggacttcacc gagagccgcc tcagcaacct gctgggcatc cgcaagcggc agcccttcca 14700ggagggcttc cagatcctgt acgaggacct ggaggggggc aacatccccg cgctgctgga 14760cgtggacgcc tacgagaaaa gcaaggagga tagcgccgcc gcggcgaccg cagccgtggc 14820caccgcctct accgaggtgc ggggcgataa ttttgctagc gccgcgacac tggcagcggc 14880cgaggcggct gaaaccgaaa gtaagatagt gatccagccg gtggagaagg acagcaagga 14940gaggagctac aacgtgctcg cggacaagaa aaacaccgcc taccgcagct ggtacctggc 15000ctacaactac ggcgaccccg agaagggcgt gcgctcctgg acgctgctca ccacctcgga 15060cgtcacctgc ggcgtggagc aagtctactg gtcgctgccc gacatgatgc aagacccggt 15120caccttccgc tccacgcgtc aagttagcaa ctacccggtg gtgggcgccg agctcctgcc 15180
cgtctactcc aagagcttct tcaacgagca ggccgtctac tcgcagcagc tgcgcgcctt 15240cacctcgctc acgcacgtct tcaaccgctt ccccgagaac cagatcctcg ttcgcccgcc 15300cgcgcccacc attaccaccg tcagtgaaaa cgttcctgct ctcacagatc acgggaccct 15360gccgctgcgc agcagtatcc ggggagtcca gcgcgtgacc gtcactgacg ccagacgccg 15420cacctgcccc tacgtctaca aggccctggg cgtagtcgcg ccgcgcgtcc tctcgagccg 15480caccttctaa aaaatgtcca ttctcatctc gcccagtaat aacaccggtt ggggcctgcg 15540cgcgcccagc aagatgtacg gaggcgctcg ccaacgctcc acgcaacacc ccgtgcgcgt 15600gcgcgggcac ttccgcgctc cctggggcgc cctcaagggc cgcgtgcgct cgcgcaccac 15660cgtcgacgac gtgatcgacc aggtggtggc cgacgcgcgc aactacacgc ccgccgccgc 15720gcccgtctcc accgtggacg ccgtcatcga cagcgtggtg gccgacgcgc gccggtacgc 15780ccgcgccaag agccggcggc ggcgcatcgc ccggcggcac cggagcaccc ccgccatgcg 15840cgcggcgcga gccttgctgc gcagggccag gcgcacggga cgcagggcca tgctcagggc 15900ggccagacgc gcggcctccg gcagcagcag cgccggcagg acccgcagac gcgcggccac 15960ggcggcggcg gcggccatcg ccagcatgtc ccgcccgcgg cgcggcaacg tgtactgggt 16020gcgcgacgcc gccaccggtg tgcgcgtgcc cgtgcgcacc cgcccccctc gcacttgaag 16080atgctgactt cgcgatgttg atgtgtccca gcggcgagga ggatgtccaa gcgcaaattc 16140aaggaagaga tgctccaggt catcgcgcct gagatctacg gcccggcggc ggtgaaggag 16200gaaagaaagc cccgcaaact gaagcgggtc aaaaaggaca aaaaggagga ggaagatgtg 16260gacggactgg tggagtttgt gcgcgagttc gccccccggc ggcgcgtgca gtggcgcggg 16320cggaaagtga aaccggtgct gcgacccggc accacggtgg tcttcacgcc cggcgagcgt 16380tccggctccg cctccaagcg ctcctacgac gaggtgtacg gggacgagga catcctcgag 16440caggcggccg aacgtctggg cgagtttgct tacggcaagc gcagccgccc cgcgcccttg 16500aaagaggagg cggtgtccat cccgctggac cacggcaacc ccacgccgag cctgaagccg 16560gtgaccctgc agcaggtgct gcctggtgcg gcgccgcgcc ggggcttcaa gcgcgagggc 16620ggcgaggatc tgtacccgac catgcagctg atggtgccca agcgccagaa gctggaggac 16680gtgctggagc acatgaaggt ggaccccgag gtgcagcccg aggtcaaggt gcggcccatc 16740aagcaggtgg ccccgggcct gggcgtgcag accgtggaca tcaagatccc cacggagccc 16800atggaaacgc agaccgagcc cgtgaagccc agcaccagca ccatggaggt gcagacggat 16860ccctggatgc cggcaccggc ttccaccacc cgccgaagac gcaagtacgg cgcggccagc 16920ctgctgatgc ccaactacgc gctgcatcct tccatcatcc ccacgccggg ctaccgcggc 16980acgcgcttct accgcggcta caccagcagc cgccgccgca agaccaccac ccgccgccgc 17040cgtcgtcgca cccgccgcag cagcaccgcg acttccgccg ccgccctggt gcggagagtg 17100taccgcagcg ggcgcgagcc tctgaccctg ccgcgcgcgc gctaccaccc gagcatcgcc 17160atttaactac cgcctcctac ttgcagatat ggccctcaca tgccgcctcc gcgtccccat 17220tacgggctac cgaggaagaa agccgcgccg tagaaggctg acggggaacg ggctgcgtcg 17280
ccatcaccac cggcggcggc gcgccatcag caagcggttg gggggaggct tcctgcccgc 17340gctgatgccc atcatcgccg cggcgatcgg ggcgatcccc ggcatagctt ccgtggcggt 17400gcaggcctct cagcgccact gagacacagc ttggaaaatt tgtaataaaa aatggactga 17460cgctcctggt cctgtgatgt gtgtttttag atggaagaca tcaatttttc gtccctggca 17520ccgcgacacg gcacgcggcc gtttatgggc acctggagcg acatcggcaa cagccaactg 17580aacgggggcg ccttcaattg gagcagtctc tggagcgggc ttaagaattt cgggtccacg 17640ctcaaaacct atggcaacaa ggcgtggaac agcagcacag ggcaggcgct gagggaaaag 17700ctgaaagagc agaacttcca gcagaaggtg gtcgatggcc tggcctcggg catcaacggg 17760gtggtggacc tggccaacca ggccgtgcag aaacagatca acagccgcct ggacgcggtc 17820ccgcccgcgg ggtccgtgga gatgccccag gtggaggagg agctgcctcc cctggacaag 17880cgcggcgaca agcgaccgcg tcccgacgcg gaggagacgc tgctgacgca cacggacgag 17940ccgcccccgt acgaggaggc ggtgaaactg ggtctgccca ccacgcggcc cgtggcgcct 18000ctggccaccg gggtgctgaa acccagcagc agcagcagcc agcccgcgac cctggacttg 18060cctccgcctg cttcccgccc ctccacagtg gctaagcccc tgccgccggt ggccgtcgcg 18120tcgcgcgccc cccgaggccg cccccaggcg aactggcaga gcactctgaa cagcatcgtg 18180ggtctgggag tgcagagtgt gaagcgccgc cgctgctatt aaaagacact gtagcgctta 18240acttgcttgt ctgtgtgtat atgtatgtcc gccgaccaga aggaggagga agaggcgcgt 18300cgccgagttg caagatggcc accccatcga tgctgcccca gtgggcgtac atgcacatcg 18360ccggacagga cgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18420acacctactt cagtctgggg aacaagttta ggaaccccac ggtggcgccc acgcacgatg 18480tgaccaccga ccgcagccag cggctgacgc tgcgcttcgt gcccgtggac cgcgaggaca 18540acacctactc gtacaaagtg cgctacacgc tggccgtggg cgacaaccgc gtgctggaca 18600tggccagcac ctactttgac atccgcggcg tgctggatcg gggccctagc ttcaaaccct 18660actccggcac cgcttacaac agcctggctc ccaagggagc gcccaacact tgccagtgga 18720catataaagc tgatggtgat actggtacag aaaaaaccta tacatatgga aatgcgcctg 18780tgcaaggcat tagtattaca aaagatggta ttcaacttgg aactgacact gatgatcagc 18840ccatttatgc agataaaact tatcaaccag agcctcaagt gggtgatgct gaatggcatg 18900acatcactgg tactgatgaa aaatatggag gcagagctct caagcctgac accaaaatga 18960agccctgcta tggttctttt gccaagccta ccaataaaga aggaggtcag gcaaatgtga 19020aaaccgaaac aggcggtacc aaagaatatg acattgacat ggcattcttc gataatcgaa 19080gtgcagctgc ggctggcctg gccccagaaa ttgttttgta tactgagaat gtggatctgg 19140aaactccaga tactcatatt gtatacaagg cgggcacaga tgacagcagc tcttctatca 19200atttgggtca gcagtccatg cccaacagac ccaactacat tggctttaga gacaacttta 19260tcgggctcat gtactacaac agcactggca acatgggcgt gctggctggt caggcctccc 19320agctgaatgc tgtggtggac ttgcaggaca gaaacactga actgtcctac cagctcttgc 19380
ttgactctct gggcgacaga accaggtatt tcagtatgtg gaatcaggcg gtggacagct 19440atgaccccga tgtgcgcatt attgaaaatc acggtgtgga ggatgaactc cctaactatt 19500gcttccccct ggatgctgtg ggtagaactg atacttacca gggaattaag gccaatggtg 19560ctgatcaaac cacctggacc aaagatgata ctgttaatga tgctaatgaa ttgggcaagg 19620gcaatccttt cgccatggag atcaacatcc aggccaacct gtggcggaac ttcctctacg 19680cgaacgtggc gctgtacctg cccgactcct acaagtacac gccggccaac atcacgctgc 19740cgaccaacac caacacctac gattacatga acggccgcgt ggtggcgccc tcgctggtgg 19800acgcctacat caacatcggg gcgcgctggt cgctggaccc catggacaac gtcaacccct 19860tcaaccacca ccgcaacgcg ggcctgcgct accgctccat gctcctgggc aacgggcgct 19920acgtgccctt ccacatccag gtgccccaaa agttcttcgc catcaagagc ctcctgctcc 19980tgcccgggtc ctacacctac gagtggaact tccgcaagga cgtcaacatg atcctgcaga 20040gctccctcgg caacgacctg cgcacggacg gggcctccat cgccttcacc agcatcaacc 20100tctacgccac cttcttcccc atggcgcaca acaccgcctc cacgctcgag gccatgctgc 20160gcaacgacac caacgaccag tccttcaacg actacctctc ggcggccaac atgctctacc 20220ccatcccggc caacgccacc aacgtgccca tctccatccc ctcgcgcaac tgggccgcct 20280tccgcggatg gtccttcacg cgcctcaaga cccgcgagac gccctcgctc ggctccgggt 20340tcgaccccta cttcgtctac tcgggctcca tcccctacct cgacggcacc ttctacctca 20400accacacctt caagaaggtc tccatcacct tcgactcctc cgtcagctgg cccggcaacg 20460accgcctcct gacgcccaac gagttcgaaa tcaagcgcac cgtcgacgga gaggggtaca 20520acgtggccca gtgcaacatg accaaggact ggttcctggt ccagatgctg gcccactaca 20580acatcggcta ccagggcttc tacgtgcccg agggctacaa ggaccgcatg tactccttct 20640tccgcaactt ccagcccatg agccgccagg tcgtggacga ggtcaactac aaggactacc 20700aggccgtcac cctggcctac cagcacaaca actcgggctt cgtcggctac ctcgcgccca 20760ccatgcgcca gggacagccc taccccgcca actaccccta cccgctcatc ggcaagagcg 20820ccgtcgccag cgtcacccag aaaaagttcc tctgcgaccg ggtcatgtgg cgcatcccct 20880tctccagcaa cttcatgtcc atgggcgcgc tcaccgacct cggccagaac atgctctacg 20940ccaactccgc ccacgcgcta gacatgaatt tcgaagtcga ccccatggat gagtccaccc 21000ttctctatgt tgtcttcgaa gtcttcgacg tcgtccgagt gcaccagccc caccgcggcg 21060tcatcgaggc cgtctacctg cgcacgccct tctcggccgg caacgccacc acctaagccc 21120cgctcttgct tcttgcaaga tgacggcctg tgcgggctcc ggcgagcagg agctcagggc 21180catcctccgc gacctgggct gcgggccctg cttcctgggc accttcgaca agcgcttccc 21240gggattcatg gccccgcaca agctggcctg cgccatcgtc aacacggccg gccgcgagac 21300cgggggcgag cactggctgg ccttcgcctg gaacccgcgc tcccacacct gctacctctt 21360cgaccccttc gggttctcgg acgagcgcct caagcagatc taccagttcg agtacgaggg 21420cctgctgcgc cgcagcgccc tggccaccga ggaccgctgc gtcaccctgg aaaagtccac 21480
ccagaccgtg cagggtccgc gctcggccgc ctgcgggctc ttctgctgca tgttcctgca 21540cgccttcgtg cactggcccg accgccccat ggacaagaac cccaccatga acttgctgac 21600gggggtgccc aacggcatgc tccagtcgcc ccaggtggaa cccaccctgc gccgcaacca 21660ggaggcgctc taccgcttcc tcaacgccca ctccgcctac tttcgctccc accgcgcgcg 21720catcgagaag gccaccgcct tcgaccgcat gaatcaagac atgtaaaccg tgtgtgtatg 21780tgaatgcttt attcataata aacagcacat gtttatgcca ccttttctga ggctctgact 21840ttatttagaa atcgaagggg ttctgccggc tctcggcgtg ccccgcgggc agggatacgt 21900tgcggaactg gtacttgggc agccacttga actcggggat cagcagcttc ggcacgggga 21960ggtcggggaa cgagtcgctc cacagcttgc gcgtgagttg cagggcgccc agcaggtcgg 22020gcgcggagat cttgaaatcg cagttgggac ccgcgttctg cgcgcgggag ttgcggtaca 22080cggggttgca gcactggaac accatcaggg ccgggtgctt cacgctcgcc agcaccgtcg 22140cgtcggtgat gccctccacg tccagatcct cggcgttggc catcccgaag ggggtcatct 22200tgcaggtctg ccgccccatg ctgggcacgc agccgggctt gtggttgcaa tcgcagtgca 22260gggggatcag catcatctgg gcctgctcgg agctcatgcc cgggtacatg gccttcatga 22320aagcctccag ctggcggaag gcctgctgcg ccttgccgcc ctcggtgaag aagaccccgc 22380aggacttgct agagaactgg ttggtggcgc agccggcgtc gtgcacgcag cagcgcgcgt 22440cgttgttggc cagctgcacc acgctgcgcc cccagcggtt ctgggtgatc ttggcccggt 22500cggggttctc cttcagcgcg cgctgcccgt tctcgctcgc cacatccatc tcgatcgtgt 22560gctccttctg gatcatcacg gtcccgtgca ggcatcgcag cttgccctcg gcctcggtgc 22620acccgtgcag ccacagcgcg cagccggtgc actcccagtt cttgtgggcg atctgggagt 22680gcgagtgcac gaagccctgc aggaagcggc ccatcatcgt ggtcagggtc ttgttgctgg 22740tgaaggtcag cgggatgccg cggtgctcct cgttcacata caggtggcag atgcggcggt 22800acacctcgcc ctgctcgggc atcagctgga aggcggactt caggtcgctc tccacgcggt 22860accggtccat cagcagcgtc atgacttcca tgcccttctc ccaggccgag acgatcggca 22920ggctcagggg gttcttcacc gccgttgtca tcttagtcgc cgccgctgag gtcagggggt 22980cgttctcgtc cagggtctca aacactcgct tgccgtcctt ctcggtgatg cgcacggggg 23040gaaagctgaa gcccacggcc gccagctcct cctcggcctg cctttcgtcc tcgctgtcct 23100ggctgatgtc ttgcaaaggc acatgcttgg tcttgcgggg tttctttttg ggcggcagag 23160gcggcggcgg agacgtgctg ggcgagcgcg agttctcgct caccacgact atttcttctt 23220cttggccgtc gtccgagacc acgcggcggt aggcatgcct cttctggggc agaggcggag 23280gcgacgggct ctcgcggttc ggcgggcggc tggcagagcc ccttccgcgt tcgggggtgc 23340gctcctggcg gcgctgctct gactgacttc ctccgcggcc ggccattgtg ttctcctagg 23400gagcaacaag catggagact cagccatcgt cgccaacatc gccatctgcc cccgccgccg 23460ccgacgagaa ccagcagcag aatgaaagct taaccgcccc gccgcccagc cccacctccg 23520acgccgccgc ggccccagac atgcaagaga tggaggaatc catcgagatt gacctgggct 23580
acgtgacgcc cgcggagcac gaggaggagc tggcagcgcg cttttcagcc ccggaagaga 23640accaccaaga gcagccagag caggaagcag agagcgagca gcagcaggct gggctcgagc 23700atggcgacta cctgagcggg gcagaggacg tgctcatcaa gcatctggcc cgccaatgca 23760tcatcgtcaa ggacgcgctg ctcgaccgcg ccgaggtgcc cctcagcgtg gcggagctca 23820gccgcgccta cgagcgcaac ctcttctcgc cgcgcgtgcc ccccaagcgc cagcccaacg 23880gcacctgcga gcccaacccg cgcctcaact tctacccggt cttcgcggtg cccgaggccc 23940tggccaccta ccacctcttt ttcaagaacc aaaggatccc cgtctcctgc cgcgccaacc 24000gcacccgcgc cgacgccctg ctcaacctgg gtcccggcgc ccgcctacct gatatcgcct 24060ccttggaaga ggttcccaag atcttcgagg gtctgggcag cgacgagact cgggccgcga 24120acgctctgca aggaagcgga gaggagcatg agcaccacag cgccctggtg gagttggaag 24180gcgacaacgc gcgcctggcg gtgctcaagc gcacggtcga gctgacccac ttcgcctacc 24240cggcgctcaa cctgcccccc aaggtcatga gcgccgtcat ggaccaggtg ctcatcaagc 24300gcgcctcgcc cctctcggat gaggacatgc aggaccccga gagctcggac gagggcaagc 24360ccgtggtcag cgacgagcag ctggcgcgct ggctgggagc gagtagcacc ccccagagct 24420tggaagagcg gcgcaagctc atgatggccg tggtcctggt gaccgtggag ctggagtgtc 24480tgcgccgctt cttcgccgac gcagagaccc tgcgcaaggt cgaggagaac ctgcactacc 24540tcttcaggca cgggtttgtg cgccaggcct gcaagatctc caacgtggag ctgaccaacc 24600tggtctccta catgggcatc ctgcacgaga accgcctggg gcagaacgtg ctgcacacca 24660ccctgcgcgg ggaggcccgc cgcgactaca tccgcgactg cgtctacctg tacctctgcc 24720acacctggca gacgggcatg ggcgtgtggc agcagtgcct ggaggagcag aacctgaaag 24780agctctgcaa gctcctgcag aagaacctga aggccctgtg gaccgggttc gacgagcgca 24840ccaccgcctc ggacctggcc gacctcatct tccccgagcg cctgcggctg acgctgcgca 24900acggactgcc cgactttatg agtcaaagca tgttgcaaaa ctttcgctct ttcatcctcg 24960aacgctccgg gatcctgccc gccacctgct ccgcgctgcc ctcggacttc gtgccgctga 25020ccttccgcga gtgccccccg ccgctctgga gccactgcta cctgctgcgc ctggccaact 25080acctggccta ccactcggac gtgatcgagg acgtcagcgg cgagggtctg ctcgagtgcc 25140actgccgctg caacctctgc acgccgcacc gctccctggc ctgcaacccc cagctgctga 25200gcgagaccca gatcatcggc accttcgagt tgcaaggccc cggcgagggc aaggggggtc 25260tgaaactcac cccggggctg tggacctcgg cctacttgcg caagttcgtg cccgaggact 25320accatccctt cgagatcagg ttctacgagg accaatccca gccgcccaag gccgaactgt 25380cggcctgcgt catcacccag ggggccatcc tggcccaatt gcaagccatc cagaaatccc 25440gccaagaatt tctgctgaaa aagggccacg gggtctacct ggacccccag accggagagg 25500agctcaaccc cagcttcccc caggatgccc cgaggaagca gcaagaagct gaaagtggag 25560ctgccgccgc cggaggattt ggaggaagac tgggagagca gtcaggcaga ggaggaggag 25620atggaagact gggacagcac tcaggcagag gaggacagcc tgcaagacag tctggaagac 25680
gaggtggagg aggaggcaga ggaagaagca gccgccgcca gaccgtcgtc ctcggcggag 25740aaagcaagca gcacggatac catctccgct ccgggtcggg gtcgcggcga ccgggcccac 25800agtaggtggg acgagaccgg gcgcttcccg aaccccacca cccagaccgg taagaaggag 25860cggcagggat acaagtcctg gcgggggcac aaaaacgcca tcgtctcctg cttgcaagcc 25920tgcgggggca acatctcctt cacccgccgc tacctgctct tccaccgcgg ggtgaacttc 25980ccccgcaaca tcttgcatta ctaccgtcac ctccacagcc cctactactg tttccaagaa 26040gaggcagaaa cccagcagca gcagaaaacc agcggcagca gcagctagaa aatccacagc 26100ggcggcaggt ggactgagga tcgcagcgaa cgagccggcg cagacccggg agctgaggaa 26160ccggatcttt cccaccctct atgccatctt ccagcagagt cgggggcagg agcaggaact 26220gaaagtcaag aaccgttctc tgcgctcgct cacccgcagt tgtctgtatc acaagagcga 26280agaccaactt cagcgcactc tcgaggacgc cgaggctctc ttcaacaagt actgcgcgct 26340cactcttaaa gagtagcccg cgcccgccca cacacggaaa aaggcgggaa ttacgtcacc 26400acctgcgccc ttcgcccgac catcatcatg agcaaagaga ttcccacgcc ttacatgtgg 26460agctaccagc cccagatggg cctggccgcc ggcgccgccc aggactactc cacccgcatg 26520aactggctca gcgccgggcc cgcgatgatc tcacgggtga atgacatccg cgcccgccga 26580aaccagatac tcctagaaca gtcagcgatc accgccacgc cccgccatca ccttaatccg 26640cgtaattggc ccgccgccct ggtgtaccag gaaattcccc agcccacgac cgtactactt 26700ccgcgagacg cccaggccga agtccagctg actaactcag gtgtccagct ggccggcggc 26760gccgccctgt gtcgtcaccg ccccgctcag ggtataaagc ggctggtgat ccgaggcaga 26820ggcacacagc tcaacgacga ggtggtgagc tcttcgctgg gtctgcgacc tgacggagtc 26880ttccaactcg ccggatcggg gagatcttcc ttcacgcctc gtcaggccgt cctgactttg 26940gagagttcgt cctcgcagcc ccgctcgggt ggcatcggca ctctccagtt cgtggaggag 27000ttcactccct cggtctactt caaccccttc tccggctccc ccggccacta cccggacgag 27060ttcatcccga acttcgacgc catcagcgag tcggtggacg gctacgattg aatgtcccat 27120ggtggcgcag ctgacctagc tcggcttcga cacctggacc actgtcgcct ctcctacgag 27180ctcctgcagc agcgccagaa gttcacctgc ctggtcggag tcaaccccat cgtcatcacc 27240cagcagtcgg gcgataccaa ggggtgcatc cactgctcct gcgactcccc cgactgcgtc 27300cacactctga tcaagaccct ctgcggcctc cgcgacctcc tccccatgaa ctaatcaccc 27360ccttatccag tgaaataaag atcatattga tgatttgagt ttaataaaaa taaagaatca 27420cttacttgaa atctgatacc aggtctctgt ccatgttttc tgccaacacc acttcactcc 27480cctcttccca gctctggtac tgcaggcccc ggcgggctgc aaacttcctc cacaccctga 27540aggggatgtc aaattcctcc tgtccctcaa tcttcatttt atcttctatc agatgtccaa 27600aaagcgcgtc cgggtggatg atgacttcga ccccgtctac ccctacgatg cagacaacgc 27660accgaccgtg cccttcatca accccccctt cgtctcttca gatggattcc aagagaagcc 27720cctgggggtg ctgtccctgc gtctggccga tcccgtcacc accaagaacg gggaaatcac 27780
cctcaagctg ggagatgggg tggacctcga ctcctcggga aaactcatct ccaacacggc 27840caccaaggcc gccgcccctc tcagtttttc caacaacacc atttccctta acatggatac 27900ccctttttac aacaacaatg gaaagttagg catgaaagtc actgctccac tgaagatact 27960agacacagac ttgctaaaaa cacttgttgt agcttatgga caaggtttag gaacaaacac 28020cactggtgcc cttgttgccc aactagcatc cccacttgct tttgatagca atagcaaaat 28080tgcccttaat ttaggcaatg gaccattgaa agtggatgca aatagactga acatcaattg 28140caatagagga ctctatgtta ctaccacaaa agatgcactg gaagccaata taagttgggc 28200taatgctatg acatttatag gaaatgccat gggtgtcaat attgatacac aaaaaggctt 28260gcaatttggc accactagta ccgtcgcaga tgttaaaaac gcttacccca tacaaatcaa 28320acttggagct ggtctcacat ttgacagcac aggtgcaatt gttgcatgga acaaagatga 28380tgacaagctt acactatgga ccacagccga cccctctcca aattgtcaca tatattctga 28440aaaggatgct aagcttacac tttgcttgac aaagtgtggc agtcagattc tgggcactgt 28500ttccctcata gctgttgata ctggcagttt aaatcccata acaggaacag taaccactgc 28560tcttgtctca cttaaattcg atgcaaatgg agttttgcaa agcagctcaa cactagactc 28620agactattgg aatttcagac agggagatgt tacacctgct gaagcctata ctaatgctat 28680aggtttcatg cccaatctaa aagcataccc taaaaacaca agtggagctg caaaaagtca 28740cattgttggg aaagtgtacc tacatgggga tacaggcaaa ccactggacc tcattattac 28800tttcaatgaa acaagtgatg aatcttgcac ttactgtatt aactttcaat ggcagtgggg 28860ggctgatcaa tataaaaatg aaacacttgc cgtcagttca ttcacctttt cctatattgc 28920taaagaataa accccactct gtaccccatc tctgtctatg gaaaaaactc tgaaacacaa 28980aataaaataa agttcaagtg ttttattgat tcaacagttt tacaggattc gagcagttat 29040ttttcctcca ccctcccagg acatggaata caccaccctc tccccccgca cagccttgaa 29100catctgaatg ccattggtga tggacatgct tttggtctcc acgttccaca cagtttcaga 29160gcgagccagt ctcgggtcgg tcagggagat gaaaccctcc gggcactccc gcatctgcac 29220ctcacagctc aacagctgag gattgtcctc ggtggtcggg atcacggtta tctggaagaa 29280gcagaagagc ggcggtggga atcatagtcc gcgaacggga tcggccggtg gtgtcgcatc 29340aggccccgca gcagtcgctg tcgccgccgc tccgtcaagc tgctgctcag ggggtccggg 29400tccagggact ccctcagcat gatgcccacg gccctcagca tcagtcgtct ggtgcggcgg 29460gcgcagcagc gcatgcggat ctcgctcagg tcgctgcagt acgtgcaaca caggaccacc 29520aggttgttca acagtccata gttcaacacg ctccagccga aactcatcgc gggaaggatg 29580ctacccacgt ggccgtcgta ccagatcctc aggtaaatca agtggcgccc cctccagaac 29640acgctgccca tgtacatgat ctccttgggc atgtggcggt tcaccacctc ccggtaccac 29700atcaccctct ggttgaacat gcagccccgg atgatcctgc ggaaccacag ggccagcacc 29760gccccgcccg ccatgcagcg aagagacccc gggtcccgac aatggcaatg gaggacccac 29820cgctcgtacc cgtggatcat ctgggagctg aacaagtcta tgttggcaca gcacaggcat 29880
atgctcatgc atctcttcag cactctcagc tcctcggggg tcaaaaccat atcccagggc 29940acggggaact cttgcaggac agcgaacccc gcagaacagg gcaatcctcg cacataactt 30000acattgtgca tggacagggt atcgcaatca ggcagcaccg ggtgatcctc caccagagaa 30060gcgcgggtct cggtctcctc acagcgtggt aagggggccg gccgatacgg gtgatggcgg 30120gacgcggctg atcgtgttcg cgaccgtgtt atgatgcagt tgctttcgga cattttcgta 30180cttgctgtag cagaacctgg tccgggcgct gcacaccgat cgccggcggc ggtcccggcg 30240cttggaacgc tcggtgttga agttgtaaaa cagccactct ctcagaccgt gcagcagatc 30300tagggcctca ggagtgatga agatcccatc atgcctgatg gctctaatca catcgaccac 30360cgtggaatgg gccagaccca gccagatgat gcaattttgt tgggtttcgg tgacggcggg 30420ggagggaaga acaggaagaa ccatgattaa cttttaatcc aaacggtctc ggagcacttc 30480aaaatgaaga tcgcggagat ggcacctctc gcccccgctg tgttggtgga aaataacagc 30540caggtcaaag gtgatacggt tctcgagatg ttccacggtg gcttccagca aagcctccac 30600gcgcacatcc agaaacaaga caatagcgaa agcgggaggg ttctctaatt cctcaatcat 30660catgttacac tcctgcacca tccccagata attttcattt ttccagcctt gaatgattcg 30720aactagttcc tgaggtaaat ccaagccagc catgataaag agctcgcgca gagcgccctc 30780caccggcatt cttaagcaca ccctcataat tccaagatat tctgctcctg gttcacctgc 30840agcagattga caagcggaat atcaaaatct ctgccgcgat ccctaagctc ctccctcagc 30900aataactgta agtactcttt catatcctct ccgaaatttt tagccatagg accaccagga 30960ataagattag ggcaagccac agtacagata aaccgaagtc ctccccagtg agcattgcca 31020aatgcaagac tgctataagc atgctggcta gacccggtga tatcttccag ataactggac 31080agaaaatcgc ccaggcaatt tttaagaaaa tcaacaaaag aaaaatcctc caggtgcacg 31140tttagagcct cgggaacaac gatggagtaa atgcaagcgg tgcgttccag catggttagt 31200tagctgatct gtagaaaaaa acaaaaatga acattaaacc atgctagcct ggcgaacagg 31260tgggtaaatc gttctctcca gcaccaggca ggccacgggg tctccggcac gaccctcgta 31320aaaattgtcg ctatgattga aaaccatcac agagagacgt tcccggtggc cggcgtgaat 31380gattcgacaa gatgaataca cccccggaac attggcgtcc gcgagtgaaa aaaagcgccc 31440aaggaagcaa taaggcacta caatgctcag tctcaagtcc agcaaagcga tgccatgcgg 31500atgaagcaca aaattctcag gtgcgtacaa aatgtaatta ctcccctcct gcacaggcag 31560caaagccccc gatccctcca ggtacacata caaagcctca gcgtccatag cttaccgagc 31620agcagcacac aacaggcgca agagtcagag aaaggctgag ctctaacctg tccacccgct 31680ctctgctcaa tatatagccc agatctacac tgacgtaaag gccaaagtct aaaaataccc 31740gccaaataat cacacacgcc cagcacacgc ccagaaaccg gtgacacact caaaaaaata 31800cgcgcacttc ctcaaacgcc caaactgccg tcatttccgg gttcccacgc tacgtcatca 31860aaattcgact ttcaaattcc gtcgaccgtt aaaaacgtcg cccgccccgc ccctaacggt 31920cgccgctccc gcagccaatc accgccccgc atccccaaat tcaaatacct catttgcata 31980
ttaacgcgca ccaaaagttt gaggtatatt attgatgatg 3202021062111737212DNA213黑猩猩腺病毒-ChAd 20纖維4006atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60agcggccctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120gaaagtcccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgctggcaa cctcacctct 240caagatatca ccaccgctag ccctcccctc aaaaaaacca agaccaacct cagcctagaa 300acctcatccc ccctaactgt gagcacctca ggcgccctca ccgtagcagc cgccgctccc 360ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtacaggat 420gcaaaactca ccctggccac caaaggcccc ctgaccgtgt ctgaaggcaa actggccttg 480caaacatcgg ccccgctgac ggccgctgac agcagcaccc tcacagtcag tgccacacca 540ccccttagca caagcaatgg cagcttgggt attgacatgc aagcccccat ttacaccacc 600aatggaaaac taggacttaa ctttggcgct cccctgcatg tggtagacag cctaaatgca 660ctgactgtag ttactggcca aggtcttacg ataaacggaa cagccctaca aactagagtc 720tcaggtgccc tcaactatga cacatcagga aacctagaat tgagagctgc agggggtatg 780cgagttgatg caaatggtca acttatcctt gatgtagctt acccatttga tgcacaaaac 840aatctcagcc ttaggcttgg acagggaccc ctgtttgtta actctgccca caacttggat 900gttaactaca acagaggcct ctacctgttc acatctggaa ataccaaaaa gctagaagtt 960aatatcaaaa cagccaaggg tctcatttat gatgacactg ctatagcaat caatgcgggt 1020gatgggctac agtttgactc aggctcagat acaaatccat taaaaactaa acttggatta 1080ggactggatt atgactccag cagagccata attgctaaac tgggaactgg cctaagcttt 1140gacaacacag gtgccatcac agtaggcaac aaaaatgatg acaagctcac cttgtggacc 1200acaccagacc catctcctaa ctgtagaatc tattcagaga aagatgctaa attcacactt 1260gttttgacta aatgcggcag tcaggtgttg gccagcgttt ctgttttatc tgtaaaaggt 1320agccttgcgc ccatcagtgg cacagtaact agtgctcaga ttgtcctcag atttgatgaa 1380aatggagttc tactaagcaa ttcttccctt gaccctcaat actggaacta cagaaaaggt 1440gaccttacag agggcactgc atataccaac gcagtgggat ttatgcccaa cctcacagca 1500tacccaaaaa cacagagcca aactgctaaa agcaacattg taagtcaggt ttacttgaat 1560ggggacaaat ccaaacccat gaccctcacc attaccctca atggaactaa tgaaacagga 1620
gatgccacag taagcactta ctccatgtca ttctcatgga actggaatgg aagtaattac 1680attaatgaaa cgttccaaac caactccttc accttctcct acatcgccca agaataa173721072111278212DNA213黑猩猩腺病毒-ChAd 4纖維4007atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgatt cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720aaagaagacg ataaactcac tttgtggaca acacctgatc catcaccaaa ctgtcaaata 780ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260tacatcgccc aagaatga 127821082111335212DNA
213黑猩猩腺病毒-ChAd 5纖維4008atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgct gtccctgcgt ctggccgatc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agatggggtg gacctcgacg actcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc tttttcactc 720caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcaaatccta 900ggcactgtct ccctattagc agtcagtggc agcttggctc ctatcacagg ggctgttaga 960actgcacttg tatcactcaa attcaatgct aatggagccc ttttggacaa atcaactctg 1020aacaaagaat actggaacta cagacaagga gatctaattc caggtacacc atatacacat 1080gctgtgggtt tcatgcctaa caaaaaagcc taccctaaaa acacaactgc agcttccaag 1140agccacattg tgggtgatgt gtatttagat ggagatgcag ataaaccttt atctcttatc 1200atcactttca atgaaactga tgatgaaacc tgtgattact gcatcaactt tcaatggaaa 1260tggggagctg atcaatataa ggataagaca ctcgcaacca gttcattcac cttctcatac 1320atcgcccaag aataa 133521092111338212DNA213黑猩猩腺病毒-ChAd 7纖維4009atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggataccc ctttttacaa caataatgga aagttaggca tgaaagtcac tgctccactg 360aagatactcg acacagactt gctaaaaaca cttgttgtag cttatggaca aggtttagga 420acaaacacca ctggtgccct tgttgcccaa ctagcagccc cacttgcttt tgatagcaat 480agcaaaattg cccttaattt aggcaatgga ccattgaaag tggatgcaaa tagactgaac 540atcaattgca atagaggact ctatgttact accacaaaag atgcactgga aaccaacata 600agttgggcta atgctatgac atttatagga aatgccatgg gtgtcaatat tgatacacaa 660aaaggcttgc aatttggcac cactagtacc gtcgcagatg ttaaaaacgc ttaccccata 720caagtcaaac tgggagctgg tctcacattt gacagcacag gtgcaattgt cgcttggaac 780aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840tattctgaca aggatgctaa gcttacactc tgcttgacaa agtgtggcag tcagatactg 900ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggacaagta 960accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaaac cagttcaaca 1020ttggacaaag aatattggaa ttttagaaaa ggagatgtga cacctgctga gccatatact 1080aatgctatag gtttcatgcc caatctaaag gcatacccta aaaacacaag tggagctgca 1140aaaagtcaca ttgttgggaa agtgtaccta catggggata cagacaaacc actggacctg 1200attattactt tcaatgaaac aagtgatgaa tcttgcactt actgtattaa ctttcaatgg 1260aaatgggata gtactaagta cacaggtgaa acacttgcta caagctcctt caccttctcc 1320tacattgccc aagaatga 1338210102111278212DNA213黑猩猩腺病毒-chAd 9纖維40010atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc tgcccctctc agtttttcca acaacaccat ttcccttaac 300atggatcacc ccttttacac taaagatgga aaattagcct tacaagtttc tccaccatta 360
aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600aatgggttag agtttggaag cagtagtaca gaaacaggtg tcgatgatgc ttacccaatc 660caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720aaagaagacg ataaactcac tttgtggaca acacctgatc catcaccaaa ctgtcaaata 780ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840gccactgtgt cagtcttagt tgtaggaagt ggagacctaa accccattac tggcaccgta 900agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatgcc 1020aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200acctggacta atggaagcta tgttggagca acatttggag ctaactctta taccttctcc 1260tacatcgccc aagaatga 1278210112111278212DNA213黑猩猩腺病毒-ChAd 10纖維40011atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720
aaagaagacg ataaactcac tttgtggaca acacctgatc catcgccaaa ctgtcaaata 780ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260tacatcgccc aagaatga 1278210122111737212DNA213黑猩猩腺病毒-ChAd 11纖維40012atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgttccc 360ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actagccttg 480cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcacaatcag cgccacaccg 540ccccttagca caagcaatgg cagcttgggt attgacatgc aagcccccat ttacactact 600aacggaaaac tgggacttaa ctttggtgct cccctgcatg tggtagacag cctaaatgca 660ctgactgtag tgactggcca aggtcttacg ataaacggta cagccctaca aactagagtc 720tcaggtgccc tcaactatga ctcatcagga aacctagaat tgagagctgc agggggtatg 780cgagttgatg caaatggcaa acttatcctt gacgtagctt acccatttga tgctcaaaac 840aacctcagcc ttagacttgg acagggaccc ctgtttgtta actctgccca caacttggat 900gttaactaca acagaggcct ctacctgttc acatctggaa ataccaaaaa gctagaagtt 960aatatcaaaa cagccaaagg cctcatttat gatgacactg ctatagcaat caatccaggc 1020gatgggctag agtttggctc aggctcagat acaaatccat taaaaactaa acttggattg 1080
ggactagagt atgactccag cagagccata attgctaagc tgggaaccgg cctaagcttt 1140gacaacacag gtgccatcac agtgggcaac aaaaatgatg acaagcttac cttgtggacc 1200acaccagacc cctctcccaa ctgtagaatt tattcagaaa aagatgctaa atttacacta 1260gttttaacta aatgcggcag tcaggtgttg gccagcgttt ctgttttatc tgtaaaaggc 1320agccttgcgc ccatcagtgg cacagtaact agcgctcaga ttattctcag atttgatgaa 1380aatggagttc tactaagcaa ttcttctctt gacccccaat actggaacta cagaaaaggt 1440gaccttacag agggcactgc atataccaac gcagtgggat ttatgcccaa cctcacagca 1500tacccaaaaa cacagagtca aactgctaaa agcaacattg taagccaggt ttacttgaat 1560ggggacaaat ccaaacccat gatcctcacc attaccctca atggaactaa tgaaacaggg 1620gatgctacag ttagcactta ctccatgtca ttctcatgga attggaatgg aagtaattac 1680attaatgaaa cgttccaaac caactctttc accttctcct acatcgccca agaataa1737210132111632212DNA213黑猩猩腺病毒-ChAd 16纖維40013atgaagcgca ccaaaacgtc tgacaagagc ttcaaccccg tgtaccccta tgacacggaa 60aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgccccc 360ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actggccttg 480cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag cgccacacca 540cccatcagtg taagcagtgg aagtttgggc ttagacatgg aagacccaat gtatactcat 600gatggaaaac tgggaataag aattgggggc ccactgagag tagtagacag cctgcacaca 660ctgactgtag ttaccggaaa tggaatagct gtagataaca atgccctcca aactagagtt 720acgggcgccc tgggttatga cacatcagga aacctacaac tgagagccgc ggggggtatg 780cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa acacagacca caacctagat 900ttgaattgca acagaggtct gaccacaact accaccaaca acacaaaaaa acttgaaact 960aaaattggct caggcttaga ctatgatacc aatggtgctg ttattattaa acttggcact 1020
ggtgtcagct ttgacagcac aggtgcccta agtgtgggaa acactggcga tgataaactg 1080actctgtgga caaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140aagtttactc tagtcctaac taagtgtgga agtcaaatcc tggcttctgt cgccgcccta 1200gcggtgtcag gaaatctggc ttcaataaca ggcaccgttt ccagcgttac catctttctc 1260agatttgatc agaatggagt gcttatggaa aactcctcgc tagacaagca gtactggaac 1320ttcagaaatg gtaattcaac caatgccacc ccctacacca atgcagttgg gtttatgcca 1380aacctcgcag cataccccaa gacacagagc cagactgcaa aaaacaacat tgtaagtcag 1440gtttacttga atggggacaa atccaaaccc atgaccctta ccattaccct caatggaact 1500aatgaatcca gtgaaactag ccaggtgagt cactactcca tgtcatttac gtgggcttgg 1560gagagtgggc aatatgccac cgaaaccttt gccaccaatt cctttacctt ctcttacatt 1620gctgaacaat aa 1632210142111632212DNA213黑猩猩腺病毒-ChAd 17纖維40014atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60agcggccctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120gaaagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180atgcttgccc tgaaaatggg aagtggcctc tccctggacg acgctggcaa ccttacctct 240caagatatta cctccactac ccctcccctc aaaaaaacca agaccaacct cagcctagaa 300acctcatccc ccctaactgt aagcacctca ggcgccctca ccgtagcagc cgccgctccc 360ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctggc agtacaggat 420gcaaaactca ccctggccac caaaggcccc ctgaccgtgt ctgaaggcaa actggccttg 480caaacatcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag ctccactcca 540ccaattagtg taagcagtgg aagtttgggc ttggacatgg aagaccccat gtatactcac 600gatggaaaac tgggaataag aattgggggt ccactaagag tagtagacag cttgcacaca 660ctcactgtag ttaccggaaa tggactaact gtagataaca atgccctcca aactagagtt 720acgggcgccc taggttatga cacatcagga aatctacaac tgagagccgc agggggtatg 780cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa atacagacca caacctggat 900ttaaattgca acagaggtct aaccacaact accaccaaca acacaaaaaa acttgagact 960aaaattagct caggcttaga ctatgacacc aatggtgctg tcattattaa acttggcact 1020
ggtctaagct tcgacaacac aggcgcccta actgtgggaa acactggtga tgataaactg 1080actctgtgga cgaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140aagtttactc tcgtcctaac taagtgtgga agccaaatcc tggcctctgt cgccgcccta 1200gcggtatcag gaaatctggc ttcgataaca ggcaccgttg ccagcgttac catctttctt 1260agatttgatc agaatggagt gcttatggaa aactcctcac tagacaagca gtactggaac 1320ttcagaaatg gcaattcaac taatgctgcc ccctacacca acgcagttgg gttcatgcca 1380aacctcgcag cgtaccccaa aacgcaaagc cagactgcta aaaacaacat tgtaagtcag 1440gtttacttga atggagacaa atccaaaccc atgaccctta ccatcaccct caatggaact 1500aatgaatcca gtgaaactag tcaggtgagt cactactcca tgtcatttac atgggcttgg 1560gaaagcgggc aatatgccac tgaaaccttt gccaccaact ccttcacctt ttcttacatt 1620gctgaacaat aa 1632210152111632212DNA213黑猩猩腺病毒-ChAd 19纖維40015atgaagcgca ccaaaacgtc tgacaagagc ttcaaccccg tgtaccccta tgacacggaa 60aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgccccc 360ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actggccttg 480cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag cgccacacca 540cccatcagtg taagcagtgg aagtttgggc ttagacatgg aagacccaat gtatactcat 600gatggaaaac tgggaataag aattgggggc ccactgagag tagtagacag cctgcacaca 660ctgactgtag ttaccggaaa tggaatagct gtagataaca atgccctcca aactagagtt 720acgggcgccc tgggttatga cacatcagga aacctacaac tgagagccgc ggggggtatg 780cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa acacagacca caacctagat 900ttgaattgca acagaggtct gaccacaact accaccaaca acacaaaaaa acttgaaact 960aaaattggct caggcttaga ctatgatacc aatggtgctg ttattattaa acttggcact 1020
ggtgtcagct ttgacagcac aggtgcccta agtgtgggaa acactggcga tgataaactg 1080actctgtgga caaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140aagtttactc tagtcctaac taagtgtgga agtcaaatcc tggcttctgt cgccgcccta 1200gcggtgtcag gaaatctggc ttcaataaca ggcaccgttt ccagcgttac catctttctc 1260agatttgatc agaatggagt gcttatggaa aactcctcgc tagacaagca gtactggaac 1320ttcagaaatg gtaattcaac caatgccacc ccctacacca atgcagttgg gtttatgcca 1380aacctcgcag cataccccaa gacacagagc cagactgcaa aaaacaacat tgtaagtcag 1440gtttacttga atggggacaa atccaaaccc atgaccctta ccattaccct caatggaact 1500aatgaatcca gtgaaactag ccaggtgagt cactactcca tgtcatttac gtgggcttgg 1560gagagtgggc aatatgccac cgaaaccttt gccaccaatt cctttacctt ctcttacatt 1620gctgaacaat aa 1632210162112865212DNA213黑猩猩腺病毒-ChAd 20六鄰體40016atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360tacaactccc tggcccccaa gggcgctccc aacccatgcg agtgggatga ggctgctact 420gcccttgaca ttgatttgaa cgcagaagac gatgaagaaa gcgacgaagc tcaaggggaa 480gcagatcagc agaaaactca tgtatttggc caggcgccct actccggaca gaacattaca 540aaagaaggca tacagatagg catagatgct gccagtcaag cccagacacc tgtatatgcc 600gataaaacat tccaaccaga acctcaagtt ggagaatcac agtggaatga gacagagatt 660agttatggag cgggacgggt gcttaaaaaa accactctca tgaaaccttg ctatgggtcg 720tatgcaaggc ctactaatga gaacggaggt cagggcatcc tcttggaaca agatggaaag 780aaagaaagtc aagtggaaat gcaatttttc tctactactc aggcagccgc gggtaattca 840gataatccta ccccaaaggt tgttttgtac agcgaggatg ttaacctgga aacaccagat 900acacacattt catacatgcc caccaacaac gagacaaatt caagagagct tttgggacaa 960caggccatgc ccaacaggcc taattacatt ggcttcagag acaactttat cggtctcatg 1020
tattacaaca gcactggcaa catgggagtg cttgcaggtc aggcctctca gttgaacgca 1080gtggtggact tgcaagacag aaacacagaa ctgtcatacc agctcttgct tgattccatg 1140ggtgacagaa ccagatactt ttccatgtgg aatcaggcag tggacagtta tgacccagat 1200gtcagaatta ttgaaaatca tggaactgaa gacgagctcc ccaactattg tttccctctg 1260ggcggcgtaa tcaatacgga aactttcaca aaagtaaaac ctaaagctgc acaggacgct 1320cagtgggaaa aagattcaga attttcagat aaaaatgaaa taagggtggg aaacaacttc 1380gccatggaaa ttaacctcaa tgccaatctg tggaggaacg ttttgtactc caacgtagcc 1440ctctacttgc ctgacaagct taagtatact ccatccaatg tgcaaatttc caacaatccc 1500aactcctacg attacatgaa caagcgagtg gtggccccgg ggctggtgga ctgctacatc 1560aacctgggcg cgcgctggtc gctggactac atggacaacg tcaacccctt caaccaccac 1620cgcaatgcgg gcctgcgcta ccgctccatg ctcctgggca acgggcgcta cgtgcccttc 1680cacatccagg tgccccagaa gttctttgcc atcaagaacc tcctcctcct gccgggctcc 1740tacacctacg agtggaactt caggaaggat gtcaacatgg tcctccagag ctctctgggt 1800aacgatctca gggtggacgg ggccagcatc aagttcgaga gcatctgcct ctacgccacc 1860ttcttcccca tggcccacaa cacggcctcc acgctcgagg ccatgctcag gaacgacacc 1920aacgaccagt ccttcaatga ctacctttcc gccgccaaca tgctctaccc catacccgcc 1980aacgccacca acgtccccat ctccatcccc tcgcgcaact gggcggcctt ccgcggctgg 2040gccttcaccc gcctcaagac caaggagacc ccctccctgg gctcgggatt cgacccctac 2100tacacctact cgggctccat tccctacctg gacggcacct tctacctcaa ccacactttc 2160aagaaggtct cggtcacctt cgactcctcg gtcagctggc cgggcaacga ccgtctgctc 2220acccccaacg agttcgagat caagcgctcg gtcgacgggg agggctacaa cgtggcccag 2280tgcaacatga ccaaggactg gttcctggtc cagatgctgg ccaactacaa catcggctac 2340cagggcttct acatcccaga gagctacaag gacaggatgt actccttctt caggaacttc 2400cagcccatga gccggcaggt ggtggaccag accaagtaca aggactacca ggaggtgggc 2460atcatccacc agcacaacaa ctcgggcttc gtgggctacc tcgcccccac catgcgcgag 2520ggacaggcct accccgccaa cttcccctac ccgctcatag gcaagaccgc ggtcgacagc 2580atcacccaga aaaagttcct ctgcgaccgc accctctggc gcatcccctt ctccagcaac 2640ttcatgtcca tgggtgcgct ctcggacctg ggccagaact gctctacgc caactccgcc 2700cacgccctcg acatgacctt cgaggtcgac cccatggacg agcccaccct tctctatgtt 2760ctgttcgaag tctttgacgt ggtccgggtc caccagccgc accgcggcgt catcgagacc 2820gtgtacctgc gtacgccctt ctcggccggc aacgccacca cctaa 2865210172112823212DNA
213黑猩猩腺病毒-ChAd 4六鄰體40017atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaaaaagact 420ggcaataatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tgacgataat 540gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660tatggctcat ttgccagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720ggagatgtta agtcatttga catagaccta gccttctttg atattcccaa ttctggcgcg 780ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctcaaag 900gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320tgcaaaggca atatctatgc catggagatc aacctccagg ccaacctgtg gagaagtttt 1380ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500ctggtggacg cctacatcaa catcggggcg cgctggtcgc tggaccccat ggacaacgtg 1560aatcccttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1620gggcgctacg tgcccttcca catccaggtg ccccagaaat ttttcgccat caagagcctc 1680ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860
atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980gccgccttcc gcggctggtc cttcacgcgc ctcaagaccc gcgagacgcc ctcgctgggc 2040tccgggttcg acccctactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100tacctcaacc acaccttcaa gaaggtctcc atcaccttcg actcctccgt cagctggccc 2160ggcaacgacc gcctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggagag 2220ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340tccttcttcc gcaacttcca gcccatgagc cgccaggtgg tggacgaggt caactacaag 2400gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460gcgcccacca tgcgccaggg ccagccctac cccgccaact acccgtaccc gctcatcgga 2520aagagcgccg tcaccagcgt cacccagaaa aagttcctct gcgacagggt catgtggcgc 2580atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg ccagaacatg 2640ctctatgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa cgccaccacc 2820taa2823210182112823212DNA213黑猩猩腺病毒-ChAd 5六鄰體40018atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaaaaagact 420ggcaataatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tgacgataat 540gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660
tatggctcat ttgccagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720ggagatgtta agtcatttga catagaccta gccttctttg atattcccaa ttctggcgcg 780ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctcaaag 900gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320tgcaaaggca atatctatgc catggagatc aacctccagg ccaacctgtg gagaagtttt 1380ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500ctggtggacg cctacatcaa catcggggcg cgctggtcgc tggaccccat ggacaacgtg 1560aatcccttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1620gggcgctacg tgcccttcca catccaggtg ccccagaaat tttttgccat caagagcctc 1680ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980gccgccttcc gcggctggtc cttcacgcgc ctcaagaccc gcgagacgcc ctcgctgggc 2040tccgggttcg acccctactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100tacctcaacc acaccttcaa gaaggtctcc atcaccttcg actcctccgt cagctggccc 2160ggcaacgacc gcctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggagag 2220ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340tccttcttcc gcaacttcca gcccatgagc cgccaggtcg tggacgaggt caactacaag 2400gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460gcgcccacca tgcgccaggg ccagccctac cccgccaact acccctaccc gctcatcggc 2520aagagcgccg tcgccagcgt cacccagaaa aagttcctct gcgaccgggt catgtggcgc 2580atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg ccagaacatg 2640ctctacgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760
cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa agccaccacc 2820taa 2823210192112823212DNA213黑猩猩腺病毒-ChAd 7六鄰體40019atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccttactc cggcaccgct 360tacaacagcc tggcccccaa gggagcaccc aattccagcc agtgggagca aaaaaagact 420ggcaaaaatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tggcgataat 540gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660tatggctcat ttgctagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720ggagatgtta agtcatttga catagaccta gccttctttg atattccaaa ttctggcgcg 780ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctccgag 900gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320tgcaaaggca atatctatgc catggagatc aatctccagg ccaacctgtg gagaagtttc 1380ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500ctggtggatg cctacatcaa catcggagcg cgctggtcgc tggaccccat ggacaacgtc 1560
aatcccttca accaccaccg caatgcgggg ctgcgctacc gctccatgct cctgggcaac 1620gggcgctacg tgcccttcca catccaggtg ccccagaaat ttttcgccat caagagcctt 1680ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980gccgccttcc gcggctggtc cttcacgcgc ctcaagacca aggagacgcc ctcgctgggc 2040tccgggttcg acccatactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100tacctcaacc acaccttcaa gaaggtctcc atcaccttcg attcctccgt cagctggccc 2160ggcaacgacc ggctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggcgag 2220ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340tccttcttcc gcaacttcca gcccatgagc cgccaggtgg tggacgaggt caactacaag 2400gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460gcgcccacca tgcgccaggg ccagccctac cccgccaact acccgtaccc gctcatcggc 2520aagagcgccg tcaccagcgt cacccagaaa aagttcctct gcgacagggt catgtggcgc 2580atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg gcagaacatg 2640ctctatgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa cgccaccacc 2820taa 2823210202112793212DNA213黑猩猩腺病毒-ChAd 9六鄰體40020atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcacccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgct 360
tacaacagcc tggctcccaa gggagcgccc aacacttgcc agtggacata tactgataac 420caaactgaga aaacagccac atatggaaat gcacccgtag agggcattaa cattacaaaa 480gatggcattc aacttggaac tgacagcgat ggtcaggcaa tctatgcaga cgaaacttat 540cagcccgaac ctcaggtggg agatcctgaa tggcatgata ccacaggtac agaagaaaaa 600tatggaggca gagcgcttaa acctgccacc gacatgaaac cttgctatgg ctcttttgcc 660aagccaacta atgttaaggg aggtcaggcc aaaagcagaa caaaaactga tggaacaact 720gagcctgata ttgacatggc cttttttgat ggcagaaatg caacaacagc tggtttgact 780ccagaaattg ttttgtatac tgaaaatgtg gatctggaaa ctccagatac ccatattgta 840tacaaggcag gcacagatga cagcagctct tctatcaatt tgggtcagca gtccatgccc 900aacagaccca actacattgg cttcagagac aactttatcg ggctcatgta ctacaacagc 960actggcaata tgggtgtact ggctggacag gcctcccagc tgaatgctgt ggtggacttg 1020caggacagaa acactgaact gtcctaccag ctcttgcttg actctctggg tgacagaacc 1080aggtatttca gtatgtggaa tcaggcggtg gacagttatg accccgatgt gcgcattatt 1140gaaaatcacg gtgtggagga tgaactcccc aactattgct tccccctgaa tgctgtgggt 1200agaacaaata gttatcaggg aattaaaccc aatggaggcg atccagctac atgggccaaa 1260gatgaaagcg tcaatgattc taatgaattg ggcaagggca atcctttcgc catggagatc 1320aacatccagg ccaacctgtg gcggaacttc ctctacgcga acgtggcgct gtacctgccc 1380gactcctaca agtacacgcc ggccaacatc acgctgcccg ccaacaccaa cacctacgat 1440tacatgaacg gccgcgtggt ggcgccctcg ctggtggacg cctacatcaa catcggggcg 1500cgctggtcgc tggaccccat ggacaacgtc aaccccttca accaccaccg caacgcgggc 1560ctgcgctacc gctccatgct cctgggcaac gggcgctacg tgcccttcca catccaggtg 1620ccccaaaagt ttttcgccat caagagcctc ctgctcctgc ccgggtccta cacctacgag 1680tggaacttcc gcaaggacgt caacatgatc ctgcagagct ccctcggcaa cgacctgcgc 1740acggacgggg cctccatcgc cttcaccagc atcaacctct acgccacctt cttccccatg 1800gcgcacaaca ccgcctccac gctcgaggcc atgctgcgca acgacaccaa cgaccagtcc 1860ttcaacgact acctctcggc ggccaacatg ctctacccca tcccggccaa cgccaccaac 1920gtgcccatct ccatcccctc gcgcaactgg gccgccttcc gcggatggtc cttcacgcgc 1980ctcaagaccc gcgagacgcc ctcgctaggc tccgggttcg acccctactt cgtctactcg 2040ggctccatcc cctacctcga cggcaccttc tacctcaacc acaccttcaa gaaggtctcc 2100atcaccttcg actcctccgt cagctggccc ggcaacgacc gcctcctgac gcccaacgag 2160ttcgaaatca agcgcaccgt cgacggagag ggatacaacg tggcccagtg caacatgacc 2220aaggactggt tcctggtcca gatgctggcc cactacaaca tcggctacca gggcttctac 2280gtgcccgagg gctacaagga ccgcatgtac tccttcttcc gcaacttcca gcccatgagc 2340cgccaggtcg tggacgaggt caactacaag gactaccagg ccgtcaccct ggcctaccag 2400cacaacaact cgggcttcgt cggctacctc gcgcccacca tgcgccaggg ccagccctac 2460
cccgccaact acccctaccc gctcatcggc aagagcgccg tcgccagcgt cacccagaaa 2520aagttcctct gcgaccgggt catgtggcgc atccccttct ccagcaactt catgtccatg 2580ggcgcgctca ccgacctcgg ccagaacatg ctctacgcca actccgccca cgcgctagac 2640atgaatttcg aagtcgaccc catggatgag tccacccttc tctatgttgt cttcgaagtc 2700ttcgacgtcg tccgagtgca ccagccccac cgcggcgtca tcgaggccgt ctacctgcgc 2760acgcccttct cggccggcaa cgccaccacc taa 2793210212112793212DNA213黑猩猩腺病毒-ChAd 10六鄰體40021atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggctcccaa gggagcgccc aacacttgcc agtggacata tactgataac 420caaactgaga aaacagccac atatggaaat gcgcctgtgc aaggcattag tattacaaaa 480gatggtattc aacttggaac tgacactgat gatcagccca tttatgcaga taaaacttat 540caaccagagc ctcaagtggg tgatgctgaa tggcatgaca tcactggtac tgatgaaaaa 600tatggaggca gagctctcaa gcctgacacc aaaatgaagc cctgctatgg ttcttttgcc 660aagcctacca ataaagaagg aggtcaggca aatgtgaaaa ccgaaacagg cggtaccaaa 720gaatatgaca ttgacatggc attcttcgat aatcgaagtg cagctgcggc tggcctggcc 780ccagaaattg ttttgtatac tgagaatgtg gatctggaaa ctccagatac tcatattgta 840tacaaggcag gcacagatga cagcagctct tctatcaatt tgggtcagca gtccatgccc 900aacagaccca actacattgg cttcagagac aactttatcg gtctcatgta ctacaacagc 960actggcaata tgggtgtact ggctggtcag gcctcccagc tgaatgctgt ggtggacttg 1020caggacagaa acactgaact gtcctaccag ctcttgcttg actctctggg tgacagaacc 1080aggtatttta gtatgtggaa tcaggcggtg gacagttatg accccgatgt gcgcattatt 1140gaaaatcacg gtgtggagga tgaactccct aattattgct tcccccttaa tgctgtgggt 1200agaactgata cttaccaggg aattaaggcc aatggtgctg atcaaaccac atggaccaaa 1260gatgatactg ttaatgatgc taatgaattg ggcaagggca atcctttcgc catggagatc 1320
aacatccagg ccaacctgtg gcggaacttc ctctacgcga acgtggccct gtacctgccc 1380gactcctaca agtacacgcc ggccaacatc acgctgccca ccaacaccaa cacctacgat 1440tacatgaacg gccgcgtggt ggcgccctcg ctggtggacg cctacatcaa catcggggcg 1500cgctggtcgc tggaccccat ggacaacgtc aaccccttca accaccaccg caacgcgggc 1560ctgcgctacc gctccatgct cctgggcaac gggcgctacg tgcccttcca catccaggtg 1620ccccaaaagt tcttcgccat caagagcctc ctgctcctgc ccgggtccta cacctacgag 1680tggaacttcc gcaaggacgt caacatgatc ctgcagagct ccctcggcaa cgacctgcgc 1740acggacgggg cctccatcgc cttcaccagc atcaacctct acgccacctt cttccccatg 1800gcgcacaaca ccgcctccac gctcgaggcc atgctgcgca acgacaccaa cgaccagtcc 1860ttcaacgact acctctcggc ggccaacatg ctctacccca tcccggccaa tgccaccaac 1920gtgcccatct ccatcccctc gcgcaactgg gccgccttcc gcggatggtc cttcacgcgc 1980ctcaagaccc gcgagacgcc ctcgctaggc tccgggttcg acccctactt cgtctactcg 2040ggctccatcc cctacctcga cggcaccttc tacctcaacc acaccttcaa gaaggtctcc 2100atcaccttcg actcctccgt cagctggccc ggcaacgacc gcctcctgac gcccaacgag 2160ttcgaaatca agcgcaccgt cgacggagag gggtacaacg tggcccagtg caacatgacc 2220aaggactggt tcctggtcca gatgctggcc cactacaaca tcggctacca gggcttctac 2280gtgcccgagg gctacaagga ccgcatgtac tccttcttcc gcaacttcca gcccatgagc 2340cgccaggtcg tggacgaggt caactacaag gactaccagg ccgtcaccct ggcctaccag 2400vcacaacaactcgggcttcgt cggctacctc gcgcccacca tgcgccaggg ccagccctac 2460cccgccaact acccctaccc gctcatcggc aagagcgccg tcgccagcgt acccagaaa2520aagttcctct gcgaccgggt catgtggcgc atccccttct ccagcaactt catgtccatg 2580ggcgcgctca ccgacctcgg ccagaacatg ctctacgcca actccgccca cgcgctagac 2640atgaatttcg aagtcgaccc catggatgag tccacccttc tctatgttgt cttcgaagtc 2700ttcgacgtcg tccgagtgca ccagccccac cgcggcgtca tcgaggccgt ctacctgcgc 2760acgcccttct cggccggcaa cgccaccacc taa2793210222112883212DNA213黑猩猩腺病毒-ChAd 11六鄰體40022atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagtcccgg gctggtgcag ttcgctcgcg ccaccgagag ctacttcagt 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcy 360tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420caggcagttg aagaagcagc agaagaggag gaagaagatg ctgacggtca agctgaggaa 480gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc cggcgaaaaa 540attagcaaag acggtctgca gataggaacg gacgctacag caaccgaaca aaaacctatt 600tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcccagtg gaatgaggca 660gatgctacag tcgctggtgg tagagtgctc aagaaaacca ctcccatgaa accatgctat 720ggttcctatg caagacccac gaatgctaat ggaggtcagg gtgtactagc ggcaaatgcc 780caaggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840aacgaggcta acaacattca gcccaaattg gtgctgtata gcgaggatgt gcacatggag 900accccggata cacacctctc ttacaagccc acaaaaagcg atgacaattc taaagttatg 960ctgggccaac aggccatgcc caacaggcct aattacattg gcttcagaga caactttatc 1020ggtctcatgt actacaacag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140gattccatgg gtgacagaac cagatatttc tccatgtgga atcaggcagt ggacagttat 1200gacccagatg tcagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260ttccctctgg gcggcatagg gtaactgac acttaccagg ctgttaagac caacaatggc 1320aataatgggg gtcaggtgac ttggacaaaa gatgaaactt ttgcagagcg caatgagata 1380ggggtgggaa acaatttcgc catggagatc aacctcaatg ccaacctgtg gaggaacttc 1440ctgtactcca acgtggccct gtacctgcca gacaagctta agtacaaccc ctccaacgtg 1500gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620aaccctttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1680gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800ctccagagct ctctgggcaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860vatctgcctc acgccacctt cttccccatg gcccacaaca ccgcctccac gctcgaggcc 1920atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctctccgc cgccaacatg 1980ctctacccca tccccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100tcgggattcg acccctacta cacctactcg ggatccattc cctacctgga cggcaccttc 2160tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220ggcaacgacc gcctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggag 2280
ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctaccc gctcataggc 2580aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640atccccttct ccagcaactt catgtccatg ggtgcgctca cggacctggg ccagaacctg 2700ctctatgcca actccgccca cgcgctcgac atgaccttcg aggtcgaccc catggacgag 2760cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820cgcggcgtca tcgagaccgt gtacctgcgc acgcccttct cggccggcaa cgccaccacc 2880taa2883210232112835212DNA213黑猩猩腺病毒-ChAd 16六鄰體40023atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggcccccaa gggagctccc aattccagtc agtgggagca gacggagaac 420gggggcggac aggctacgac taaaacacac acctatggag ttgccccaat gggtggaact 480aatattacag tcgacggact acaaattgga actgacgcta cagctgatac ggaaaaacca 540atttatgctg ataaaacatt ccaacctgag cctcagatag gagaggaaaa ctggcaagaa 600actgaaagct tttatggcgg tagggctctt aagaaagaca caaacatgaa gccttgttat 660ggctcatttg ccagacctac caatgaaaag gaggtcaag ctaaacttaa agttggagct 720gatgggctgc cgaccaaaga atttgacata gacctagcat tctttgatac tcctggtggc 780actgtgaccg gaggtacaga ggagtataaa gcagatattg ttatgtatac cgaaaacacg 840tatctggaaa ctccagacac acatgtggtg tataaaccag gcaaggataa cacaagttct 900aaaattaacc tggtccagca gtctatgccc aacaggccca actacattgg gtttagggac 960aactttattg ggctcatgta ttacaacagc actggcaata tgggtgtgct ggccggtcag 1020
gcttctcagt tgaatgctgt ggttgacttg caagacagaa acactgaact gtcttaccag 1080ctcttgcttg actctttggg tgacagaacc aggtatttca gtatgtggaa tcaggcggtg 1140gacagttatg atcctgatgt gcgcattatt gaaaaccatg gtgtggaaga tgaacttccc 1200aactattgct tccccctgga tgggtctggc actaacgccg cttaccaagg tgtgaaagta 1260aaaaatggtc aagatggtga tgttgagagc gaatgggaaa aagatgatac tgtcgcagct 1320cgaaatcaat tatgcaaggg caacattttt gccatggaga tcaatctcca ggccaacctg 1380tggagaagtt ttctctactc gaacgtggcc ctgtacctgc ccgattctta caagtacacg 1440ccggccaaca tcaccctgcc caccaacacc aacacctacg attacatgaa cgggagagtg 1500gtgcctccct cgctggtgga cgcctacatc aacatcgggg cgcgctggtc gctggacccc 1560atggacaacg tcaatccctt caaccaccat cgcaacgcgg ggctgcgcta ccgctccatg 1620ctcctgggca acgggcgcta cgtgcccttc cacatccagg tgccccagaa atttttcgcc 1680attaagagcc tcctgctcct gcccgggtcc tacacctacg agtggaactt ccgcaaggac 1740gtcaacatga tcctgcagag ctccctcggc aacgacctgc gcacggacgg ggcctccatc 1800tccttcacca gcatcaacct ctacgccacc ttcttcccca tggcgcacaa caccgcctcc 1860acgctcgagg ccatgctgcg caacgacacc aacgaccagt ccttcaacga ctacctctcg 1920gcggccaaca tgctctaccc catcccggcc aacgccacca acgtgcccat ctccatcccc 1980tcgcgcaact gggccgcctt ccgcggctgg tccttcacgc gcctcaagac caaggagacg 2040ccctcgctgg gctccgggtt cgacccctac ttcgtctact cgggctccat cccctacctc 2100gacggcacct tctacctcaa ccacaccttc aagaaggtct ccatcacctt cgactcctcc 2160gtcagctggc ccggcaacga ccggctcctg acgcccaacg agttcgaaat caagcgcacc 2220gtcgacggcg agggctacaa cgtggcccag tgcaacatga ccaaggactg gttcctggtc 2280cagatgctgg cccactacaa catcggctac cagggcttct acgtgcccga gggctacaag 2340gaccgcatgt actccttctt ccgcaacttc cagcccatga gccgccaggt cgtggacgag 2400gtcaactaca aggactacca ggccgtcacc ctggcctacc agcacaacaa ctcgggcttc 2460gtcggctacc tcgcgcccac catgcgccag ggccagccct accccgccaa ctacccctac 2520ccgctcatcg gcaagagcgc cgtcgccagc gtcacccaga aaaagttcct ctgcgaccgg 2580gtcatgtggc gcatcccctt ctccagcaac ttcatgtcca tgggcgcgct caccgacctc 2640ggccagaaca tgctctacgc caactccgcc cacgcgctag acatgaattt cgaagtcgac 2700cccatggatg agtccaccct tctctatgtt gtcttcgaag tcttcgacgt cgtccgagtg 2760caccagcccc accgcggcgt catcgaggcc gtctacctgc gcaccccctt ctcggccggt 2820aacgccacca cctaa 2835210242112883212DNA
213黑猩猩腺病毒-ChAd 17六鄰體40024atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcngagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420caggcagttg aagaagcagc agaagaggaa gaagaagatg ctgacggtca agctqaggaa 480gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc tggcgaaaaa 540attagtaaag atggtctgca aataggaacg gacgctacag ctacagaaca aaaacctatt 600tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcacagtg gaatgaggca 660gatgctacag tcgccggcgg tagagtgcta aagaaatcta ctcccatgaa accatgctat 720ggttcctatg caagacccac aaatgctaat ggaggtcagg gtgtactaac ggcaaatgcc 780cagggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840aacgagacta acaacattca gcccaaattg gtgctgtata gtgaggatgt gcacatggag 900accccggata cgcacctttc ttacaagccc gcaaaaagcg atgacaattc aaaaatcatg 960ctgggtcagc agtccatgcc caacagacct aattacatcg gcttcagaga taactttatc 1020ggcctcatgt attacaatag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140gattccatgg gtgacagaac cagatacttt tccatgtgga atcaggcagt ggacagttat 1200gacccagatg ttagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260ttccctctgg gtggcatagg ggtaactgac acttaccagg ctgttaaaac caacaatggc 1320aataacgggg gccaggtgac ttggacaaaa gatgaaactt ttgcagatcg caatgaaata 1380ggggtgggaa acaatttcgc tatggagata aacctcagtg ccaacctgtg gagaaacttc 1440ctgtactcca acgtggcgct gtacctacca gacaagctta agtacaaccc ctccaatgtg 1500gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620aaccccttca accaccaccg caatgcgggc ctgcgctacc gctccatgct cctgggcaac 1680gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800ctccagagct ctctgggtaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860
atctgcctct acgccacctt cttccccatg gcccacaaca cggcctccac gctcgaggcc 1920atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctctccgc cgccaacatg 1980ctctacccca tacccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100tcgggattcg acccctacta cacctactcg ggctccattc cctacctgga cggcaccttc 2160tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220ggcaacgacc gtctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggag 2280ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctatcc gctcataggc 2580aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640atccccttct ccagcaactt catgtccatg ggtgcgctct cggacctggg ccagaacttg 2700ctctacgcca actccgccca cgccctcgac atgaccttcg aggtcgaccc catggacgag 2760cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820cgcggcgtca tcgagaccgt gtacctgcgt acgcccttct cggccggcaa cgccaccacc 2880taa2883210252112877212DNA213黑猩猩腺病毒-ChAd 19六鄰體40025atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagt 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcc 360tacaactccc tggcccccaa gggcgctccc aactcttgtg agtgggagca attagaagaa 420gcccaggccg ctttggaaga cgaagaatta gaagatgaag acgaggaacc acaggatgag 480gcgcctgtga aaaagaccca tgtatacgct caggctcccc tttctggaga agaaattact 540aaagacggtt tgcaaatagg gtcagataac acagaagctc agtctaagcc tatatatgca 600
gaccctacat tccagcccga accccaaatc ggggagtccc agtggaacga ggcagatgct 660acagtcgctg gtggtagagt gctcaagaaa accactccca tgaaaccatg ctatggttcc 720tatgcaagac ccacgaatgc taatggaggt cagggtgtgc tggtggctga tgataagggg 780gtccttcaat ctaaagttga attgcaattt ttttcaaata ctactactct taatcagcgg 840gagggtaatg atacaaaacc aaaagtagtg ctgtatagcg aggatgtgca catggaaaca 900ccagacaccc acatttctta caagcccaca aaaagcgatg acaattctaa agttatgctg 960ggccaacagt ccatgcccaa caggcctaat tacatcggct tcagagacaa ctttatcggt 1020ctcatgtact acaacagcac tggcaacatg ggagtgcttg caggtcaggc ctctcagttg 1080aatgcagtgg tggacttgca agacagaaac acagaactgt cctaccagct cttgcttgat 1140tccatgggtg acagaaccag atatttctcc atgtggaatc aggcagtgga cagttatgac 1200ccggatgtca gaattattga aaatcatgga accgaagacg agctccccaa ctattgtttt 1260cctctgggtg gcataggggt aactgacact taccaggtca ttaaaactaa tggcaatggt 1320caagcagacc caacctggga aaaagataca gagtttgcag accgcaatga aataggggtg 1380ggaaacaatt tcgccatgga gatcaacctc aatgccaacc tgtggaggaa cttcctgtac 1440tccaacgtgg ccctgtacct gccagacaag cttaagtaca acccctccaa cgtggacatc 1500tctgacaacc ccaacaccta cgattacatg aacaagcgag tggtggcccc ggggctggtg 1560gactgctaca tcaacctggg cgcgcgctgg tcgctggact acatggacaa cgtcaacccc 1620ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680tacgtgccct tccacatcca ggtgccccag aagttctttg ccatcaagaa cctcctcctc 1740ctgccgggct cctacaccta cgagtggaac ttcaggaagg atgtcaacat ggtcctccag 1800agctctttgg gcaacgatct cagggtggac ggggccagca tcaagttcga gagcatctgc 1860ctctacgcca ccttcttccc catggcccac aacaccgcct ccacgctcga ggccatgctc 1920aggaacgaca ccaacgacca gtccttcaat gactacctct ccgccgccaa catgctctac 1980cccatccccg ccaacgccac caacgtccct atctccatcc cctcgcgcaa ctgggcggcc 2040ttccgcggct gggccttcac ccgcctcaag accaaggaga caccctccct gggctcggga 2100ttcgacccct actacaccta ctcgggatcc attccctacc tggacggcac cttctacctc 2160aaccacactt tcaagaaggt ctcggtcacc ttcgactcct cggtcagctg gccgggcaac 2220gaccgcctgc tcacccccaa cgagttcgag atcaagcgct cggtcgacgg ggagggctac 2280aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggccaactac 2340aacatcggct accagggctt ctacatccca gagagctaca aggacaggat gtactccttc 2400ttcaggaact tccagcccat gagccggcag gtggtggacc aaaccaagta caaggactac 2460caggaggtgg gcatcatcca ccagcacaac aactcgggct tcgtgggcta cctcgccccc 2520accatgcgcg agggacaggc ctaccccgcc aacttcccct acccgctcat aggcaagacc 2580gcggtcgaca gcatcaccca gaaaaagttc ctctgcgacc gcaccctctg gcgcatcccc 2640ttctccagca acttcatgtc catgggtgcg ctcacggacc tgggccagaa cctgctctat 2700
gccaactccg cccacgcgct cgacatgacc ttcgaggtcg accccatgga cgagcccacc 2760cttctctatg ttctgttcga agtctttgac gtggtccggg tccaccagcc gcaccgcggc 2820gtcatcgaga ccgtgtacct gcgcacgccc ttctcggccg gcaacgccac cacctaa28772102621149212DNA213人工序列220
223polA40026aataaaagat ctttattttc attagatctg tgtgttggtt ttttgtgtg 492102721137212DNA213人工序列220
223寡聚物40027atggaattcg tttaaaccat catcaataat atacctc 372102821123212DNA213人工序列220
223寡聚物
40028cgctggcact caagagtggc ctc 232102921137212DNA213人工序列220
223寡聚物40029atgaagcttg tttaaaccca tcatcaataa tatacct 372103021126212DNA213人工序列220
223寡聚物40030atctagacag cgtccatagc ttaccg 262103121144212DNA213人工序列220
223寡聚物40031
atgctacgta gcgatcgcgt gagtagtgtt tgggggtggg tggg 442103221133212DNA213人工序列220
223寡聚物40032taggcgcgcc gcttctcctc gttcaggctg gcg 332103321138212DNA213人工序列220
223寡聚物40033gatctagtta gtttaaacga attcggatct gcgacgcg 382103421137212DNA213人工序列220
223寡聚物40034ttcgatcatg tttaaacgaa attaagaatt cggatcc 37
2103521133212DNA213人工序列220
223寡聚物40035tattctgcga tcgctgaggt gggtgagtgg gcg332103621131212DNA213人工序列220
223寡聚物40036tagg cgcgcc cttaaacggc atttgtggga g 312103721127212DNA213人工序列220
223寡聚物40037cgtctagaag acccgagtct taccagt 2721038
21139212DNA213人工序列220
223
40038cgggatccgt ttaaaccatc atcaataata taccttatt392103921137212DNA213人工序列220
223寡聚物40039atggaattcg tttaaaccat catcaataat atacctt372104021145212DNA213人工序列220
223寡聚物40040atgacgcgat cgctgatatc ctataataat aaaacgcaga ctttg 45210412112880212DNA
213黑猩猩腺病毒-ChAd 3六鄰體40041atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420caggcagttg aagaagcagc agaagaggaa gaagaagatg ctgacggtca agctgaggaa 480gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc tggcgaaaaa 540attagtaaag atggtctgca aataggaacg gacgctacag ctacagaaca aaaacctatt 600tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcccagtg gaatgaggca 660gatgctacag tcgccggcgg tagagtgcta aagaaatcta ctcccatgaa accatgctat 720ggttcctatg caagacccac aaatgctaat ggaggtcagg gtgtactaac ggcaaatgcc 780cagggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840aacgaggcta acaacattca gcccaaattg gtgctgtata gtgaggatgt gcacatggag 900accccggata cgcacctttc ttacaagccc gcaaaaagcg atgacaattc aaaaatcatg 960ctgggtcagc agtccatgcc caacagacct aattacatcg gcttcagaga caactttatc 1020ggcctcatgt attacaatag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140gattccatgg gtgacagaac cagatacttt tccatgtgga atcaggcagt ggacagttat 1200gacccagatg ttagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260ttccctctgg gtggcatagg ggtaactgac acttaccagg ctgttaaaac caacaatggc 1320aataacgggg gccaggtgac ttggacaaaa gatgaaactt ttgcagatcg caatgaaata 1380ggggtgggaa acaatttcgc tatggagatc aacctcagtg ccaacctgtg gagaaacttc 1440ctgtactcca acgtggcgct gtacctacca gacaagctta agtacaaccc ctccaatgtg 1500gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620aaccccttca accaccaccg caatgcgggc ctgcgctacc gctccatgct cctgggcaac 1680gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800ctccagagct ctctgggtaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860
atctgcctct acgccacctt cttccccatg gcccacaaca cggcctccac gctcgaggcc 1920atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctttccgc cgccaacatg 1980ctctacccca tacccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100tcgggattcg acccctacta cacctactcg ggctctattc cctacctgga cggcaccttc 2160tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220ggcaacgacc gtctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggaa 2280ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctaccc gctcataggc 2580aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640atccccttct ccagcaactt catgtccatg ggtgcgctct cggacctggg ccagaacttg 2700ctctacgcca actccgccca cgccctcgac atgaccttcg aggtcgaccc catggacgag 2760cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820cgcggcgtca tcgagaccgt gtacctgcgt acgcccttct cggccggcaa cgccaccacc 2880210422111683212DNA213黑猩猩腺病毒-ChAd 3纖維40042atgtcagatt cttgctcctg tccctccgca cccactatct tcatgttgtt gcagatgaag 60cgcaccaaaa cctctgacga gagcttcaac cccgtgtacc cctatgacac ggaaagcggc 120cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagaaagc 180ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc 240gccctgaaaa tgggaagtgg cctctccctg gacgacgctg gcaacctcac ctctcaagat 300atcaccaccg ctagccctcc cctcaaaaaa accaagacca acctcagcct agaaacctca 360tcccccctaa ctgtaagcac ctcaggcgcc ctcaccgtag cagccgccgc tcccctggca 420gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa 480ctcaccctgg ccaccaaagg ccccctgacc gtgtctgaag gcaaactggc cttgcaaaca 540tcggccccgc tgacggccgc tgacagcagc accctcaccg ttagcgccac accaccaatt 600
aatgtaagca gtggaagttt aggcttagac atggaagacc ctatgtatac tcacgatgga 660aaactgggaa taagaattgg gggtccacta agagtagtag acagcttgca cacactcact 720gtagttaccg gaaatggact aactgtagat aacaatgccc tccaaactag agttacgggc 780gccctaggtt atgacacatc aggaaatcta caattgagag ctgcaggagg tatgcgaatt 840gatgcaaatg gccaacttat ccttaatgtg gcatacccat ttgatgctca gaacaatctc 900agccttagac ttggtcaggg acccctgtat ataaacacag accacaacct ggatttgaat 960tgcaacagag gtctaaccac aactaccacc aacaacacaa aaaaacttga gactaaaatt 1020agctcaggct tagactatga caccaatggt gctgtcatta ttaaacttgg cactggtcta 1080agcttcgaca acacaggcgc cctaactgtg ggaaacactg gtgatgataa actgactctg 1140tggacgaccc cagacccatc tccaaattgc agaattcact cagacaaaga ctgcaagttt 1200actctagtcc taactaagtg tggaagccaa atcctggcct ctgtcgccgc cctagcggta 1260tcaggaaatc tggcttcgat aacaggcacc gttgccagcg ttaccatctt tctcagattt 1320gatcagaatg gagtgcttat ggaaaactcc tcgctagaca ggcagtactg gaacttcaga 1380aatggcaact caactaacgc tgccccctac accaatgcag ttgggttcat gccaaacctc 1440gcagcatacc ccaaaacgca aagccagact gctaaaaaca acattgtaag tcaggtttac 1500ttgaatggag acaaatccaa acccatgacc cttaccatca ccctcaatgg aactaatgaa 1560tccagtgaaa ctagccaggt gagtcactac tccatgtcat ttacatgggc ttgggaaagt 1620gggcaatatg ccactgaaac ctttgccacc aactccttca ccttttctta cattgctgaa 1680caa1683210432112859212DNA213黑猩猩腺病毒-ChAd 6六鄰體40043atgtatgtcc gccgaccaga aggaagaggc gcgtcgccga gttgcaagat ggccacccca 60tcgatgctgc cccagtgggc gtacatgcac atcgccggac aggacgcttc ggagtacctg 120agtccgggtc tggtgcagtt cgcccgcgcc acagacacct acttcagtct ggggaacaag 180tttaggaacc ccacggtggc gcccacgcac gatgtgacca ccgaccgcag ccagcggctg 240acgctgcgct tcgtgcccgt ggaccgcgag gacaacacct actcgtacaa agtgcgctac 300acgctggccg tgggcgacaa ccgcgtgctg gacatggcca gcacctactt tgacatccgc 360ggcgtgctgg atcggggccc cagcttcaaa ccctactccg gcaccgccta caacagcctg 420gctcccaagg gagcgcccaa cacctcacag tggataacca aagacaatgg aactgataag 480acatacagtt ttggaaatgc tccagtcaga ggattggaca ttacagaaga gggtctccaa 540
ataggacccg atgagtcagg gggtgaaagc aagaaaattt ttgcagacaa aacctatcag 600cctgaacctc agcttggaga tgaggaatgg catgatacta ttggagctga agacaagtat 660ggaggcagag cgcttaaacc tgccaccaac atgaaaccct gctatgggtc tttcgccaag 720ccaactaatg ctaagggagg tcaggctaaa agcagaacca aggacgatgg cactactgag 780cctgatattg acatggcctt ctttgacgat cgcagtcagc aagctagttt cagtccagaa 840cttgttttgt atactgagaa tgtcgatctg gacaccccgg atacccacat tatttacaaa 900cctggcactg atgaaacaag ttcttctttc aacttgggtc agcagtccat gcccaacaga 960cccaactaca tcggcttcag agacaacttt atcggtctca tgtactacaa cagtactggc 1020aatatgggtg tactagctgg acaggcctcc cagctgaatg ctgtggtgga cttgcaggac 1080agaaacactg aactgtccta ccagctcttg cttgactctc tgggtgacag aaccaggtat 1140ttcagtatgt ggaaccaggc ggtggacagc tacgaccccg atgtgcgcat tattgaaaat 1200cacggtgtgg aggatgaact acccaactat tgcttccctt tgaatggtgt gggctttaca 1260gatacattcc agggaattaa ggttaaaact accaataacg gaacagcaaa tgctacagag 1320tgggaatctg atacctctgt caataatgct aatgagattg ccaagggcaa tcctttcgcc 1380atggagatca acatccaggc caacctgtgg cggaacttcc tctacgcgaa cgtggcgctg 1440tacctgcccg actcctacaa gtacacgccg gccaacatca cgctgcccgc caacaccaac 1500acctacgatt acatgaacgg ccgcgtggta gcgccctcgc tggtggacgc ctacatcaac 1560atcggggcgc gctggtcgct ggaccccatg gacaacgtca accccttcaa ccaccaccgc 1620aacgcgggcc tgcgctaccg ctccatgctc ctgggcaacg ggcgctacgt gcccttccac 1680atccaggtgc cccaaaagtt tttcgccatc aagagcctcc tgctcctgcc cgggtcctac 1740acctacgagt ggaacttccg caaggacgtc aacatgatcc tgcagagctc cctcggcaac 1800gacctgcgca cggacggggc ctccatcgcc ttcaccagca tcaacctcta cgccaccttc 1860ttccccatgg cgcacaacac cgcctccacg ctcgaggcca tgctgcgcaa cgacaccaac 1920gaccagtcct tcaacgacta cctctcggcg gccaacatgc tctaccccat cccggccaac 1980gccaccaacg tgcccatctc catcccctcg cgcaactggg ccgccttccg cggctggtcc 2040ttcacgcgcc tcaagacccg cgagacgccc tcgctcggct ccgggttcga cccctacttc 2100gtctactcgg gctccatccc ctacctcgac ggcaccttct acctcaacca caccttcaag 2160aaggtctcca tcaccttcga ctcctccgtc agctggcccg gcaacgaccg cctcctgacg 2220cccaacgagt tcgaaatcaa gcgcaccgtc gacggagagg ggtacaacgt ggcccagtgc 2280aacatgacca aggactggtt cctggttcag atgctggccc actacaacat cggctaccag 2340ggcttctacg tgcccgaggg ctacaaggac cgcatgtact ccttcttccg caacttccag 2400cccatgagcc gccaggtcgt ggacgaggtc aactacaagg actaccaggc cgtcaccctg 2460gcctaccagc acaacaactc gggcttcgtc ggctacctcg cgcccaccat gcgccaggga 2520cagccctacc ccgccaacta cccctacccg ctcatcggca agagcgccgt cgccagcgtc 2580acccagaaaa agttcctctg cgaccgggtc atgtggcgca tccccttctc cagcaacttc 2640
atgtccatgg gcgcgctcac cgacctcggc cagaacatgc tctacgccaa ctccgcccac 2700gcgctagaca tgaatttcga agtcgacccc atggatgagt ccacccttct ctatgttgtc 2760ttcgaagtct tcgacgtcgt ccgagtgcac cagccccacc gcggcgtcat cgaggccgtc 2820tacctgcgca cgcccttctc ggccggtaac gccaccacc2859210442111335212DNA213黑猩猩腺病毒-ChAd 6纖維40044atgtccaaaa agcgcgcgcg ggtggatgat gacttcgacc ccgtgtaccc ctacgatgca 60gacaacgcac cgactgtgcc cttcatcaac cctcccttcg tctcttcaga tggattccaa 120gaaaagcccc tgggggtgtt gtccctgcga ctggccgatc ccgtcaccac caagaacggg 180gctgtcaccc tcaagctggg ggagggggtg gacctcgacg actcgggaaa actcatctcc 240aaaaatgcca ccaaggccac tgcccctctc agtatttcca acaacaccat ttcccttaac 300atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcagatactg 900ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggaaaagta 960accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaagc cagttcaaca 1020ctagataaag aatattggaa tttcagaaaa ggagatgtga cacctgctga cccctacact 1080aatgctatag gctttatgcc caaccttaat gcatacccaa aaaacacaaa cgcagctgca 1140aaaagtcaca ttgttggaaa agtataccta catggggatg aaagcaagcc actagacttg 1200ataattacat ttaatgaaac cagtgatgaa tcctgtactt attgcattaa ctttcagtgg 1260cagtggggaa ctgaccaata taaagatgaa acacttgcag tcagttcatt caccttctca 1320tacattgcta aagaa 1335
2104521122212DNA213人工序列220
223引物40045tgtcctacca rctcttgctt ga222104621118212DNA213人工序列220
223引物40046gtggaarggc acgtagcg 18210472119212PRT213HIV gag CD8表位220
223引物40047Ala Met Gln Met Leu Lys Glu Thr Ile1 5
21048211578212PRT213黑猩猩腺病毒-ChAd 20纖維40048Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp180 185 190Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe195 200 205Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val
210 215220Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val225 230 235 240Ser Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu Arg Ala245 250 255Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln275 280 285Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn290 295 300Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val305310 315 320Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala325 330 335Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp Ser Gly Ser Asp Thr Asn340 345 350Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Asp Tyr Asp Ser Ser Arg355 360 365Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly370 375 380Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr385 390 395 400Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala405 410 415Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser420 425 430Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr435 440 445Val Thr Ser Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly Val Leu450 455 460Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly465 470 475 480Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro
485 490 495Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn500 505 510Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr515 520 525Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val530 535 540Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr545 550 555 560Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala565 570 575Gln Glu21049211425212PRT213黑猩猩腺病毒-ChAd 4纖維40049Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asr Thr85 90 95Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu115 120 125Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser130 135 140Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly145 150 155 160Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp165 170 175Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp180 185 190Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser195 200 205Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu210 215 220Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn225 230 235 240Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro245 250 255Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu260265 270Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val275 280 285Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln290 295 300Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser305 310 315 320Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly325 330 335Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr340 345 350Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val355 360365Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu370 375 380Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser405 410 415Tyr Thr Phe Ser Tyr Ile Ala Gln Glu420 42521050211444212PRT213黑猩猩腺病毒-ChAd 5纖維40050Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Asp Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu100 105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115 120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn130 135 140Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala145 150 155 160Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala165 170175
Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe195 200 205Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln210 215 220Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Ser Leu225 230 235 240Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu275 280 285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295 300Leu Leu Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Arg305 310 315 320Thr Ala Leu Val Ser Leu Lys Phe Asn Ala Asn Gly Ala Leu Leu Asp325 330 335Lys Ser Thr Leu Asn Lys Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu340 345 350Ile Pro Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys355 360 365Lys Ala Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val370 375 380Gly Asp Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile385390 395 400Ile Thr Phe Asn Glu Thr Asp Asp Glu Thr Cys Asp Tyr Cys Ile Asn405 410 415Phe Gln Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala420 425 430Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 440
21051211445212PRT213黑猩猩腺病毒-ChAd 7纖維40051Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Asn Asn Asn Gly Lys Leu100105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Thr130 135 140Gly Ala Leu Val Ala Gln Leu Ala Ala Pro Leu Ala Phe Asp Ser Asn145 150 155 160Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala165 170 175Asn Arg Leu Asn Ile Asn Cys Asn Arg Gly Leu Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Thr Asn Ile Ser Trp Ala Asn Ala Met Thr Phe195 200 205Ile Gly Asn Ala Met Gly Val Asn Ile Asp Thr Gln Lys Gly Leu Gln
210 215 220Phe Gly Thr Thr Ser Thr Val Ala Asp Val Lys Asn Ala Tyr Pro Ile225 230 235 240Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Asp Lys Asp Ala Lys Leu275 280285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295300Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Gln Val305 310 315 320Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln325 330 335Thr Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp340 345350Val Thr Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn355 360 365Leu Lys Ala Tyr Pro Lys Asn Thr Ser Gly Ala Ala Lys Ser His Ile370 375 380Val Gly Lys Val Tyr Leu His Gly Asp Thr Asp Lys Pro Leu Asp Leu385 390 395 400Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile405 410 415Asn Phe Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Glu Thr Leu420 425430Ala Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 440 44521052211425212PRT
213黑猩猩腺病毒-ChAd 9纖維40052Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Ala Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu115 120 125Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser130 135 140Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly145 150 155 160Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp165 170 175Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp180 185 190Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser195 200 205Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu210 215 220Gly Ser Gly Leu Ser Phe Asp SerThr Gly Ala Ile Met Ala Gly Asn225 230235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro245 250 255Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu260 265 270Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val275 280 285Gly Ser Gly Asp Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln290 295 300Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser305 310 315 320Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly325 330 335Thr Pro Tyr Ala Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr340345 350Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val355 360365Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu370 375 380Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr385 390 395 400Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser405 410 415Tyr Thr Phe Ser Tyr Ile Ala Gln Glu420 42521053211425212PRT213黑猩猩腺病毒-ChAd 10纖維40053Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu115 120 125Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser130 135 140Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly145 150 155 160Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp165 170 175Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp180 185 190Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser195 200 205Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu210 215 220Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn225 230 235 240Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro245 250 255Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu260 265 270Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val275 280 285Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser305 310 315 320Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly325 330 335Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr340 345 350Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val355 360 365Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu370 375 380Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr385 390 395 400Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser405 410 415Tyr Thr Phe Ser Tyr Ile Ala Gln Glu420 42521054211578212PRT213黑猩猩腺病毒-ChAd 11纖維40054Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80
Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Leu Ala Ala Ala Val Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Ile165 170 175Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp180 185 190Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe195 200 205Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val210 215 220Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val225 230 235 240Ser Gly Ala Leu Asn Tyr Asp Ser Ser Gly Asn Leu Glu Leu Arg Ala245 250 255Ala Gly Gly Met Arg Val Asp Ala Asn Gly Lys Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln275 280 285Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn290 295 300Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val305 310 315 320Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala325 330 335Ile Asn Pro Gly Asp Gly Leu Glu Phe Gly Ser Gly Ser Asp Thr Asn340 345 350
Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Glu Tyr Asp Ser Ser Arg355 360 365Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly370 375 380Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr385 390 395 400Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala405 410 415Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser420 425 430Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr435 440 445Val Thr Ser Ala Gln Ile Ile Leu Arg Phe Asp Glu Asn Gly Val Leu450 455 460Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly465 470 475 480Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro485 490 495Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn500 505 510Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Ile515 520 525Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val530 535 540Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr545 550 555 560Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala565 570 575Gln Glu21055211442212PRT
213黑猩猩腺病毒-ChAd 16纖維40055Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Thr Met Gln Val Thr Ala Pro Leu Lys Leu Ala Asn Thr Ala Ile Leu115 120 125Asn Thr Leu Ala Met Ala Tyr Gly Asn Gly Leu Gly Leu Ser Asn Asn130 135 140Ala Leu Thr Val Gln Leu Gln Ser Pro Leu Thr Phe Asn Asn Ser Lys145 150 155 160Val Ala Ile Asn Leu Gly Asn Gly Pro Leu Asn Val Thr Ser Asn Arg165 170 175Leu Ser Ile Asn Cys Lys Arg Gly Val Tyr Val Thr Thr Thr Gly Asp180 185 190Ala Ile Glu Thr Asn Ile Ser Trp Ser Asn Ala Ile Lys Phe Ile Gly195 200 205Asn Ala Met Gly Val Asn Ile Asp Thr Asn Lys Gly Leu Gln Phe Gly210 215 220Thr Thr Ser Thr Val Thr Asp Val Thr Asn Ala Phe Pro Ile Gln Val225 230 235 240Lys Leu Gly Ala Gly Leu Ala Phe Asp Ser Thr Gly Ala Ile Val Ala
245 250 255Trp Asn Lys Glu Asp Asp Ser Leu Thr Leu Trp Thr Thr Pro Asp Pro260 265 270Ser Pro Asn Cys Lys Ile Ala Ser Asp Lys Asp Ala Lys Leu Thr Leu275 280 285Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser Leu Leu290 295 300Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Ser Thr Ala305 310 315 320Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Ala Leu Leu Glu Lys Ser325 330 335Thr Leu Asn Arg Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu Ile Pro340 345 350Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys Lys Ala355 360 365Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val Gly Glu370 375 380Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile Ile Thr385 390 395 400Phe Asn Glu Thr Asp Asp Glu Ser Cys Asp Tyr Cys Met Asn Phe Gln405 410 415Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala Thr Ser420 425 430Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 44021056211543212PRT213黑猩猩腺病毒-ChAd 17纖維40056Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Ile Thr Ser Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Ala Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ser Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp180 185 190Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile195 200 205Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val210 215220Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr Arg Val225 230 235240Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala245 250 255Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn290 295 300Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr305 310 315 320Lys Ile Ser Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile325 330 335Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Leu Thr Val340 345 350Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro355 360 365Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu370 375 380Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu385 390 395 400Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val405 410 415Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser420 425 430Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn435 440 445Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala450 455 460Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln465 470 475 480Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr485 490 495Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr500 505 510Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu515 520 525Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln530 535 540
21057211543212PRT213黑猩猩腺病毒-ChAd 19纖維40057Met Lys Arg Thr Lys Thr Ser Asp Lys Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Leu Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ala Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp180 185 190Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile195 200 205Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220Thr Gly Asn Gly Ile Ala Val Asp Asn Asn Ala Leu Gln Thr Arg Val225 230 235 240Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala245 250 255Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln275 280 285Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn290 295 300Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr305 310 315 320Lys Ile Gly Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile325 330 335Lys Leu Gly Thr Gly Val Ser Phe Asp Ser Thr Gly Ala Leu Ser Val340 345 350Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro355 360 365Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu370 375 380Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu385 390 395 400Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ser Ser Val405 410 415Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser420 425 430Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn435 440 445Ala Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala450 455 460Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln465 470 475 480Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr
485 490 495Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr500 505 510Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu515 520 525Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln530 535 54021058211963212DNA213黑猩猩腺病毒-ChAd 8纖維40058atgaccaaac gagttcgact aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60agcagctccc aacacccctt tataaaccct ggtttcattt cctcaaatgg atttacacaa 120agcccagatg gggttcttac acttaaatgc ttatcgccgc tcaccaccac aggcggctcc 180cttcaactta aagttggagg aggattatca gtggatgaca ctgacggttc attagaagaa 240aacataagca ttacagcacc acttaataaa acaagtcact caataggttt atccatagga 300gatgggttgg aaacaaaaaa caaccaacta tgtgctaagc tgggagacgg tcttacattt 360aatacaggca gcatatgcat agatactgac attaatacat tatggacagg agcaacacca 420gacgctaatt gcttagtcct tggaactgaa tctaatgatt gtaaacttac actggcactt 480gtaaagtcag gagccttagt aaatgcttac gtagcacttg ttggagcctc agacgccgtt 540aatgatttaa ccacagaaac aagtgctcaa ataattgcag acatatattt tgatgcgcaa 600ggaaaacttc ttcctgattt atcagcactc aaaacagagc taaaacacaa atctggacaa 660ggcacttcga cagcagatcc caataactgt aaaagcttta tgccaagtct aaatgcatat 720ccactgcgcc ccaatggagg caacggaaac tatatttatg gaaccaccta ctacagggcc 780agagatgaaa ccctttatga acttaaaacc tctgtaatgc ttaactacaa aattaccagt 840ggactatgtg catatgccat gcattttcag tggtcttgga atagtgggac taaaccagaa 900gacactcccg ccactttcat tgcctccccc tttgtctttt cctacattag agaagatgac 960tga 96321059211320
212PRT213黑猩猩腺病毒-ChAd 8纖維40059Met Thr Lys Arg Val Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe20 25 30Ile Ser Ser Asn Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu35 40 45Lys Cys Leu Ser Pro Leu Thr Thr Thr Gly Gly Ser Leu Gln Leu Lys50 55 60Val Gly Gly Gly Leu Ser Val Asp Asp Thr Asp Gly Ser Leu Glu Glu65 70 75 80Asn Ile Ser Ile Thr Ala Pro Leu Asn Lys Thr Ser His Ser Ile Gly85 90 95Leu Ser Ile Gly Asp Gly Leu Glu Thr Lys Asn Asn Gln Leu Cys Ala100 105 110Lys Leu Gly Asp Gly Leu Thr Phe Asn Thr Gly Ser Ile Cys Ile Asp115 120 125Thr Asp Ile Asn Thr Leu Trp Thr Gly Ala Thr Pro Asp Ala Asn Cys130 135 140Leu Val Leu Gly Thr Glu Ser Asn Asp Cys Lys Leu Thr Leu Ala Leu145 150 155 160Val Lys Ser Gly Ala Leu Val Asn Ala Tyr Val Ala Leu Val Gly Ala165 170 175Ser Asp Ala Val Asn Asp Leu Thr Thr Glu Thr Ser Ala Gln Ile Ile180 185 190Ala Asp Ile Tyr Phe Asp Ala Gln Gly Lys Leu Leu Pro Asp Leu Ser195 200 205Ala Leu Lys Thr Glu Leu Lys His Lys Ser Gly Gln Gly Thr Ser Thr210 215 220Ala Asp Pro Asn Asn Cys Lys Ser Phe Met Pro Ser Leu Asn Ala Tyr225 230 235 240Pro Leu Arg Pro Asn Gly Gly Asn Gly Asn Tyr Ile Tyr Gly Thr Thr
245 250 255Tyr Tyr Arg Ala Arg Asp Glu Thr Leu Tyr Glu Leu Lys Thr Ser Val260 265 270Met Leu Asn Tyr Lys Ile Thr Ser Gly Leu Cys Ala Tyr Ala Met His275 280 285Phe Gln Trp Ser Trp Asn Ser Gly Thr Lys Pro Glu Asp Thr Pro Ala290 295 300Thr Phe Ile Ala Ser Pro Phe Val Phe Ser Tyr Ile Arg Glu Asp Asp305 310 315 320210602111062212DNA213黑猩猩腺病毒-ChAd 22纖維40060atggccaaac gagctcggct aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60agcagctcac aacacccctt tataaaccct ggtttcattt cctcaaatgg ttttgcacaa 120agcccagatg gagttctaac tcttaaatgt gttaatccgc tcactaccgc cagcggaccc 180ctccaactta aagttggaag cagtcttaca gtagataata tcgatgggtc tttggaggaa 240aatataactg ccgcagcgcc actcactaaa actaaccact ccataggttt atcaatagga 300tctggcttgc aaacaaagga tgataaactt tgtttatcgc tgggagatgg gttggtaaca 360aaggatgata aactatgttt atcgctggga gatgggttaa taacaaaaga tgatacacta 420tgtgccaaac taggacatgg ccttgtgttt gactcttcca atgctatcac catagaaaac 480aacaccttgt ggacaggtgc aaaaccaagc gccaactgtg taattaaaga gggagaagat 540tccccagact gtaagctcac tttagttcta gtgaagaatg gaggactgat aaatggatac 600ataacattaa tgggagcctc agaatatact aacaccttgt ttaaaaacaa acaagttaca 660atcgatgtaa acctcgcatt tgataatact ggccaaatta tcacttacct atcatccctt 720aaaagtaacc tgaactttaa agacaaccaa aacatggcta ctggaaccat aaccagtgcc 780aaaggcttca tgcccagcac caccgcctat ccatttataa catacgccac tcagtcccta 840aatgaagatt acatttatgg agagtgttac tacaaatcta ccaatggaac tctctttcca 900ctaaaagtta ctgtcacact aaacagacgt atgtcagctt ctggaatggc ctatgctatg 960aatttttcat ggtctctaaa tgcagaggaa gccccggaaa ctaccgaagt cactctcatt 1020acctccccct tctttttttc ttatatcaga gaagatgact ga 1062
21061211353212PRT213黑猩猩腺病毒-ChAd 22纖維40061Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe20 25 30Ile Ser Ser Asn Gly Phe Ala Gln Ser Pro Asp Gly Val Leu Thr Leu35 40 45Lys Cys Val Asn Pro Leu Thr Thr Ala Ser Gly Pro Leu Gln Leu Lys50 55 60Val Gly Ser Ser Leu Thr Val Asp Asn Ile Asp Gly Ser Leu Glu Glu65 70 75 80Asn Ile Thr Ala Ala Ala Pro Leu Thr Lys Thr Asn His Ser Ile Gly85 90 95Leu Ser Ile Gly Ser Gly Leu Gln Thr Lys Asp Asp Lys Leu Cys Leu100 105 110Ser Leu Gly Asp Gly Leu Val Thr Lys Asp Asp Lys Leu Cys Leu Ser115 120 125Leu Gly Asp Gly Leu Ile Thr Lys Asp Asp Thr Leu Cys Ala Lys Leu130 135 140Gly His Gly Leu Val Phe Asp Ser Ser Asn Ala Ile Thr Ile Glu Asn145 150 155 160Asn Thr Leu Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile Lys165 170 175Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val Lys180 185 190Asn Gly Gly Leu Ile Asn Gly Tyr Ile Thr Leu Met Gly Ala Ser Glu195 200 205Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val Asn
210 215 220Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser Leu225 230 235 240Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly Thr245 250 255Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro Phe260 265 270Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly Glu275 280 285Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val Thr290 295 300Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala Met305 310 315 320Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr Glu325 330 335Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu Asp340 345 350Asp210622111686212DNA213黑猩猩腺病毒-ChAd 24纖維40062atgtcagatt cttgctcctg tccttccgca cccactatct tcatgttgtt gcagatgaag60cgcaccaaaa cgtctgacga gagcttcaac cccgtgtacc cctatgacac ggaaaacggt120cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagagagc180ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc240gccctgaaaa tgggaagtgg cctctccctg gacgacgccg gcaacctcac ctctcaagat300gtcaccacca ctacccctcc cctgaaaaaa accaagacca acctcagcct agaaacctca360gcccccctga ctgtgagcac ctcaggcgcc ctcaccctag cggccgccgc tcccctggcg420gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa480
ctcaccctgg ccaccaaggg ccccctgacc gtgtctgaag gcaaactggc cttgcagacc 540tcggccccac tgacggccgc tgacagcagc accctcaccg ttagcgccac accacccatc 600aatgtaagca gtggaagttt gggcttagac atggaaaatc ccatgtatac tcatgacgga 660aaactgggaa taagaattgg gggcccactg agagtagtag acagcctgca cacactgact 720gtagttaccg gaaatggaat agctgtagat aacaatgccc tccaaactag agttacgggc 780gccctgggtt atgacacatc aggaaaccta caactgagag ccgcgggggg tatgcgaatt 840gatgcaaatg gccaacttat ccttgatgtg gcatacccat ttgatgctca aaacaatctc 900agccttagac ttggtcaggg acccctgtat gtaaacacag accacaacct agatttgaat 960tgcaacagag gtctgaccac aactaccacc aacaacacaa aaaaacttga aactaaaatt 1020ggctcaggct tagactatga taccaatggt gctgtcatta ttaaacttgg cactggtgtc 1080agctttgaca gcacaggcgc cctaagtgtg ggaaacactg gcgatgataa actgactctg 1140tggacaaccc cagacccatc tccaaattgc agaattcact cagacaaaga ctgcaagttt 1200actctagtcc taactaagtg tggaagtcac atcctggctt ctgtcgccgc cctagcggtg 1260tcaggaaatc tggcttcaat aacaggcacc gtttccagcg ttaccatctt tctcagattt 1320gatcagaatg gagtgcttat ggaaaactcc tcgctagaca agcagtactg gaactttaga 1380aatggtaatt caaccaatgc caccccctac accaatgcag ttggtttcat gccaaacctc 1440gcagcatacc ccaagacaca gagtcagact gctaaaaaca acattgtaag tcaggtttac 1500ttgaatgggg acaaatccaa acccatgatc cttaccatta ccctcaatgg aactaatgaa 1560tccagtgaaa ctagccaggt gagtcactac tccatgtcat ttacgtgggc ttgggagagt 1620gggcaatatg ccaccgaaac ctttgccacc aattccttta ccttctctta cattgctgaa 1680caataa 168621063211543212PRT213黑猩猩腺病毒-ChAd 24纖維40063Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Leu Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ala Thr Pro Pro Ile Asn Val Ser Ser Gly Ser Leu Gly Leu Asp180 185 190Met Glu Asn Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile195 200 205Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val210 215 220Thr Gly Asn Gly Ile Ala Val Asp Asn Asn Ala Leu Gln Thr Arg Val225 230 235 240Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala245 250 255Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln275280 285Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn290 295 300Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr305 310 315 320Lys Ile Gly Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335Lys Leu Gly Thr Gly Val Ser Phe Asp Ser Thr Gly Ala Leu Ser Val340 345 350Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro355 360 365Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu370 375 380Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu385 390 395 400Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ser Ser Val405 410 415Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser420 425 430Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn435 440 445Ala Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala450 455 460Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln465 470 475 480Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Ile Leu Thr Ile Thr485 490 495Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr500 505 510Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu515 520 525Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln530 535 540210642111335212DNA213黑猩猩腺病毒-ChAd 26纖維
40064atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgct gtccctgcgt ctggccgatc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agatggggtg gacctcgacg actcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcaaatccta 900ggcactgtct ccctattagc agtcagtggc agcttggctc ctatcacagg ggctgttaga 960actgcacttg tatcactcaa attcaatgct aatggagccc ttttggacaa atcaactctg 1020aacaaagaat actggaacta cagacaagga gatctaattc caggtacacc atatacacat 1080gctgtgggtt tcatgcctaa caaaaaagcc taccctaaaa acacaactgc agcttccaag 1140agccacattg tgggtgatgt gtatttagat ggagatgcag ataaaccttt atctcttatc 1200atcactttca atgaaactga tgatgaaacc tgtgattact gcatcaactt tcaatggaaa 1260tggggagctg atcaatataa ggataagaca ctcgcaacca gttcattcac cttctcatac 1320atcgcccaag aataa 133521065211444212PRT213黑猩猩腺病毒-ChAd 26纖維40065Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Asp Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu100 105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115 120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn130 135 140Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala145 150 155 160Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala165 170175Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe195 200 205Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln210 215 220Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu225 230 235 240Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu275 280 285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295 300Leu Leu Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Arg
305 310 315 320Thr Ala Leu Val Ser Leu Lys Phe Asn Ala Asn Gly Ala Leu Leu Asp325 330 335Lys Ser Thr Leu Asn Lys Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu340 345 350Ile Pro Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys355 360 365Lys Ala Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val370 375 380Gly Asp Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile385 390 395 400Ile Thr Phe Asn Glu Thr Asp Asp Glu Thr Cys Asp Tyr Cys Ile Asn405 410 415Phe Gln Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala420 425 430Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 440210662111062212DNA213黑猩猩腺病毒-ChAd 30纖維40066atggccaaac gagctcggct aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60agcagctcac aacacccctt tataaaccct ggtttcattt cctcaaatgg ttttgcacaa 120agcccagatg gagttctaac tcttaaatgt gttaatccgc tcactaccgc cagcggaccc 180ctccaactta aagttggaag cagtcttaca gtagatacta tcgatgggtc tttggaggaa 240aatataactg ccgcagcgcc actcactaaa actaaccact ccataggttt atcaatagga 300tctggcttgc aaacaaagga tgataaactt tgtttatcgc tgggagatgg gttggtaaca 360aaggatgata aactatgttt atcgctggga gatgggttaa taacaaaaga tgatacacta 420tgtgccaaac taggacatgg ccttgtgttt gactcttcca atgctatcac catagaaaac 480aacaccttgt ggacaggtgc aaaaccaagc gccaactgtg taattaaaga gggagaagat 540
tccccagact gtaagctcac tttagttcta gtgaagaatg gaggactgat aaatggatac 600ataacattaa tgggagcctc agaatatact aacaccttgt ttaaaaacaa acaagttaca 660atcgatgtaa acctcgcatt tgataatact ggccaaatta tcacttacct atcatccctt 720aaaagtaacc tgaactttaa agacaaccaa aacatggcta ctggaaccat aaccagtgcc 780aaaggcttca tgcccagcac caccgcctat ccatttataa catacgccac tcagtcccta 840aatgaagatt acatttatgg agagtgttac tacaaatcta ccaatggaac tctctttcca 900ctaaaagtta ctgtcacact aaacagacgt atgtcagctt ctggaatggc ctatgctatg 960aatttttcat ggtctctaaa tgcagaggaa gccccggaaa ctaccgaagt cactctcatt 1020acctccccct tctttttttc ttatatcaga gaagatgact ga 106221067211353212PRT213黑猩猩腺病毒-ChAd 30纖維40067Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe20 25 30Ile Ser Ser Asn Gly Phe Ala Gln Ser Pro Asp Gly Val Leu Thr Leu35 40 45Lys Cys Val Asn Pro Leu Thr Thr Ala Ser Gly Pro Leu Gln Leu Lys50 55 60Val Gly Ser Ser Leu Thr Val Asp Thr Ile Asp Gly Ser Leu Glu Glu65 70 75 80Asn Ile Thr Ala Ala Ala Pro Leu Thr Lys Thr Asn His Ser Ile Gly85 90 95Leu Ser Ile Gly Ser Gly Leu Gln Thr Lys Asp Asp Lys Leu Cys Leu100 105 110Ser Leu Gly Asp Gly Leu Val Thr Lys Asp Asp Lys Leu Cys Leu Ser115 120 125Leu Gly Asp Gly Leu Ile Thr Lys Asp Asp Thr Leu Cys Ala Lys Leu130 135 140Gly His Gly Leu Val Phe Asp Ser Ser Asn Ala Ile Thr Ile Glu Asn145 150 155 160
Asn Thr Lau Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile Lys165 170 175Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val Lys180 185 190Asn Gly Gly Leu Ile Asn Gly Tyr Ile Thr Leu Met Gly Ala Ser Glu195 200 205Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val Asn210 215 220Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser Leu225 230 235 240Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly Thr245 250 255Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro Phe260 265 270Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly Glu275 280 285Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val Thr290 295 300Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala Met305 310 315 320Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr Glu325 330 335Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu Asp340 345 350Asp210682111791212DNA213黑猩猩腺病毒-ChAd 31纖維40068atgtcagatt cttgctcctg tccctccgca cccactatct tcatgttgtt gcagatgaag60cgcaccaaaa cgtctgacga gagcttcaac cccgtgtacc cctatgacac ggaaagcggc120
cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagaaagt180ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc240gccctgaaaa tgggaagtgg cctctccctg gacgacgctg gcaacctcac ctctcaagat300atcaccaccg ctagccctcc cctcaaaaaa accaagacca acctcagcct agaaacctca360tcccccctaa ctgtgagcac ctcaggcgcc ctcaccgtag cagccgccgc tcccctggcg420gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa480ctcaccctgg ccaccaaagg ccccctgacc gtgtctgaag gcaaactggc cttgcaaaca540tcggccccgc tgacggccgc tgacagcagc accctcacag tcagtgccac accacccctt600agcacaagca atggcagctt gggtattgac atgcaagccc ccatttacac caccaatgga660aaactaggac ttaactttgg cgctcccctg catgtggtag acagcctaaa tgcactgact720gtagttactg gccaaggtct tacgataaac ggaacagccc tacaaactag agtctcaggt780gccctcaact atgacacatc aggaaaccta gaattgagag ctgcaggggg tatgcgagtt840gatgcaaatg gtcaacttat ccttgatgta gcttacccat ttgatgcaca aaacaatctc900agccttaggc ttggacaggg acccctgttt gttaactctg cccacaactt ggatgttaac960tacaacagag gcctctacct gttcacatct ggaaatacca aaaagctaga agttaatatc1020aaaacagcca agggtctcat ttatgatgac actgctatag caatcaatgc gggtgatggg1080ctacagtttg actcaggctc agatacaaat ccattaaaaa ctaaacttgg attaggactg1140gattatgact ccagcagagc cataattgct aaactgggaa ctggcctaag ctttgacaac1200acaggtgcca tcacagtagg caacaaaaat gatgacaagc ttaccttgtg gaccacacca1260gacccatccc ctaactgtag aatctattca gagaaagatg ctaaattcac acttgttttg1320actaaatgcg gcagtcaggt gttggccagc gtttctgttt tatctgtaaa aggtagcctt1380gcgcccatca gtggcacagt aactagtgct cagattgtcc tcagatttga tgaaaatgga1440gttctactaa gcaattcttc ccttgaccct caatactgga actacagaaa aggtgacctt1500acagagggca ctgcatatac caacgcagtg ggatttatgc ccaacctcac agcataccca1560aaaacacaga gccaaactgc taaaagcaac attgtaagtc aggtttactt gaatggggac1620aaatccaaac ccatgaccct caccattacc ctcaatggaa ctaatgaaac aggagatgcc1680acagtaagca cttactccat gtcattctca tggaactgga atggaagtaa ttacattaat1740gaaacgttcc aaaccaactc cttcaccttc tcctacatcg cccaagaata a 179121069211578212PRT213黑猩猩腺病毒-ChAd 31纖維40069
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp180 185 190Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe195 200 205Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val210 215 220Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val225 230 235 240Ser Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu Arg Ala245 250 255Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu Asp Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn290 295 300Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val305 310 315 320Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala325 330 335Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp Ser Gly Ser Asp Thr Asn340 345 350Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Asp Tyr Asp Ser Ser Arg355 360 365Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly370 375 380Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr385 390 395 400Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala405 410 415Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser420 425 430Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr435 440 445Val Thr Ser Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly Val Leu450 455 460Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly465 470 475 480Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro485 490 495Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn500 505 510Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr515 520 525Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val530 535 540Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr
545 550 555 560Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala565 570 575Gln Glu21070211978212DNA213黑猩猩腺病毒-ChAd 37纖維40070atggccaaac gggctcgtct aagcagctcc ttcaacccgg tgtaccccta tgaagacgag 60agcagctcac aacacccatt tataaacccc ggcttcattt cccctgatgg ctttacacaa 120agcccagacg gagttctaac actgaaatgt gtttcccctc ttactaccac cagtggcgct 180ctagacatta aagtgggaag agggcttaaa gtagatagca ctgatggttc cctggaagaa 240aatatagaca ttacagctcc cctcactaaa tttaaccact cagtaggatt agcatttggc 300gacggtctag aaacaaaaga aaacaagctt tatgtaaaac ttggagatgg acttaaattt 360agctctggca gtatatacat tgaccatgat gttaacactt tatggacagg agtcaatcca 420agtgctaact gtataattac agacaatgga gaaaccaatg acagcaagct taccctaata 480cttgttaagt caggtggatt aataaatgct tatgtctcat taatgggtga ctcagacaca 540gtcaataaat taaccacaga aaaaagtgct caaattaccg ttgacatata ctttgataat 600caaggaaaag ttcttactga actatcggcc cttaaaacag atcttaaaca taaatttggt 660caaaacatgg cttctagcga agtatcaaac tgcaaaggct ttatgccaag cttaaatgca 720tacccattca gaaatccaac taaacctacc aaaggaagag aagactacat ttatggaata 780acttactatc aagccacaga tggtaatctc tatgagctaa aaactactat tactctaaac 840cacagtgtca ttagttctct atgtgcatat gcaatgcaca tttcatggtc atgggacacc 900gtaacagagc cagagacaac acccactact cttattacct cccccttctc cttttcctat 960atcagagaag atgactga97821071211325212PRT213黑猩猩腺病毒-ChAd 37纖維
40071Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe20 25 30Ile Ser Pro Asp Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu35 40 45Lys Cys Val Ser Pro Leu Thr Thr Thr Ser Gly Ala Leu Asp Ile Lys50 55 60Val Gly Arg Gly Leu Lys Val Asp Ser Thr Asp Gly Ser Leu Glu Glu65 70 75 80Asn Ile Asp Ile Thr Ala Pro Leu Thr Lys Phe Asn His Ser Val Gly85 90 95Leu Ala Phe Gly Asp Gly Leu Glu Thr Lys Glu Asn Lys Leu Tyr Val100 105 110Lys Leu Gly Asp Gly Leu Lys Phe Ser Ser Gly Ser Ile Tyr Ile Asp115 120 125His Asp Val Asn Thr Leu Trp Thr Gly Val Asn Pro Ser Ala Asn Cys130 135 140Ile Ile Thr Asp Asn Gly Glu Thr Asn Asp Ser Lys Leu Thr Leu Ile145 150 155 160Leu Val Lys Ser Gly Gly Leu Ile Asn Ala Tyr Val Ser Leu Met Gly165 170 175Asp Ser Asp Thr Val Asn Lys Leu Thr Thr Glu Lys Ser Ala Gln Ile180 185 190Thr Val Asp Ile Tyr Phe Asp Asn Gln Gly Lys Val Leu Thr Glu Leu195 200 205Ser Ala Leu Lys Thr Asp Leu Lys His Lys Phe Gly Gln Asn Met Ala210 215 220Ser Ser Glu Val Ser Asn Cys Lys Gly Phe Met Pro Ser Leu An Ala225 230 235240Tyr Pro Phe Arg Asn Pro Thr Lys Pro Thr Lys Gly Arg Glu Asp Tyr245 250 255Ile Tyr Gly Ile Thr Tyr Tyr Gln Ala Thr Asp Gly Asn Leu Tyr Glu
260 265 270Leu Lys Thr Thr Ile Thr Leu Asn His Ser Val Ile Ser Ser Leu Cys275 280 285Ala Tyr Ala Met His Ile Ser Trp Ser Trp Asp Thr Val Thr Glu Pro290 295 300Glu Thr Thr Pro Thr Thr Leu Ile Thr Ser Pro Phe Ser Phe Ser Tyr305 310 315 320Ile Arg Glu Asp Asp325210722111332212DNA213黑猩猩腺病毒-ChAd 38纖維40072atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggataccc ctttttatac caaagatgga aaattatcct tacaagtttc tccaccatta 360aacatattaa aatcaaccat tctgaacaca ttagctgtag cttatggatc aggtttagga 420ctcagtggtg gcactgctct tgcagtacag ttggcctctc cactcacctt tgatgaaaaa 480ggaaatatta aaattaacct agccagtggt ccattaacag ttgatgcaag tcgacttagt 540atcaactgca aaagaggggt cactgtcact accgcaggag atgcaattaa aagcaacata 600agctggccta aaggtataag atttgaaggt gatgccatag ctgcaaacat tggcagagga 660ttggaatttg gaaccactag tacagagact gatgtcacag atgcataccc aattcaagtt 720aaattgggta ctggtctcac ctttgacagt acaggcgcca ttgttgcatg gaacaaagag 780gatgataaac ttacattatg gaccacagcc gacccctcgc caaattgcaa aatatactct 840gaaaaagatg ctaaactcac actttgcttg acaaaatgtg gaagccaaat tctgggcact 900gtgactgtat tggcagtgaa taatggaagt ctcaacccaa tcacaaacac agtaagcact 960gcacttgtct ccctcaagtt tgatgcaagt ggagttttgc taagcagctc cacattagac 1020aaagaatatt ggaacttccg aaagggagat gttacacctg ctgaacccta tactaatgct 1080
ataggtttta tgcctaacat aaaggcctat cctaaaaaca catctgcagc ttcaaaaagc 1140catattgtca gtcaagttta tctcaatggg gatgaaacca aacctctgat gctgattatt 1200acttttaatg aaactgagga tgcaacttgc acctatagta tcacttttca atggaaatgg 1260gatagtacta agtacacagg taaaacactt gctaccagct ccttcacctt ctcctacatt 1320gctcaagaat ga 133221073211443212PRT213黑猩猩腺病毒-ChAd 38纖維40073Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Lys Ser Thr Ile Leu115 120 125Asn Thr Leu Ala Val Ala Tyr Gly Ser Gly Leu Gly Leu Ser Gly Gly130 135 140Thr Ala Leu Ala Val Gln Leu Ala Ser Pro Leu Thr Phe Asp Glu Lys145 150 155 160Gly Asn Ile Lys Ile Asn Leu Ala Ser Gly Pro Leu Thr Val Asp Ala165 170 175Ser Arg Leu Ser Ile Asn Cys Lys Arg Gly Val Thr Val Thr Thr Ala
180 185 190Gly Asp Ala Ile Lys Ser Asn Ile Ser Trp Pro Lys Gly Ile Arg Phe195 200 205Glu Gly Asp Ala Ile Ala Ala Asn Ile Gly Arg Gly Leu Glu Phe Gly210 215 220Thr Thr Ser Thr Glu Thr Asp Val Thr Asp Ala Tyr Pro Ile Gln Val225 230 235 240Lys Leu Gly Thr Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile Val Ala245 250 255Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala Asp Pro260 265 270Ser Pro Asn Cys Lys Ile Tyr Ser Glu Lys Asp Ala Lys Leu Thr Leu275 280 285Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Thr Val Leu290 295 300Ala Val Asn Asn Gly Ser Leu Asn Pro Ile Thr Asn Thr Val Ser Thr305 310 315 320Ala Leu Val Ser Leu Lys Phe Asp Ala Ser Gly Val Leu Leu Ser Ser325 330 335Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp Val Thr340 345 350Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn Ile Lys355 360 365Ala Tyr Pro Lys Asn Thr Ser Ala Ala Ser Lys Ser His Ile Val Ser370 375 380Gln Val Tyr Leu Asn Gly Asp Glu Thr Lys Pro Leu Met Leu Ile Ile385 390 395 400Thr Phe Asn Glu Thr Glu Asp Ala Thr Cys Thr Tyr Ser Ile Thr Phe405 410 415Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Lys Thr Leu Ala Thr420 425 430Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 440
210742111332212DNA213黑猩猩腺病毒-ChAd 44纖維40074atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgtt gtccctgcga ctggctgacc ccgtcaccac caagaacggg 180gaaatcaccc tcaagctggg agagggggtg gacctcgact cgtcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtatttcaa acaacaccat ttcccttaaa 300actgctgccc ctttctacaa caacaatgga actttaagcc tcaatgtctc cacaccatta 360gcagtatttc ccacatttaa cactttaggc ataagtcttg gaaacggtct tcagacttca 420aataagttgt tgactgtaca actaactcat cctcttacat tcagctcaaa tagcatcaca 480gtaaaaacag acaaagggct atatattaac tccagtggaa acagaggact tgaggctaat 540ataagcctaa aaagaggact agtttttgac ggtaatgcta ttgcaacata tattggaaat 600ggcttagact atggatctta tgatagtgat ggaaaaacaa gacccgtaat taccaaaatt 660ggagcaggat taaattttga tgctaacaaa gcaatagctg tcaaactagg cacaggttta 720agttttgact ccgctggtgc cttgacagct ggaaacaaac aggatgacaa gctaacactt 780tggactaccc ctgacccaag ccctaattgt caattacttt cagacagaga tgccaaattt 840actctctgtc ttacaaaatg cggtagtcaa atactaggca ctgtggcagt ggcggctgtt 900actgtaggat cagcactaaa tccaattaat gacacagtca aaagcgccat agttttcctt 960agatttgatt ccgatggtgt actcatgtca aactcatcaa tggtaggtga ttactggaac 1020tttagggagg gacagaccac tcaaagtgta gcctatacaa atgctgtggg attcatgcca 1080aatataggtg catatccaaa aacccaaagt aaaacaccta aaaatagcat agtcagtcag 1140gtatatttaa ctggagaaac tactatgcca atgacactaa ccataacttt caatggcact 1200gatgaaaaag acacaacccc agttagcacc tactctatga cttttacatg gcagtggact 1260ggagactata aggacaaaaa tattaccttt gctaccaact cattctcttt ttcctacatc 1320gcccaggaat aa 133221075211443212PRT213黑猩猩腺病毒-ChAd 44纖維
40075Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Ile Ser Asn Asn Thr85 90 95Ile Ser Leu Lys Thr Ala Ala Pro Phe Tyr Asn Asn Asn Gly Thr Leu100 105 110Ser Leu Asn Val Ser Thr Pro Leu Ala Val Phe Pro Thr Phe Asn Thr115 120 125Leu Gly Ile Ser Leu Gly Asn Gly Leu Gln Thr Ser Asn Lys Leu Leu130 135 140Thr Val Gln Leu Thr His Pro Leu Thr Phe Ser Ser Asn Ser Ile Thr145 150 155 160Val Lys Thr Asp Lys Gly Leu Tyr Ile Asn Ser Ser Gly Asn Arg Gly165 170 175Leu Glu Ala Asn Ile Ser Leu Lys Arg Gly Leu Val Phe Asp Gly Asn180 185 190Ala Ile Ala Thr Tyr Ile Gly Asn Gly Leu Asp Tyr Gly Ser Tyr Asp195 200 205Ser Asp Gly Lys Thr Arg Pro Val Ile Thr Lys Ile Gly Ala Gly Leu210 215 220Asn Phe Asp Ala Asn Lys Ala Ile Ala Val Lys Leu Gly Thr Gly Leu225 230 235 240Ser Phe Asp Ser Ala Gly Ala Leu Thr Ala Gly Asn Lys Gln Asp Asp245 250 255Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Gln Leu
260 265 270Leu Ser Asp Arg Asp Ala Lys Phe Thr Leu Cys Leu Thr Lys Cys Gly275 280 285Ser Gln Ile Leu Gly Thr Val Ala Val Ala Ala Val Thr Val Gly Ser290 295 300Ala Leu Asn Pro Ile Asn Asp Thr Val Lys Ser Ala Ile Val Phe Leu305 310 315 320Arg Phe Asp Ser Asp Gly Val Leu Met Ser Asn Ser Ser Met Val Gly325 330 335Asp Tyr Trp Asn Phe Arg Glu Gly Gln Thr Thr Gln Ser Val Ala Tyr340 345 350Thr Asn Ala Val Gly Phe Met Pro Asn Ile Gly Ala Tyr Pro Lys Thr355 360 365Gln Ser Lys Thr Pro Lys Asn Ser Ile Val Ser Gln Val Tyr Leu Thr370 375 380Gly Glu Thr Thr Met Pro Met Thr Leu Thr Ile Thr Phe Asn Gly Thr385 390 395 400Asp Glu Lys Asp Thr Thr Pro Val Ser Thr Tyr Ser Met Thr Phe Thr405 410 415Trp Gln Trp Thr Gly Asp Tyr Lys Asp Lys Asn Ile Thr Phe Ala Thr420 425 430Asn Ser Phe Ser Phe Ser Tyr Ile Ala Gln Glu435 440210762111278212DNA213黑猩猩腺病毒-ChAd 63纖維40076atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720aaagaagacg ataaactcac tttgtggaca acacctgatc catcgccaaa ctgtcaaata 780ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260tacatcgccc aagaatga 127821077211425212PRT213黑猩猩腺病毒-ChAd 63纖維40077Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu115 120 125Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser130 135 140Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly145 150 155 160Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp165 170 175Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp180 185190Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser195 200 205Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu210 215 220Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn225 230 235 240Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro245 250 255Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu260 265 270Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val275 280 285Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln290 295 300Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser305 310 315 320Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly325 330 335Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val355 360 365Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu370 375 380Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr385 390 395 400Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser405 410 415Tyr Thr Phe Ser Tyr Ile Ala Gln Glu420 425210782111338212DNA213黑猩猩腺病毒-ChAd 82纖維40078atgtccaaaa agcgcgcgcg ggtggatgat gacttcgacc ccgtgtaccc ctacgatgca 60gacaacgcac cgactgtgcc cttcatcaac cctcccttcg tctcttcaga tggattccaa 120gaaaagcccc tgggggtgtt gtccctgcga ctggccgatc ccgtcaccac caagaacggg 180gctgtcaccc tcaagctggg ggagggggtg gacctcgacg actcgggaaa actcatctcc 240aaaaatgcca ccaaggccac tgcccctctc agtatttcca acaacaccat ttcccttaac 300atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcagatactg 900ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggaaaagta 960
accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaagc cagttcaaca 1020ctagataaag aatattggaa tttcagaaaa ggagatgtga cacctgctga cccctacact 1080aatgctatag gctttatgcc caaccttaat gcatacccaa aaaacacaaa cgcagctgca 1140aaaagtcaca ttgttggaaa agtataccta catggggatg taagcaagcc actagacttg 1200ataattacat ttaatgaaac cagtgatgaa tcctgtactt attgcattaa ctttcagtgg 1260cggtggggaa ctgaccaata taaagatgaa acacttgcag tcagttcatt caccttctca 1320tacattgcta aagaataa133821079211445212PRT213黑猩猩腺病毒-ChAd 82纖維40079Met Ser Lys Lys Arg Ala Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Ala Val Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Asp Ser Gly Lys Lau Ile Ser65 70 75 80Lys Asn Ala Thr Lys Ala Thr Ala Pro Leu Ser Ile Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu100 105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115 120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn130 135 140Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala145 150 155 160Ser Lys Ile Ala Leu Asn Lau Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe195 200 205Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln210 215 220Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu225 230 235 240Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu275 280 285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295 300Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Lys Val305 310 315 320Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln325 330 335Ala Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp340 345 350Val Thr Pro Ala Asp Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn355 360 365Leu Asn Ala Tyr Pro Lys Asn Thr Asn Ala Ala Ala Lys Ser His Ile370 375 380Val Gly Lys Val Tyr Leu His Gly Asp Val Ser Lys Pro Leu Asp Leu385 390 395 400Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile405 410 415Asn Phe Gln Trp Arg Trp Gly Thr Asp Gln Tyr Lys Asp Glu Thr Leu420 425 430Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu
435 440 44521080211445212PRT213黑猩猩腺病毒-CV23/Pan5纖維40080Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Asp Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Asn Asn Asn Gly Lys Leu100 105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115 120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Thr130 135 140Gly Ala Leu Val Ala Gln Leu Ala Ser Pro Leu Ala Phe Asp Ser Asn145 150 155 160Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala165 170 175Asn Arg Leu Asn Ile Asn Cys Asn Arg Gly Leu Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Ala Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205Ile Gly Asn Ala Met Gly Val Asn Ile Asp Thr Gln Lys Gly Leu Gln210 215 220Phe Gly Thr Thr Ser Thr Val Ala Asp Val Lys Asn Ala Tyr Pro Ile225 230 235 240Gln Ile Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Asp Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Glu Lys Asp Ala Lys Leu275 280 285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295 300Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Thr Val305 310 315 320Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln325 330 335Ser Ser Ser Thr Leu Asp Ser Asp Tyr Trp Asn Phe Arg Gln Gly Asp340 345 350Val Thr Pro Ala Glu Ala Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn355 360 365Leu Lys Ala Tyr Pro Lys Asn Thr Ser Gly Ala Ala Lys Ser His Ile370 375 380Val Gly Lys Val Tyr Leu His Gly Asp Thr Gly Lys Pro Leu Asp Leu385 390 395 400Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile405 410 415Asn Phe Gln Trp Gln Trp Gly Ala Asp Gln Tyr Lys Asn Glu Thr Leu420 425 430Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu435 440 44521081
2ll443212PRT213黑猩猩腺病毒-CV32/Pan6纖維400 81Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Ile Ser Asn Asn Thr85 90 95Ile Ser Leu Lys Thr Ala Ala Pro Phe Tyr Asn Asn Asn Gly Thr Leu100 105 110Ser Leu Asn Val Ser Thr Pro Leu Ala Val Phe Pro Thr Phe Asn Thr115 120 125Leu Gly Ile Ser Leu Gly Asn Gly Leu Gln Thr Ser Asn Lys Leu Leu130 135140Thr Val Gln Leu Thr His Pro Leu Thr Phe Ser Ser Asn Ser Ile Thr145 150 155 160Val Lys Thr Asp Lys Gly Leu Tyr Ile Asn Ser Ser Gly Asn Arg Gly165 170 175Leu Glu Ala Asn Ile Ser Leu Lys Arg Gly Leu Val Phe Asp Gly Asn180 185 190Ala Ile Ala Thr Tyr Ile Gly Asn Gly Leu Asp Tyr Gly Ser Tyr Asp195 200 205Ser Asp Gly Lys Thr Arg Pro Val Ile Thr Lys Ile Gly Ala Gly Leu210 215 220Asn Phe Asp Ala Asn Lys Ala Ile Ala Val Lys Leu Gly Thr Gly Leu
225 230 235 240Ser Phe Asp Ser Ala Gly Ala Leu Thr Ala Gly Asn Lys Gln Asp Asp245 250 255Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Gln Leu260 265 270Leu Ser Asp Arg Asp Ala Lys Phe Thr Leu Cys Leu Thr Lys Cys Gly275 280 285Ser Gln Ile Leu Gly Thr Val Ala Val Ala Ala Val Thr Val Gly Ser290 295 300Ala Leu Asn Pro Ile Asn Asp Thr Val Lys Ser Ala Ile Val Phe Leu305 310 315 320Arg Phe Asp Ser Asp Gly Val Leu Met Ser Asn Ser Ser Met Val Gly325 330 335Asp Tyr Trp Asn Phe Arg Glu Gly Gln Thr Thr Gln Ser Val Ala Tyr340 345 350Thr Asn Ala Val Gly Phe Met Pro Asn Ile Gly Ala Tyr Pro Lys Thr355 360 365Gln Ser Lys Thr Pro Lys Asn Ser Ile Val Ser Gln Val Tyr Leu Thr370 375 380Gly Glu Thr Thr Met Pro Met Thr Leu Thr Ile Thr Phe Asn Gly Thr385 390 395 400Asp Glu Lys Asp Thr Thr Pro Val Ser Thr Tyr Ser Met Thr Phe Thr405 410 415Trp Gln Trp Thr Gly Asp Tyr Lys Asp Lys Asn Ile Thr Phe Ala Thr420 425 430Asn Ser Phe Ser Phe Ser Tyr Ile Ala Gln Glu435 44021082211443212PRT213黑猩猩腺病毒-CV33/Pan7纖維
40082Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Thr Lys Asp Gly Lys Leu100 105 110Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Lys Ser Thr Ile Leu115 120 125Asn Thr Leu Ala Val Ala Tyr Gly Ser Gly Leu Gly Leu Ser Gly Gly130 135 140Thr Ala Leu Ala Val Gln Leu Ala Ser Pro Leu Thr Phe Asp Glu Lys145 150 155 160Gly Asn Ile Lys Ile Asn Leu Ala Ser Gly Pro Leu Thr Val Asp Ala165 170 175Ser Arg Leu Ser Ile Asn Cys Lys Arg Gly Val Thr Val Thr Thr Ser180 185 190Gly Asp Ala Ile Glu Ser Asn Ile Ser Trp Pro Lys Gly Ile Arg Phe195 200 205Glu Gly Asn Gly Ile Ala Ala Asn Ile Gly Arg Gly Leu Glu Phe Gly210 215 220Thr Thr Ser Thr Glu Thr Asp Val Thr Asp Ala Tyr Pro Ile Gln Val225 230 235 240Lys Leu Gly Thr Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile Val Ala245 250 255Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala Asp Pro
260 265 270Ser Pro Asn Cys Lys Ile Tyr Ser Glu Lys Asp Ala Lys Leu Thr Leu275 280 285Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Thr Val Leu290 295 300Ala Val Asn Asn Gly Ser Leu Asn Pro Ile Thr Asn Thr Val Ser Thr305 310 315 320Ala Leu Val Ser Leu Lys Phe Asp Ala Ser Gly Val Leu Leu Ser Ser325 330 335Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp Val Thr340 345 350Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn Ile Lys355 360 365Ala Tyr Pro Lys Asn Thr Ser Ala Ala Ser Lys Ser His Ile Val Ser370 375 380Gln Val Tyr Leu Asn Gly Asp Glu Ala Lys Pro Leu Met Leu Ile Ile385 390 395 400Thr Phe Asn Glu Thr Glu Asp Ala Thr Cys Thr Tyr Ser Ile Thr Phe405 410 415Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Glu Thr Leu Ala Thr420 425 430Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu435 44021083211543212PRT213黑猩猩腺病毒-ChAd 3纖維40083Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser35 40 45Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu50 55 60Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser65 70 75 80Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn85 90 95Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala100 105 110Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu115 120 125Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr130 135 140Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu145 150 155 160Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val165 170 175Ser Ala Thr Pro Pro Ile Asn Val Ser Ser Gly Ser Leu Gly Leu Asp180 185190Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile195 200 205Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val210 215 220Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr Arg Val225 230 235 240Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala245 250 255Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asn Val260 265 270Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln275 280 285Gly Pro Leu Tyr Ile Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr305 310 315 320Lys Ile Ser Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile325 330 335Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Leu Thr Val340 345 350Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro355 360 365Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu370 375 380Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu385 390 395 400Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val405 410 415Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser420 425 430Ser Leu Asp Arg Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn435 440 445Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala450 455 460Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln465 470 475 480Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr485 490 495Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr500 505 510Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu515 520 525Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln530 535 54021084
211445212PRT213黑猩猩腺病毒-ChAd 6纖維40084Met Ser Lys Lys Arg Ala Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Ala Val Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser65 70 75 80Lys Asn Ala Thr Lys Ala Thr Ala Pro Leu Ser Ile Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu100 105 110Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu115 120 125Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn130 135 140Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala145 150 155 160Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala165 170 175Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr180 185 190Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe195 200 205Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln210 215 220Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu
225 230 235 240Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile245 250 255Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala260 265 270Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu275 280 285Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser290 295 300Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Lys Val305 310 315 320Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln325 330 335Ala Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp340 345 350Val Thr Pro Ala Asp Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn355 360 365Leu Asn Ala Tyr Pro Lys Asn Thr Asn Ala Ala Ala Lys Ser His Ile370 375 380Val Gly Lys Val Tyr Leu His Gly Asp Glu Ser Lys Pro Leu Asp Leu385 390 395 400Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile405 410 415Asn Phe Gln Trp Gln Trp Gly Thr Asp Gln Tyr Lys Asp Glu Thr Leu420 425 430Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu435 440 44521085211322212PRT213黑猩猩腺病毒-C1纖維
40085Met Ala Lys Arg Thr Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro1 5 10 15Tyr Glu Asp Glu Asn Ser Ser His Pro Phe Ile Asn Pro Gly Phe Ile20 25 30Ser Pro Asn Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu Asn35 40 45Cys Val Ala Pro Leu Thr Thr Ala Asn Gly Ala Leu Asp Ile Lys Val50 55 60Gly Gly Gly Leu Lys Val Asn Ser Thr Asp Gly Phe Leu Glu Glu Asn65 70 75 80Ile Asn Ile Thr Ser Pro Leu Thr Lys Ser Asn His Ser Ile Gly Leu85 90 95Glu Trp Ser Asp Gly Leu Gln Thr Asn Glu Ala Lys Leu Cys Val Lys100 105 110Leu Gly Lys Gly Leu Val Phe Asp Ser Ser Ser Ala Ile Ala Met Glu115 120 125Asn Asn Thr Leu Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile130 135 140Lys Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val145 150 155 160Lys Asn Gly Gly Leu Val Asn Gly Tyr Ile Thr Len Met Gly Asp Ser165 170 175Glu Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val180 185 190Asn Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser195 200 205Leu Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly210 215 220Thr Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro225 230 235 240Phe Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly245 250 255Glu Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val
260 265 270Thr Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala275 280 285Met Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr290 295 300Glu Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu305 310 315 320Asp Asp21086211425212PRT213黑猩猩腺病毒-CV68纖維40086Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr1 5 10 15Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro20 25 30Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser35 40 45Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu50 55 60Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser65 70 75 80Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr85 90 95Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu100 105 110Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu115 120 125Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser130 135 140Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp165 170 175Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp180 185 190Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser195 200 205Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu210 215 220Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn225 230 235 240Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro245 250 255Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu260 265 270Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val275 280 285Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln290 295 300Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser305 310 315 320Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly325 330 335Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr340 345350Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val355 360 365Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu370 375 380Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr385 390 395 400Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser405 410 415Tyr Thr Phe Ser Tyr Ile Ala Gln Glu420 425
21087211954212PRT213黑猩猩腺病毒-ChAd20六鄰體40087Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn ProCys Glu Trp Asp Glu Ala Ala Thr Ala Leu Asp Ile130135 140Asp Leu Asn Ala Glu Asp Asp Glu Glu Ser Asp Glu Ala Gln Gly Glu145 150 155 160Ala Asp Gln Gln Lys Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly165 170 175Gln Asn Ile Thr Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Ala Ser180 185 190Gln Ala Gln Thr Pro Val Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro195 200 205Gln Val Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser Tyr Gly Ala
210 215 220Gly Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser225 230 235 240Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu Glu245 250 255Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe Ser Thr260 265 270Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro Lys Val Val275 280 285Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp Thr His Ile Ser290 295 300Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg Glu Leu Leu Gly Gln305 310 315 320Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe325 330 335Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala340 345 350Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn355 360 365Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr370 375 380Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp385 390 395 400Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr405 410 415Cys Phe Pro Leu Gly Gly Val Ile Asn Thr Glu Thr Phe Thr Lys Val420 425 430Lys Pro Lys Ala Ala Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe435 440445Ser Asp Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile450 455 460Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala465 470 475 480Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln Ile
485 490 495Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val Val Ala500 505 510Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu515 520 525Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly530 535 540Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe545 550 555 560His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu565 570 575Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn580 585 590Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala595 600 605Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met610 615 620Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr625 630 635 640Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr645 650 655Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg660 665 670Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys675 680 685Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser690 695 700Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe705 710 715 720Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn725 730 735Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser Val Asp740 745 750Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
755 760 765Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr770775 780Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe785 790 795 800Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr805 810 815Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly820 825 830Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe835 840 845Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys850 855 860Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn865 870 875 880Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln Asn Leu Leu Tyr885 890 895Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met900 905 910Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val915 920 925Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg930935 940Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 95021088211940212PRT213黑猩猩腺病毒-ChAd 4六鄰體40088Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
15 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Ala130 135 140Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly145 150 155 160Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys165 170 175Asp Asp Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro180 185 190Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly195 200 205Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe210 215 220Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp225 230 235 240Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro245 250 255Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met260 265 270Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile
275 280 285Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys Val Asn Leu Cys290 295 300Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn305 310 315 320Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu325 330 335Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg340 345 350Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg355 360 365Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro370 375 380Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn385 390 395 400Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly405 410 415Val Lys Pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser420 425 430Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met435 440 445Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn450 455 460Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile465 470 475 480Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val485 490 495Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp500 505 510Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn515 520 525Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val530 535 540Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu
545 550 555 560Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp565 570 575Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp580 585 590Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe595 600 605Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn610 615 620Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met625 630 635 640Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro645 650 655Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys660 665 670Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val675680 685Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His690 695 700Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro705 710 715 720Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr725 730 735Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp740 745 750Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly755 760 765Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg770 775 780Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys785 790 795 800Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe805 810 815Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala
820 825 830Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr835 840 845Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser850 855 860Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met865 870 875 880Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp885 890 895Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp900 905 910Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr915 920 925Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935 94021089211940212PRT213黑猩猩腺病毒-ChAd 5六鄰體40089Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asr Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Ala130 135 140Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly145 150 155 160Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys165 170 175Asp Asp Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro180 185 190Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly195 200 205Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe210 215 220Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp225 230 235 240Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro245 250 255Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met260 265 270Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile275 280 285Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys Val Asn Leu Cys290 295 300Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn305 310 315 320Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu325 330 335Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg340 345 350Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg
355 360 365Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro370 375 380Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn385 390 395 400Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly405 410 415Val Lys Pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser420 425 430Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met435 440 445Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn450 455 460Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile465 470 475 480Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val485 490 495Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp500 505 510Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn515 520 525Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val530 535 540Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu545 550 555 560Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp565 570 575Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp580 585 590Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe595 600 605Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn610 615 620Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
625 630 635 640Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn VaL Pro Ile Ser Ile Pro645 650 655Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys660 665 670Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val675 680 685Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His690 695 700Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro705 710 715 720Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr725 730 735Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp740 745 750Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly755 760 765Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg770 775 780Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys785 790 795 800Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe805 810 815Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala820 825 830Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val Thr835 840 845Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser850 855 860Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met865 870 875 880Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp885 890 895Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp
900 905 910Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr915 920 925Leu Arg Thr Pro Phe Ser Ala Gly Lys Ala Thr Thr930 935 94021090211940212PRT213黑猩猩腺病毒-ChAd 7六鄰體40090Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Lys Asn Ala130 135 140Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly145 150 155 160Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys
165 170 175Asp Gly Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro180 185 190Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly195 200 205Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe210 215 220Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp225 230 235240Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro245 250 255Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met260 265 270Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile275280 285Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Glu Val Asn Leu Cys290 295 300Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn305 310 315 320Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu325 330 335Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg340 345 350Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg355 360 365Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro370 375 380Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn385 390 395400Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly405 410 415Val Lys pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser420 425 430Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met
435 440 445Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn450 455 460Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile465 470 475 480Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val485 490 495Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp500 505 510Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn515 520 525Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val530 535 540Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu545 550 555 560Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp565 570 575Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp580 585 590Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe595 600 605Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn610 615 620Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met625 630 635640Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro645 650 655Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys660 665 670Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val675 680 685Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His690 695 700Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro
705 710 715 720Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr725 730 735Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp740 745 750Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly755 760 765Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg770 775 780Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys785 790 795 800Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe805 810 815Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala820 825 830Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr835 840 845Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser850 855 860Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met865 870 875 880Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp885 890 895Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp900 905 910Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr915 920 925Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935 94021091211930212PRT
213黑猩猩腺病毒-ChAd 9六鄰體40091Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala15 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Thr Tyr Thr Asp Asn Gln Thr Glu Lys130 135 140Thr Ala Thr Tyr Gly Asn Ala Pro Val Glu Gly Ile Asn Ile Thr Lys145 150 155 160Asp Gly Ile Gln Leu Gly Thr Asp Ser Asp Gly Gln Ala Ile Tyr Ala165 170 175Asp Glu Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Pro Glu Trp His180 185 190Asp Thr Thr Gly Thr Glu Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro195 200 205Ala Thr Asp Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn210 215 220Val Lys Gly Gly Gln Ala Lys Ser Arg Thr Lys Thr Asp Gly Thr Thr225 230 235 240
Glu Pro Asp Ile Asp Met Ala Phe Phe Asp Gly Arg Asn Ala Thr Thr245 250 255Ala Gly Leu Thr Pro Glu Ile Val Leu Tyr Thr Glu Asn Val Asp Leu260 265 270Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp Asp Ser275 280 285Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn290 295 300Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser305 310 315 320Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala325 330 335Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu340 345 350Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln355 360 365Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly370 375 380Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Ala Val Gly385 390 395 400Arg Thr Asn Ser Tyr Gln Gly Ile Lys Pro Asn Gly Gly Asp Pro Ala405 410 415Thr Trp Ala Lys Asp Glu Ser Val Asn Asp Ser Asn Glu Leu Gly Lys420 425 430Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg435 440 445Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys450 455 460Tyr Thr Pro Ala Asn Ile Thr Leu Pro Ala Asn Thr Asn Thr Tyr Asp465 470 475 480Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile485 490 495Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro500505 510
Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu515 520 525Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe530 535 540Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu545 550 555560Trp Asr Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly565 570 575Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn580 585 590Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu595 600 605Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr610 615 620Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn625 630 635 640Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp645 650 655Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly660 665 670Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly675 680 685Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp690 695 700Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu705 710 715 720Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln725 730 735Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr740 745 750Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg755 760 765Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val770775 780
Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln785 790 795 800His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln805 810 815Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser820 825 830Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met835 840 845Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr850 855 860Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp865 870 875 880Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val885 890 895Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly900 905 910Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala915 920 925Thr Thr93021092211930212PRT213黑猩猩腺病毒-ChAd 10六鄰體40092Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Thr Tyr Thr Asp Asn Gln Thr Glu Lys130 135 140Thr Ala Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser Ile Thr Lys145 150 155 160Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro Ile Tyr Ala165 170 175Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala Glu Trp His180 185 190Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro195 200 205Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn210 215 220Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly Gly Thr Lys225 230 235 240Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser Ala Ala Ala245 250 255Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn Val Asp Leu260 265 270Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp Asp Ser275 280 285Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn290 295 300Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser305 310 315 320
Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala325 330 335Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu340 345 350Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln355 360 365Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly370 375 380Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Ala Val Gly385 390 395 400Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Ala Asp Gln Thr405 410 415Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu Leu Gly Lys420 425 430Gly Asr Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg435 440 445Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys450 455 460Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp465 470 475 480Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile485 490 495Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro500 505 510Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu515 520 525Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe530 535 540Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu545 550 555 560Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly565 570 575Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn580 585 590
Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu595 600 605Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr610 615 620Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn625 630 635 640Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp645 650 655Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly660 665670Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly675 680 685Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp690 695 700Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu705 710 715 720Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln725 730 735Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr740 745 750Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg755 760 765Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val770 775 780Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln785 790 795 800His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln805 810 815Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser820 825 830Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met835 840 845Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr850 855 860
Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp865 870 875 880Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val885 890 895Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly900 905 910Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala915 920 925Thr Thr93021093211960212PRT213黑猩猩腺病毒-ChAd 11六鄰體40093Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135140Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu145 150 155 160Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu165 170 175Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala180 185 190Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro195 200 205Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val210 215 220Ala Gly Gly Arg Val Leu Lys Lys Thr Thr Pro Met Lys Pro Cys Tyr225 230 235 240Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu245 250 255Ala Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe260 265 270Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Ala Asn Asn Ile Gln Pro275 280 285Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr290 295 300His Leu Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Val Met305 310 315 320Leu Gly Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg325 330 335Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly340 345 350Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Va1 Val Asp Leu Gln355 360 365Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly370 375 380Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr385 390 395 400Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr420 425 430Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp435 440 445Thr Lys Asp Glu Thr Phe Ala Glu Arg Asn Glu Ile Gly Val Gly Asn450 455 460Asn Phe Ala Met Glu Ile Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe465 470 475 480Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn485 490 495Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met500 505 510Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu515 520 525Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn530 535 540His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn545 550 555 560Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala565 570 575Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn580 585 590Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp595 600 605Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr610 615 620Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala625 630 635 640Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser645 650 655Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro660 665 670Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp690 695 700Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe705 710 715 720Tyr Leu Asn His Thr Phe Lys Lys Val Ser Va1 Thr Phe Asp Ser Ser725 730 735Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu740 745 750Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn755 760 765Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile770 775 780Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr785 790 795 800Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln805 810 815Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn820 825 830Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln835 840 845Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val850 855 860Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg865 870 875 880Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu885 890 895Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr900 905 910Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe915 920 925Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile930 935 940Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 955 960
21094211944212PRT213黑猩猩腺病毒-ChAd 16六鄰體40094Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Thr Glu Asn Gly Gly Gly Gln130 135 140Ala Thr Thr Lys Thr His Thr Tyr Gly Val Ala Pro Met Gly Gly Thr145 150 155 160Asn Ile Thr Val Asp Gly Leu Gln Ile Gly Thr Asp Ala Thr Ala Asp165 170 175Thr Glu Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln180 185 190Ile Gly Glu Glu Asn Trp Gln Glu Thr Glu Ser Phe Tyr Gly Gly Arg195 200 205
Ala Leu Lya Lys Asp Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala210 215 220Arg Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Leu Lys Val Gly Ala225 230 235 240Asp Gly Leu Pro Thr Lys Glu Phe Asp Ile Asp Leu Ala Phe Phe Asp245 250 255Thr Pro Gly Gly Thr Val Thr Gly Gly Thr Glu Glu Tyr Lys Ala Asp260 265 270Ile Val Met Tyr Thr Glu Asn Thr Tyr Leu Glu Thr Pro Asp Thr His275 280 285Val Val Tyr Lys Pro Gly Lys Asp Asn Thr Ser Ser Lys Ile Asn Leu290 295 300Val Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp305 310 315 320Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val325 330 335Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp340 345 350Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp355 360 365Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp370 375 380Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro385 390 395 400Asn Tyr Cys Phe Pro Leu Asp Gly Ser Gly Thr Asn Ala Ala Tyr Gln405 410 415Gly Val Lys Val Lys Asn Gly Gln Asp Gly Asp Val Glu Ser Glu Trp420 425 430Glu Lys Asp Asp Thr Val Ala Ala Arg Asn Gln Leu Cys Lys Gly Asn435 440 445Ile Phe Ala Met Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe450 455 460Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr465 470 475 480
Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met485 490 495Asn Gly Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile500 505 510Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn515 520 525His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn530 535 540Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala545 550 555 560Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn565 570 575Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp580 585 590Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr595 600 605Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala610 615 620Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser625 630 635 640Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro645 650 655Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe660 665 670Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp675 680 685Pro Tyr Phe VaI Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe690 695 700Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser705 710 715 720Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu725 730 735Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn740 745 750
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile755 760 765Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr770 775 780Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu785 790 795 800Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn805 810 815Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln820 825 830ProTyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val835840 845Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg850 855 860Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu865 870 875 880Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn885 890 895Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe900 905 910Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile915 920 925Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935 94021095211960212PRT213黑猩猩腺病毒-ChAd 17六鄰體40095Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Lau Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu130 135 140Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu145 150 155 160Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu165 170 175Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala180 185 190Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro195 200 205Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val210 215 220Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr225 230 235 240Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu245250 255Thr Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe260 265 270Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Thr Asn Asn Ile Gln Pro275 280 285
Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr290 295 300His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile Met305 310 315 320Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg325 330 335Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly340 345 350Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln355 360 365Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly370 375 380Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr385 390 395 400Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu405 410 415Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr420 425 430Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp435 440 445Thr Lys Asp Glu Thr Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn450 455 460Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe465 470 475 480Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn485 490 495Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met500 505 510Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu515 520 525Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn530 535 540His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn545 550 555 560
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala565 570 575Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn580 585 590Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp595 600 605Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr610 615 620Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala625 630 635 640Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser645 650 655Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro660 665 670Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe675 680 685Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp690 695 700Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe705 710 715 720Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser725 730 735Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu740 745 750Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn755 760 765Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile770 775 780Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr785 790 795 800Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln805 810 815Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn820 825 830
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln835 840 845Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val850 855 860Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg865 870 875 880Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu885 890 895Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr900 905 910Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe915 920 925Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile930 935 940Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 955 96021096211958212PRT213黑猩猩腺病毒-ChAd 19六鄰體40096Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala130 135 140Leu Glu Asp Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu145 150 155 160Ala Pro Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly165 170 175Glu Glu Ile Thr Lys Asp Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu180 185 190Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro195 200 205Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly210 215 220Gly Arg Val Leu Lys Lys Thr Thr Pro Met Lys Pro Cys Tyr Gly Ser225 230 235 240Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu Val Ala245 250 255Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu Leu Gln Phe Phe Ser260 265 270Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly Asn Asp Thr Lys Pro Lys275 280 285Val Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr His290 295 300Ile Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Val Met Leu305 310 315 320Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp325 330 335Asn Phe Ile Gly Leu Met Tyr Tyr Asr Ser Thr Gly Asn Met Gly Val340 345 350
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp355 360 365Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp370 375 380Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp385 390 395 400Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro405 410 415Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln420 425 430Val Ile Lys Thr Asn Gly Asn Gly Gln Ala Asp Pro Thr Trp Glu Lys435 440 445Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe450 455 460Ala Met Glu Ile Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr465 470 475 480Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser485 490 495Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys500 505 510Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala515 520 525Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His530 535 540Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg545 550 555 560Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys565 570 575Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg580 585 590Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg595 600 605Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr610 615 620
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu625 630 635 640Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala645 650 655Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser660 665 670Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg675 680 685Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr690 695 700Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu705 710 715 720Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser725 730 735Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys740 745 750Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr755 760 765Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr770 775 780Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe785 790 795 800Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys805 810 815Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser820 825 830Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr835 840 845Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser850 855 860Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro865 870 875 880Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln885 890 895
Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu900 905 910Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val915 920 925Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr930 935 940Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 955210972112865212DNA213黑猩猩腺病毒-ChAd 8六鄰體40097atggccaccc catcgatgtt gccccagtgg gcatacatgc acatcgccgg acaggatgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120ctggggaaca agtttaggaa ccccaccgtg gcccccaccc acgatgtgac caccgaccga 180agccagcggc tgatgctgcg ctttgtgccc gttgatcggg aggacaatac ctactcatac 240aaagttcgct acacactggc tgtgggcgac aacagagtgc tggatatggc cagcaccttc 300tttgacatcc ggggggtgct tgacagaggt cccagtttca agccatactc tggcacggct 360tacaactcct tggctcctaa gggtgccccc aatacatgcc agtggatagc taaagggtcg 420cccgttcaag atgatgctga acaagctcag gaacaaaaag atgttaccta tacttttggc 480aatgcgccag taaaagcaga agatgacatt acaaaagacg gattagaagt aggcatacaa 540attattggtg atgaggagaa tcccatttat gcagataaaa catatcaacc agagccacag 600gttggtgacg agcaatggca tgacacaact ggaaccactg agcagtatgg aggcagagct 660cttaagccag ctacaaacat gaggccatgc tatggctctt ttgccagacc tacaaacaaa 720aaaggagggc aagctaaaac cagaaaagta gaaaaaactg aaggtgacaa aaagactgaa 780gttgaagaac ttgacattga tatggatttt tatgatgcaa gatctaaaaa acaaggctat 840gatcctcaaa tagtgctata ttcagaaaat gtaaatctgg aaacgcccga cactcatatt 900gtgtacaaac cgggaactga tgaaaccagt tcctccacta atttgggcca gcaagctatg 960cccaacagac ccaattacat tggtttcagg gacaacttca ttggacttat gtattataac 1020agtactggta acatgggagt gctggccggt caagcttctc agttgaatgc tgtggtcgac 1080ttgcaggaca ggaacacaga actgtcctac cagctgctgc ttgactctct gggtgacaga 1140
accagatact ttagcatgtg gaatcaggcc gtggatagct atgacccaga tgtgcgcatt 1200attgaaaatc atggtgtgga agatgaactt cccaattatt gtttcccatt ggatggtgtt 1260ggtccaatta cagaaaccta tcaaggtatc aagccaaaaa cagcagacaa tgcaaatgac 1320caatgggaaa aaaataccga agtaaatgga gctaatgaaa taggaaaggg aaacaattat 1380gcaatggaaa ttaatctaca agctaacctc tggagaagtt ttctttactc caacgtggct 1440ctgtatcttc cagacggtta caaatatacc ccagccaatg ttacgctgcc agacaacaaa 1500aatacctatg ggtacataaa cggacgagta gtgtctccat ctttggtgga ttcatacatc 1560aacattggag ccagatggtc tttggatctt atggacaatg tcaacccatt taatcaccac 1620cgcaatgctg ggctgcgcta ccgttccatg cttcttggca atggacgcta tgtgcccttc 1680cacatccaag tgccgcagaa attctttgct atcaagaact tgctgcttct gccaggctcc 1740tacacctatg agtggaactt cagaaaggat gtgaacatgg tcctacaaag ttcccttggt 1800aatgatctca gaactgatgg agccagcatc agttttacca gcatcaacct ctatgccacc 1860tttttcccaa tggctcacaa cactgcttcc acccctgaag ccatgctgcg caatgacacc 1920aatgaccagt cattcaacga ctacctctct gcagccaaca tgctctaccc catccctgcc 1980aatgccacta acattcccat ctccattccc tctcgcaact gggctgcctt caggggctgg 2040tccttcacca gactcaaaac caaggagact ccctctttgg gatcagggtt cgatccctac 2100tttgtctatt caggctccat tccctacctg gatggtacct tctacctcaa ccacactttc 2160aagaaggtct ccatcatgtt tgactcctca gtcagctggc cgggcaatga cagactgttg 2220tgtcccaatg agtttgaaat caagcgcact gtggatgggg aagggtacaa cgtggctcaa 2280tgcaacatga ccaaggattg gttcttggtc cagatgcttg ccaactacaa cattggctac 2340cagggcttct acatcccaga ggggtacaag gatcgcatgt actccttctt cagaaacttc 2400cagcccatga gcagacaggt agttgatgaa gtcaattaca aggagtacca agctgtcaca 2460cttgcttacc agcacaacaa ctctggtttt gtgggttacc atgcacccac tcttcgtcag 2520ggccaaccat acccagctaa ctacccctac ccgctcattg gaaccactgc tgtcaccagc 2580gtcacccaga aaaagttctt gtgcgacagg accatgtggc gcatcccatt ctccagcaac 2640ttcatgtcca tgggtgccct taccgacctg gggcagaaca tgctttatgc caactcagcc 2700catgcgctgg acatgacttt tgaggtggat cccatggatg agcccacact gctttatctt 2760ctttttgaag tcttcgacgt ggtcagagtg caccagccac accgcggcgt catcgaggct 2820gtctacctgc gtaccccatt ctcagctggt aacgccacca cataa 286521098211954212PRT213黑猩猩腺病毒ChAd 8
40098Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Ile Ala Lys Gly Ser Pro Val Gln Asp130 135 140Asp Ala Glu Gln Ala Gln Glu Gln Lys Asp Val Thr Tyr Thr Phe Gly145 150 155 160Asn Ala Pro Val Lys Ala Glu Asp Asp Ile Thr Lys Asp Gly Leu Glu165 170 175Val Gly Ile Gln Ile Ile Gly Asp Glu Glu Asn Pro Ile Tyr Ala Asp180 185 190Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Glu Gln Trp His Asp195 200 205Thr Thr Gly Thr Thr Glu Gln Tyr Gly Gly Arg Ala Leu Lys Pro Ala210 215 220Thr Asn Met Arg Pro Cys Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys225 230 235 240Lys Gly Gly Gln Ala Lys Thr Arg Lys Val Glu Lys Thr Glu Gly Asp245 250 255Lys Lys Thr Glu Val Glu Glu Leu Asp Ile Asp Met Asp Phe Tyr Asp260 265 270
Ala Arg Ser Lys Lys Gln Gly Tyr Asp Pro Gln Ile Val Leu Tyr Ser275 280 285Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Pro290 295 300Gly Thr Asp Glu Thr Ser Ser Ser Thr Asn Leu Gly Gln Gln Ala Met305 310 315 320Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu325 330 335Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala340 345 350Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu355 360 365Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe370 375 380Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile385 390 395 400Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro405 410 415Leu Asp Gly Val Gly Pro Ile Thr Glu Thr Tyr Gln Gly Ile Lys Pro420 425 430Lys Thr Ala Asp Asn Ala Asn Asp Gln Trp Glu Lys Asn Thr Glu Val435 440 445Asn Gly Ala Asn Glu Ile Gly Lys Gly Asn Asn Tyr Ala Met Glu Ile450 455 460Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala465 470 475 480Leu Tyr Leu Pro Asp Gly Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu485 490 495Pro Asp Asn Lys Asn Thr Tyr Gly Tyr Ile Asn Gly Arg Val Val Ser500 505 510Pro Ser Leu Val Asp Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu515 520 525Asp Leu Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly530 535 540
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe545 550 555 560His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu565 570 575Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn580 585 590Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala595 600 605Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met610 615 620Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr625 630 635 640Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr645 650 655Pro Ile Pro Ala Asn Ala Thr Asn Ile Pro Ile Ser Ile Pro Ser Arg660 665 670Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys675 680 685Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser690 695 700Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe705 710 715 720Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro Gly Asn725 730 735Asp Arg Leu Leu Cys Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp740 745 750Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe755 760 765Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr770 775 780Ile Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe785 790 795 800Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Glu Tyr805 810 815
Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly820 825 830Tyr His Ala Pro Thr Leu Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr835 840 845Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr Gln Lys850 855 860Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser Ser Asn865 870 875 880Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr885 890 895Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met900 905 910Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp Val Val915 920 925Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg930 935 940Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950210992112871212DNA213黑猩猩腺病毒-ChAd 22六鄰體40099atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcaat 120ctggggaaca agtttaggaa ccctaccgtg gcgcccaccc atgatgtgac caccgaccgc 180agtcaacggc tgatgctccg ctttgtgccc gttgaccggg aggacaatac ctactcatac 240aaagttcgat acaccttggc tgtgggcgac aacagagtgc tggatatggc cagtactttc 300tttgacattc ggggtgtgtt ggatagaggc cctagcttca agccatattc tggcactgct 360tacaactcat tggcccctaa gggcgctccc aatacatctc agtggattgc tgaaggcgta 420aaaaaagaaa atggggaagc tgacaatgaa gcagctgtcg aagaggaaga ggaagagaaa 480
aatcttacca cttacacttt tggaaatgcc ccagtgaaag cagaaggtgg tgatatcact 540aaagacaaag gtcttccaat tggttcagaa attacagacg gcgaagccaa accaatttat 600gcagataaac tataccaacc agaacctcag gtgggagagg aaacttggac tgacacagat 660ggaacaactg agaagtatgg tggtagagct ctaaagccag aaactaaaat gaaaccctgc 720tatgggtctt ttgctaaacc cactaacgtc aaaggcggac aggcaaaaca aaaaactact 780gaacaactgc aaaaccagca ggttgaatat gatattgaca tgaacttttt tgatcaagcg 840tcacagaaag caaacttcag tccaaaaatt gtgatgtatg cagaaaatgt agacttggaa 900accccagaca ctcacgtggt gtacaaacct ggtacttcag aagaaagttc tcatgctaat 960ctcggtcaac aatctatgcc caacagaccc aactacattg gctttagaga taactttatt 1020ggacttatgt actacaacag tactggcaac atgggagtgc tggcaggtca agcatcccaa 1080ttgaatgcgg tggttgactt gcaggacaga aacacagaac tatcatatca actactgctt 1140gattctctgg gtgacagaac cagatacttc agcatgtgga atcaagcagt cgatagctat 1200gatcctgatg tgcgcattat tgaaaatcat ggggtggaag atgagcttcc caactactgc 1260tttccattgg atggagtagg ggtaccaaca actagttaca aaataattga accaaatgga 1320gagggtgcag attggaaaga gcctgacata aatggaacaa gtgaaattgg acaaggaaat 1380ctctttgcca tggaaattaa cctccaagct aatctctgga gaagttttct ttattccaat 1440gtggctctgt atctcccaga ctcctacaaa tacaccccag ccaatgtcac tcttccaact 1500aacaccaaca cttatgacta catgaatggg cgggtggttc ccccatccct agtggatacc 1560tacgtaaaca ttggcgccag atggtctttg gatgccatgg acaatgtcaa cccctttaac 1620catcaccgca acgctggcct gcgataccgg tccatgcttttgggcaatgg tcgctacgtg 1680cctttccaca ttcaagtgcc tcagaaattc tttgctgtga agaacctgct gcttctaccc 1740ggttcttaca cctacgagtg gaacttcaga aaggatgtga acatggtcct gcagagttcc 1800cttggtaatg atctccgggt cgatggtgcc agcatcagtt ttaccagcat caatctctat 1860gccaccttct tccccatggc ccacaacact gcctccaccc ttgaagccat gctgcgcaat 1920gacaccaatg atcaatcatt caatgactac ctttctgcag ccaacatgct ctaccccatc 1980ccggccaacg ctaccaacgt tcccatctcc attccctctc gtaactgggc cgccttcaga 2040ggctggtcct tcaccagact caaaaccaaa gagactccct ctttgggatc agggttcgat 2100ccctactttg tttactctgg ttctatacct tacctggatg gtaccttcta ccttaaccac 2160acttttaaga aagtctctat catgtttgac tcttcagtca gctggcctgg taatgacaga 2220ttgctaactc caaatgagtt cgaaatcaag cgcacagttg atggggaagg ctacaatgtg 2280gcccaatgta acatgaccaa agactggttc ctggtccaga tgcttgccaa ctacaacatt 2340ggataccagg gcttctacgt tcctgagggt tacaaggatc gcatgtactc cttcttcaga 2400aacttccagc ccatgagtag acaggtggtt gatgagatta actacaaaga ctataaagct 2460gtcgccgtac cctaccagca taataactct ggctttgtgg gttacatggc tcctaccatg 2520cgtcagggtc aagcgtaccc tgctaactac ccataccccc taattggaac cactgcagta 2580
accagtgtca cccagaaaaa attcctgtgc gacaggacca tgtggcgcat cccattctct 2640agcaacttca tgtccatggg tgcccttaca gacctgggac agaacttgct gtatgccaac 2700tcagcccatg cgctggacat gacttttgag gtggatccca tggatgagcc caccctgctt 2760tatcttcttt ttgaagtatt cgacgtggtc agagtgcacc aaccacaccg cggcgtcatc 2820gaggccgtct acctgcgcac accgttctcg gctggtaacg ccaccacata a 2871210100211956212PRT213黑猩猩腺病毒-ChAd 22六鄰體400100Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Ser Gln Trp Ile Ala Glu Gly Val Lys Lys Glu Asn130 135 140Gly Glu Ala Asp Asn Glu Ala Ala Val Glu Glu Glu Glu Glu Glu Lys145 150 155 160Asn Leu Thr Thr Tyr Thr Phe Gly Asn Ala Pro Val Lys Ala Glu Gly165 170 175
Gly Asp Ile Thr Lys Asp Lys Gly Leu Pro Ile Gly Ser Glu Ile Thr180 185 190Asp Gly Glu Ala Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln Pro Glu195 200 205Pro Gln Val Gly Glu Glu Thr Trp Thr Asp Thr Asp Gly Thr Thr Glu210 215 220Lys Tyr Gly Gly Arg Ala Leu Lys Pro Glu Thr Lys Met Lys Pro Cys225 230 235 240Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val Lys Gly Gly Gln Ala Lys245 250 255Gln Lys Thr Thr Glu Gln Leu Gln Asn Gln Gln Val Glu Tyr Asp Ile260265 270Asp Met Asn Phe Phe Asp Gln Ala Ser Gln Lys Ala Asn Phe Ser Pro275 280 285Lys Ile Val Met Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr290 295 300His Val Val Tyr Lys Pro Gly Thr Ser Glu Glu Ser Ser His Ala Asn305 310 315 320Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg325 330 335Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly340 345 350Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln355 360 365Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly370 375 380Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr385 390 395 400Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu405 410415Pro Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Val Pro Thr Thr Ser420 425 430Tyr Lys Ile Ile Glu Pro Asn Gly Glu Gly Ala Asp Trp Lys Glu Pro435 440 445
Asp Ile Asn Gly Thr Ser Glu Ile Gly Gln Gly Asn Leu Phe Ala Met450 455 460Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn465 470 475 480Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Val485 490 495Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val500 505 510Val Pro Pro Ser Leu Val Asp Thr Tyr Val Asn Ile Gly Ala Arg Trp515 520 525Ser Leu Asp Ala Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn530 535 540Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val545 550 555 560Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Val Lys Asn Leu565 570 575Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp580 585 590Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp595 600 605Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe610 615 620Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn625 630 635 640Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met645 650 655Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro660 665 670Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys675 680 685Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val690 695 700Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His705 710 715 720
Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro725 730 735Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr740 745 750Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp755 760 765Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly770 775 780Phe Tyr Val pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg785 790 795 800Asn Phe Gln pro Met Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys805 810 815Asp Tyr Lys Ala Val Ala Val Pro Tyr Gln His Asn Asn Ser Gly Phe820 825 830Val Gly Tyr Met Ala Pro Thr Met Arg Gln Gly Gln Ala Tyr Pro Ala835 840 845Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr850 855 860Gln Lys Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser865 870 875 880Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu885 890 895Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp900 905 910Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp915 920 925Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr930 935 940Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 9552101012112865
212DNA213黑猩猩腺病毒-ChAd 24六鄰體400101atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcc 360tacaactccc tggcccccaa gggcgcgccc aacccatgcg agtgggatga ggctgctact 420gcccttgaca ttgatttgaa cgcagaagaa gatgaagaag gcgatgaagc ccaaggggaa 480gcagatcagc agaaaactca tgtatttggc caggcgccat actccggaca gaacattaca 540aaagaaggca tacagatagg cattgatgct accagtcaag cccaaacacc tctatatgcc 600gacaaaacat tccaacccga acctcaggtt ggagaatcac aatggaatga gacagagatt 660agccatggag cgggacgggt gctaaaaaag accactctca tgaaaccttg ctatgggtca 720tatgcaaggc ctactaatga gaacggaggt cagggcatcc tcctggaaca agatggaaag 780aaagaaagtc aagtggaaat gcaatttttc tccactactc aggcagctgc gggtaattca 840gataatccta ctccaaagct tgttttgtac agcgaggatg ttaacctgga aacaccagat 900acacacattt catacatgcc cactaacaac gaaaccaatt caagagaact gttgggacaa 960caggccatgc ccaacaggcc taattacatc ggcttcagag acaactttat cggtctcatg 1020tactacaaca gcactggcaa catgggagtg cttgcaggtc aggcctctca gttgaatgca 1080gtggtggact tgcaagacag aaacacagaa ctgtcctacc agctcttgct tgattccatg 1140ggtgacagaa ccagatattt ctccatgtgg aatcaggcag tggacagtta tgacccagat 1200gtcagaatta ttgaaaatca tggaaccgaa gacgagctcc ccaactactg ttttcctctg 1260ggtggcataa tcaatacgga aacttttaca aaagtcaagc ctaaagctgg acaggacgct 1320cagtgggaaa aagattcaga attttcagat aaaaatgaaa taagagtggg aaacaacttc 1380gctatggaaa tcaacatcaa tgccaacctg tggaggaact tcctgtactc caacgtggcc 1440ctgtacctgc cagacaagct taagtatact ccatccaatg tgcaaatttc caacaacccc 1500aactcctacg attacatgaa caagcgagtg gtggccccgg ggctggtgga ctgctacatc 1560aacctgggcg cgcggtggtc gctggactac atggacaacg tcaacccctt caaccaccac 1620cgcaacgcgg gcctgcgcta ccgctccatg ctcctgggca acgggcgcta cgtgcccttc 1680cacatccagg tgccccagaa gttctttgcc atcaagaacc tcctcctcct gccgggctcc 1740tacacctacg agtggaactt caggaaggat gtcaacatgg tcctccagag ctctctgggc 1800aacgatctca gggtggacgg ggccagcatc aagttcgaga gcatctgcct ctacgccacc 1860
ttcttcccca tggcccacaa cacggcctcc acgctcgagg ccatgctcag gaacgacacc 1920aacgaccagt ccttcaatga ctacctctcc gccgccaaca tgctctaccc catccccgcc 1980aacgccacca acgtccccat ctccatcccc tcgcgcaact gggcggcctt ccgcggctgg 2040gccttcaccc gcctcaagac caaggagacc ccctccctgg gctcgggatt cgacccctac 2100tacacctact cgggatccat tccctacctg gacggcacct tctacctcaa ccacactttc 2160aagaaggtct cggtcacctt cgactcctcg gtcagctggc cgggcaacga ccgcctgctc 2220acccccaacg agttcgagat caagcgctcg gtcgacgggg agggctacaa cgtggcccag 2280tgcaacatga ccaaggactg gttcctggtc cagatgctgg ccaactacaa catcggctac 2340cagggcttct acatcccaga gagctacaag gacaggatgt actccttctt caggaacttc 2400cagcccatga gccggcaggt ggtggaccag accaagtaca aggactacca ggaggtgggc 2460atcatccacc agcacaacaa ctcgggcttc gtgggctacc tcgcccccac catgcgcgag 2520ggacaggcct accccgccaa cttcccctac ccgctcatag gcaagaccgc ggtcgacagc 2580atcacccaga aaaagttcct ctgcgaccgc accctctggc gcatcccctt ctccagcaac 2640ttcatgtcca tgggtgcgct cacggacctg ggccagaacc tgctctatgc caactccgcc 2700cacgcgctcg acatgacctt cgaggtcgac cccatggacg agcccaccct tctctatgtt 2760ctgttcgaag tctttgacgt ggtccgggtc caccagccgc accgcggcgt catcgagacc 2820gtgtacctgc gcacgccctt ctcggccggc aacgccacca cctaa 2865210102211954212PRT213黑猩猩腺病毒-ChAd 24六鄰體400102Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Pro Cys Glu Trp Asp Glu Ala Ala Thr Ala Leu Asp Ile130 135 140Asp Leu Asn Ala Glu Glu Asp Glu Glu Gly Asp Glu Ala Gln Gly Glu145 150 155 160Ala Asp Gln Gln Lys Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly165 170 175Gln Asn Ile Thr Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Thr Ser180 185 190Gln Ala Gln Thr Pro Leu Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro195 200 205Gln Val Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser His Gly Ala210 215 220Gly Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser225 230 235 240Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu Glu245 250 255Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe Ser Thr260 265 270Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro Lys Leu Val275 280 285Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp Thr His Ile Ser290 295 300Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg Glu Leu Leu Gly Gln305 310 315 320Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe325 330 335Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala340 345 350Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn355 360 365
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr370375 380Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp385 390 395 400Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr405 410 415Cys Phe Pro Leu Gly Gly Ile Ile Asn Thr Glu Thr Phe Thr Lys Val420 425 430Lys Pro Lys Ala Gly Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe435 440 445Ser Asp Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile450 455 460Asn Ile Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala465 470 475 480Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln Ile485 490 495Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val Val Ala500 505 510Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu515 520 525Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly530 535 540Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe545 550 555 560His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu565 570 575Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn580 585 590Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala595 600 605Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met610 615 620Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr625 630 635 640
Asn Asp Gln Ser phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr645 650 655Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg660 665 670Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys675 680 685Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser690 695 700Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe705 710 715 720Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn725 730 735Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser Val Asp740 745 750Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe755 760 765Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr770775 780Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe785 790 795 800Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr805 810 815Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly820 825 830Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe835 840 845Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys850 855 860Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn865 870 875 880Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu Leu Tyr885 890 895Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met900 905 910
Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val915 920 925Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg930 935 940Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 9502101032112841212DNA213黑猩猩腺病毒-ChAd 26六鄰體400103atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggctcccaa gggagcaccc aattccagcc agtgggagca aaaaaagaca 420ggcaataaca atggaaatgg cggcactgaa tctgttacct ttggtgtagc cgccatgggc 480ggagagaata ttacaaaaga gggtcttcaa attggaagtg atgaaactaa aaccgataac 540aaagaaattt atgcagacaa gacctaccaa cctgagcctc aaataggaga ggagaactgg 600caagaaacat tctcttttta tggtggtaga gctcttaaaa aagatactaa gatgaaacca 660tgctatggct cctttgctag gcccacaaat gaaaagggag gtcaggccaa atttaaagtt 720caagacggtg tgcagactac agaatatgac atcgacctgg ctttctttga tattccaagc 780accggcacag ggggcaatgg tacaaatgta aatgataagc cagacatggt catgtacact 840gaaaatgtga atttggagac gccagatact catattgtgt acaaacctgg aacttcagat 900gacagctcta aagccaactt gtgccagcag gccatgccaa acagacccaa ctacattggt 960ttcagagaca actttattgg gctcatgtat tacaacagta ctggcaatat gggggtgctg 1020gctggtcagg cctctcagct gaatgctgtg gtcgacttgc aagacagaaa caccgaactg 1080tcttaccagc tcttgctcga ctctctgggt gacagaacca ggtatttcag tatgtggaac 1140caggcggtgg acagttatga ccctgatgtg cgcattattg aaaaccatgg tgtggaggat 1200gaattgccaa actattgctt ccccttggat ggagctggca ctaatgctgt ataccagggt 1260
gttaaagcaa aagataacgg aaacgcagcc aatggaaact gggaacaaga cacaggcgtt 1320tcaagtatta accagatatg caaggggaac atctatgcca tggaaatcaa cattcaagcc 1380aacctgtgga gaagtttcct ttactcgaac gtggccctgt acctgcccga ctcttacaag 1440tacacgccgg ccaacatcac cctgcccacc aacaccaaca cctacgatta catgaacggt 1500cgggtggtgc ctccctcgct ggtggacgcc tacatcaaca tcggggcgcg ctggtcgctg 1560gaccccatgg acaacgtcaa tcccttcaac caccaccgca acgcgggcct gcgctaccgc 1620tccatgctcc tgggcaacgg gcgctacgtg cccttccaca tccaggtgcc ccagaaattt 1680ttcgccatca agagcctcct gctcctgccc gggtcctaca cctacgagtg gaacttccgc 1740aaggacgtca acatgatcct gcagagctcc ctcggcaacg acctgcgcac ggacggggcc 1800tccatctcct tcaccagcat caacctctac gccaccttct tccccatggc gcacaacacg 1860gcttccacgc tcgaggccat gctgcgcaac gacaccaacg accagtcctt caacgactac 1920ctctcggcgg ccaacatgct ctaccccatc ccggccaacg ccaccaacgt gcccatctcc 1980atcccctcgc gcaactgggc cgccttccgc ggctggtcct tcacgcgtct caagaccaag 2040gaaacgccct cgctgggctc cgggttcgac ccctacttcg tctactcggg ctccatcccc 2100tacctcgacg gcaccttcta cctcaaccac accttcaaga aggtctccat caccttcgac 2160tcctccgtca gctggcccgg caacgaccgg ctcctgacgc ccaacgagtt cgaaatcaag 2220cgcaccgtcg acggcgaggg ctacaacgtg gcccagtgca acatgaccaa ggactggttc 2280ctggtccaga tgctggccca ctacaacatc ggctaccagg gcttctacgt gcccgagggc 2340tacaaggacc gcatgtactc cttcttccgc aacttccagc ccatgagccg ccaggtggtg 2400gacgaggtca actacaagga ctaccaggcc gtcaccctgg cctaccagca caacaactcg 2460ggcttcgtcg gctacctcgc gcccaccatg cgccagggcc agccctaccc cgccaactac 2520ccctacccgc tcatcggcaa gagcgccgtc accagcgtca cccagaaaaa gttcctctgc 2580gacagggtca tgtggcgcat ccccttctcc agcaacttca tgtccatggg cgcgctcacc 2640gacctcggcc agaacatgct ctatgccaac tccgcccacg cgctagacat gaatttcgaa 2700gtcgacccca tggatgagtc cacccttctc tatgttgtct tcgaagtctt cgacgtcgtc 2760cgagtgcacc agccccaccg cggcgtcatc gaggccgtct acctgcgcac ccccttctcg 2820gccggcaacg ccaccaccta a2841210104211946212PRT213黑猩猩腺病毒-ChAd 26六鄰體400104Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Asn130 135 140Gly Asn Gly Gly Thr Glu Ser Val Thr Phe Gly Val Ala Ala Met Gly145 150 155 160Gly Glu Asn Ile Thr Lys Glu Gly Leu Gln Ile Gly Ser Asp Glu Thr165 170 175Lys Thr Asp Asn Lys Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu180 185 190Pro Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Phe Ser Phe Tyr Gly195 200 205Gly Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser210 215 220Phe Ala Arg Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Phe Lys Val225 230 235 240Gln Asp Gly Val Gln Thr Thr Glu Tyr Asp Ile Asp Leu Ala Phe Phe245 250 255Asp Ile Pro Ser Thr Gly Thr Gly Gly Asn Gly Thr Asn Val Asn Asp260 265 270Lys Pro Asp Met Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro275 280 285
Asp Thr His Ile Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys290 295 300Ala Asn Leu Cys Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly305 310 315 320Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn325 330 335Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp340 345 350Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser355 360 365Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp370 375 380Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp385 390 395 400Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ala405 410 415Val Tyr Gln Gly Val Lys Ala Lys Asp Asn Gly Asn Ala Ala Asn Gly420 425 430Asn Trp Glu Gln Asp Thr Gly Val Ser Ser Ile Asn Gln Ile Cys Lys435 440 445Gly Asn Ile Tyr Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg450 455 460Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys465 470 475 480Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp485 490 495Tyr Met Asn Gly Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile500 505 510Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro515 520 525Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu530 535 540Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe545 550 555 560
Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu565 570 575Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly580 585 590Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn595 600 605Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu610 615 620Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr625 630 635 640Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn645 650 655Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp660 665 670Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly675 680 685Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly690 695 700Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp705 710 715 720Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu725 730 735Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln740 745 750Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr755760 765Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg770 775 780Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val785 790 795 800Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln805 810 815His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln820 825830
Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser835 840 845Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met850 855 860Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr865 870 875 880Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp885 890 895Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val900 905910Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly915 920 925Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala930 935 940Thr Thr9452101052112838212DNA213黑猩猩腺病毒-ChAd 30六鄰體400105atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120ctggggaaca agtttaggaa ccccaccgtg gcacccaccc acgatgtgac caccgaccga 180agccagcggc tgatgctgcg ctttgtgccc gttgatcgtg aggacaatac ttactcgtac 240aaagttcgtt acacactggc tgtgggcgac aacagagtgc tagatatggc cagcaccttc 300tttgacatca gaggggtgct tgacagaggt cccagcttca agccctactc tggcacagct 360tacaactctc tggctcctaa gggagctcct aatcctagcc aatggctaga acaatcaacg 420acagagggag aagacgatcc aactaacact acacacacat ttggaatagc ttctatgaaa 480ggagaaaaca tcaccaaaga aggtttgcaa attggaaaag aagtaaccac tactggagat 540aaaccaattt atgcagataa aacctttcag ccagaacccc aagtgggaga agagacttgg 600
actgatactg acgggacaaa tgaaaagttt ggcggtagaa ctcttaaaag tgctactaat660atgaaaccat gctatgggtc ttttgctagg cccacaaaca aacaaggcgg acaagctaaa720accagaaaag tagcggcagt tgatgggggg gaggaaactg aagaaccaga catcgacatg780gtgttttatg atgatagagg tgctacagaa gccatgatgg ctcctgaagt tgtactttat840gcagaaaatg taaatctgga aacaccagac acccatgtgg tgtacaaacc aggaacctct900gatattaatt ctcatgaaaa tttgggtcag caggctatgc caaacaggcc caattacatt960ggattcagag ataactttgt tggactcatg tactacaata gtactggcaa tatgggtgtg1020ttggcagggc aggcatcaca gctaaatgca gtagttgact tgcaagacag aaacactgag1080ctatcgtacc agctcttact tgattccctg ggcgacagaa ctcgatattt cagcatgtgg1140aaccaggctg tggatagcta tgaccctgat gtgcgcatta ttgaaaatca tggtatcgaa1200gatgaactac caaattactg cttccctctt gatggaatag gaccaggtaa aacataccaa1260ggtattaaag aaaaacaagg tgatgaggcc aacaaatggg aacaagacaa aacctatgcc1320acctctaatg aaatagccat aggtaataac ctggctatgg aaattaatat ccaggctaac1380ctttggagaa gttttctgta ctccaacgtg gctctgtacc ttccagacgc ttacaagtac1440acgccggcca acattacttt acctgccaat accaacacct atgaatacat gaacgggcga1500gtggtggcac catctttggt tgattcctac atcaacattg gtgccaggtg gtctcttgac1560ccaatggaca atgtgaaccc cttcaatcac caccgcaacg ctgggctgcg ttacagatcc1620atgcttctgg gcaatggtcg ctatgtgcct ttccacatcc aagtgcctca aaaattcttt1680gctatcaaaa acctgcttct cctccccgga tcctacacct atgagtggaa cttcagaaag1740gacgtaaaca tggtcctgca gagttccctt ggtaatgatc tcagaactga tggtgctagc1800attagtttta ccagcatcaa cctctatgcc acctttttcc caatggctca caacactgct1860tccacacttg aagccatgct gcgcaatgac accaatgacc agtcattcaa tgactacctt1920tctgcagcta acatgctcta cccaattcca gcaaatgcta ccaacattcc catttccatt1980ccctctcgca actgggctgc cttcaggggc tggtcattca ccagactcaa aaccaaggag2040actccctctt tgggatcagg ctttgatccc tactttgttt actctggctc cattccctac2100ctggatggta ccttctacct caaccacact ttcaaaaagg tttccattat gtttgattcc2160tcagtcagct ggccgggcaa tgacagattg ctaactccaa atgagttcga aatcaagcgc2220actgtggatg gggaagggta caatgtagct caatgcaaca tgaccaagga ctggttcctg2280gttcagatgc ttgccaacta taacattggc taccagggct tctacatccc agaggggtac2340aaggatcgca tgtattcctt cttcagaaac ttccagccca tgagcagaca ggtggttgat2400gaagttaatt acaaggagta ccaagccgtc acacttgctt accaacacaa caactctggc2460tttgtgggtt accttgcacc cactatgagg cagggagaac cttaccccgc taactaccca2520taccccctaa tcggaaccac tgctgttaag agtgttaccc acaaaaagtt cctgtgcgac2580aggaccatgt ggcgcatccc cttctccagc aacttcatgt ccatgggtgc ccttaccgac2640ctgggacaga acatgcttta tgccaactca tcccatgcgc tggacatgac ttttgaggtg2700
gatcccatgg atgagcccac cctgctttat cttcttttcg aagttttcga cgtggtcaga 2760gcgcaccagc cacaccgcgg cgtcatcgag gctgtctacc tgcgtactcc attctcagct 2820ggtaacgcca ccacataa2838210106211945212PRT213黑猩猩腺病毒-ChAd 30六鄰體400106Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Pro Ser Gln Trp Leu Glu Gln Ser Thr Thr Glu Gly Glu130 135 140Asp Asp Pro Thr Asn Thr Thr His Thr Phe Gly Ile Ala Ser Met Lys145 150 155 160Gly Glu Asn Ile Thr Lys Glu Gly Leu Gln Ile Gly Lys Glu Val Thr165 170 175Thr Thr Gly Asp Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu180 185 190
Pro Gln Val Gly Glu Glu Thr Trp Thr Asp Thr Asp Gly Thr Asn Glu195 200 205Lys Phe Gly Gly Arg Thr Leu Lys Ser Ala Thr Asn Met Lys Pro Cys210 215 220Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys Gln Gly Gly Gln Ala Lys225 230 235 240Thr Arg Lys Val Ala Ala Val Asp Gly Gly Glu Glu Thr Glu Glu Pro245 250 255Asp Ile Asp Met Val Phe Tyr Asp Asp Arg Gly Ala Thr Glu Ala Met260 265 270Met Ala Pro Glu Val Val Leu Tyr Ala Glu Asn Val Asn Leu Glu Thr275 280 285Pro Asp Thr His Val Val Tyr Lys Pro Gly Thr Ser Asp Ile Asn Ser290 295 300His Glu Asn Leu Gly Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile305 310 315 320Gly Phe Arg Asp Asn Phe Val Gly Leu Met Tyr Tyr Asn Ser Thr Gly325 330 335Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val340 345 350Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp355 360 365Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val370 375 380Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Ile Glu385 390 395 400Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Gly Ile Gly Pro Gly405 410 415Lys Thr Tyr Gln Gly Ile Lys Glu Lys Gln Gly Asp Glu Ala Asn Lys420 425 430Trp Glu Gln Asp Lys Thr Tyr Ala Thr Ser Asn Glu Ile Ala Ile Gly435 440 445Asn Asn Leu Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser450 455 460
Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ala Tyr Lys Tyr465 470 475 480Thr Pro Ala Asn Ile Thr Leu Pro Ala Asn Thr Asn Thr Tyr Glu Tyr485 490 495Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ser Tyr Ile Asn500 505 510Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe515 520 525Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly530 535 540Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe545 550 555 560Ala Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp565 570 575Asn Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn580 585 590Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu595 600 605Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu610 615 620Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu625 630 635 640Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Ile645 650 655Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser660 665 670Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe675 680 685Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr690 695 700Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser705 710 715 720Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe725 730 735
Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asr Val Ala Gln Cys740 745 750Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn755 760 765Ile Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Gly Tyr Lys Asp Arg Met770 775 780Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp785 790 795 800Glu Val Asn Tyr Lys Glu Tyr Gln Ala Val Thr Leu Ala Tyr Gln His805 810 815Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly820 825 830Glu Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala835 840 845Val Lys Ser Val Thr His Lys Lys Phe Leu Cys Asp Arg Thr Met Trp850 855 860Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp865 870 875 880Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ser His Ala Leu Asp Met885 890 895Thr Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu900 905 910Phe Glu Val Phe Asp Val Val Arg Ala His Gln Pro His Arg Gly Val915 920 925Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr930 935 940Thr9452101072112877212DNA213黑猩猩腺病毒-ChAd 31六鄰體
400107atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300tttgacatcc gcggggtgct ggaccggggc cccactttca agccttactc tggcaccgcc 360tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca attagaagaa 420gcccaggccg ctgtggaaga cgaagaatta gaagatgaag acgaggaacc acaggatgag 480gcacctgtga aaaaaaccca tgtatacgct caggctcccc tttctggaga agaaattact 540aaaaacggtt tgcaaatagg gtcagataac acagaagccc agtctaagcc catatatgca 600gatcctacat tccagcctga accccaaatc ggggaatccc agtggaatga ggcagatgct 660acagttgccg gcggtagagt gctaaagaaa tccactccca tgaagccatg ctatggttcc 720tatgcaagac ccacaaactc caatggaggt caaggtgtgc tggtggctga tgataagggg 780gttcttcaat ctaaagttga attgcaattt ttttcaaata ctactactct taatcagcgg 840gagggtaacg atacaaaacc aaaagtggtg ctgtatagcg aagatgtgca catggaaact 900ccagacaccc acatttctta caagcccaca aaaagcgatg acaattcaaa aatcatgctg 960ggtcagcagt ccatgcccaa cagacctaat tacatcggct tcagagacaa ctttatcggc 1020ctcatgtatt acaatagcac tggcaacatg ggagtgcttg caggtcaggc ctctcagttg 1080aatgcagtgg tggacttgca agacagaaac acagaactgt cctaccagct cttgcttgat 1140tccatgggtg acagaaccag atacttttcc atgtggaatc aggcagtgga cagttatgac 1200ccagatgtca gaattattga aaatcatgga actgaagacg agctccccaa ctattgtttc 1260cctctgggcg gcataggggt aactgacact taccaggcca ttaaaaccaa tggcaatggt 1320caagaaaacc caacctggga aaaagataca gagtttgcag accgcaatga aataggggtg 1380ggaaacaatt ttgctatgga gatcaacctc agtgccaacc tgtggagaaa cttcctgtac 1440tccaacgtgg cgctgtacct accagacaag cttaagtaca acccctccaa tgtggacatc 1500tctgacaacc ccaacaccta cgattacatg aacaagcgag tggtggcccc ggggctggtg 1560gactgctaca tcaacctggg cgcgcgctgg tcgctggact acatggacaa cgtcaacccc 1620ttcaaccacc accgcaatgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680tatgtgccct tccacatcca ggtgccccag aagttctttg ccatcaagaa cctcctcctc 1740ctgccgggct cctacaccta cgagtggaac ttcaggaagg atgtcaacat ggtcctccag 1800agctctctgg gtaacgatct cagggtggac ggggccagca tcaagttcga gagcatctgc 1860ctctacgcca ccttcttccc catggcccac aacacggcct ccacgctcga ggccatgctc 1920aggaacgaca ccaacgacca gtccttcaat gactaccttt ccgccgccaa catgctctac 1980
cccatacccg ccaacgccac caacgtcccc atctccatcc cctcgcgcaa ctgggcggcc 2040ttccgcggct gggccttcac ccgcctcaag accaaggaga ccccctccct gggctcggga 2100ttcgacccct actacaccta ctcgggctct attccctacc tggacggcac cttctacctc 2160aaccacactt tcaagaaggt ctcggtcacc ttcgactcct cggtcagctg gccgggcaac 2220gaccgtctgc tcacccccaa cgagttcgag atcaagcgct cggtcgacgg ggagggctac 2280aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggccaactac 2340aacatcggct accagggctt ctacatccca gagagctaca aggacaggat gtactccttc 2400ttcaggaact tccagcccat gagccggcag gtggtggacc agaccaagta caaggactac 2460caggaggtgg gcatcatcca ccagcacaac aactcgggct tcgtgggcta cctcgccccc 2520accatgcgcg agggacaggc ctaccccgcc aacttcccct acccgctcat aggcaagacc 2580gcggtcgaca gcatcaccca gaaaaagttc ctctgcgacc gcaccctctg gcgcatcccc 2640ttctccagca acttcatgtc catgggtgcg ctctcggacc tgggccagaa cttgctctac 2700gccaactccg cccacgccct cgacatgacc ttcgaggtcg accccatgga cgagcccacc 2760cttctctatg ttctgttcga agtctttgac gtggtccggg tccaccagcc gcaccgcggc 2820gtcatcgaga ccgtgtacct gcgtacgccc ttctcggccg gcaacgccac cacctaa2877210108211958212PRT213黑猩猩腺病毒-ChAd 31六鄰體400108Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala130 135 140Val Glu Asp Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu145 150 155 160Ala Pro Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly165 170 175Glu Glu Ile Thr Lys Asn Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu180185 190Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro195 200 205Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly210 215 220Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr Gly Ser225 230 235 240Tyr Ala Arg Pro Thr Asn Ser Asn Gly Gly Gln Gly Val Leu Val Ala245 250 255Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu Leu Gln Phe Phe Ser206 265 270Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly Asn Asp Thr Lys Pro Lys275 280 285Val Val Leu Tyr Ser Glu Asp Val His Me Glu Thr Pro Asp Thr His290 295 300Ile Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Ile Met Leu305 310 315320Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp325 330 335Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val340 345 350Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp355 360 365Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp370 375 380
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp385 390 395 400Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro405 410 415Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln420 425 430Ala Ile Lys Thr Asn Gly Asn Gly Gln Glu Asn Pro Thr Trp Glu Lys435 440 445Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe450 455 460Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe Leu Tyr465 470 475 480Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser485 490 495Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys500 505 510Arg Val Val Ala Pro Gly Leu Val Asp Cys TyrIle Asn Leu Gly Ala515 520 525Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His530 535 540Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg545 550 555 560Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys565 570 575Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg580 585 590Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg595 600 605Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr610 615 620Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu625 630 635 640Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala645 650 655
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser660 665 670Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg675 680 685Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr690 695 700Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu705 710 715 720Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser725 730 735Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys740 745 750Arg Ser Val Asp Gly Glu Gly Tyr Ash Val Ala Gln Cys Asn Met Thr755 760 765Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr770 775 780Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe785 790 795 800Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys805 810 815Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser820 825 830Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr835 840 845Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser850 855 860Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro865 870 875 880Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln885 890 895Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu900 905 910Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val915 920 925
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr930 935 940Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 9552101092112856212DNA213黑猩猩腺病毒-ChAd 37六鄰體400109atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120ctggggaaca agtttaggaa ccccaccgtg gcccctaccc acgatgtgac caccgaccgt 180agccagcggc tgatgctgcg ctttgtgccc gttgatcggg aggacaatac ctactcttac 240aaagttcgct acacactggc tgtgggcgac aacagagtgc tggacatggc cagcaccttc 300tttgacatca ggggggtgct tgacagaggt cccagtttca agccatactc tggcacagct 360tacaattccc tggcgcctaa gggcgcgccc aatacatgcc agtggattgc caagggggcg 420cctgttaccg atcaagacaa tgaagaacag gaattaacag atgttactta cgcttttggc 480aatgctccag tacaagcaga agccaaaatt acaaaagatg gtctgccagt aggtttggaa 540attacagaag atgaacaaaa gtcaatttat gcagacaaat tgtatcagcc agagccccaa 600attggcgatg aacaatggca tgacaccact ggcactaatg aacaatacgg cggcagagct 660ctaaaaccgg ccaccaacat gaaaccatgt tatggctcat ttgccagacc cacaaataaa 720aaaggcggtc aggctaaaac tagaaaaata gaaaaggaag agaatggagt taaaaccgta 780actgaagaag ctgacattga tatggacttt tatgacttaa gatcacaaag agcaaatttt 840gatcctaaaa ttgttcttta ttctgaaaat gtaaatttgg aaactccaga tacacatatt 900gtgtataaac caggaacaga tgaaactagt tcctctgtta acttgggaca gcaggcaatg 960cccaacagac ccaactacat tggttttagg gacaacttca ttggacttat gttttacaac 1020agtaccggca acatgggcgt gctggccggg caagcttctc agttaaatgc tgtggttgac 1080ttgcaggaca ggaacacaga actgtcctac cagctgctgc ttgactctct gggtgacaga 1140accagatact ttagcatgtg gaatcaggcc gtggatagct atgacccaga cgtgcgcatt 1200attgaaaacc acggtgtgga agacgaactt cctaactatt gttttccatt agatggagtg 1260ggaccaatta cgggcactta tcagggggtt gagcctgatg gaaacaatgg aaactggaag 1320aaaaacacaa acataaatgg agcaaatgaa attggcaagg gaaataacta tgctatggaa 1380
attaatctac aagctaacct ctggagaagt tttctatatt ccaatgtggc tctgtattta 1440ccagacggtt acaaatatac cccagccaat gttacactgc cagaaaacaa aaacacctat 1500ggctatataa acggacgagt agtatcccca tctttggtgg attcatacat caacattgga 1560gccagatggt ctttggatct tatggacaat gtaaacccat tcaatcacca ccgcaatgca 1620ggcctgcgtt accgttccat gcttttagga aatggtcgct atgtgccttt ccacatccaa 1680gtgcctcaga aaatctttgc tgtcaagaac ctgttgcttc ttcccggctc ctacacctat 1740gagtggaact tcagaaagga cgtaaacatg gtcctgcaaa gttcccttgg taatgatctc 1800agaactgatg gtgctagcat cagttttacc agcatcaatc tatatgctac ctttttcccc 1860atggcccaca acactgcttc cacccttgaa gccatgctgc gcaatgacac caatgaccag 1920tcatttaatg actacctttc tgcagctaac atgctctacc ctattccagc caatgcaacc 1980aacatcccca tttccattcc ctctcgcaat tgggccgcct tcaggggctg gtccttcacc 2040agactcaaaa ccaaggagac cccatctctg ggatcagggt tcgatcccta ctttgtctat 2100tctggttcta ttccctacct tgatggcacc ttctacctta accacacttt caagaaggtc 2160tccatcatgt ttgactcctc agtcagctgg ccaggcaatg acaggcttct aactccaaat 2220gagtttgaaa tcaaacgcac tgtggatggg gaagggtaca atgtggctca atgcaacatg 2280accaaggact ggttcctggt tcaaatgctc gccaactaca acattggcta ccagggcttc 2340tacatcccag aggggtacaa ggatcgcatg tactccttct tcagaaactt ccagcccatg 2400agtaggcagg tggttgatga gatcaactac aaggagtacc aagctgtcac acttgcttac 2460cagcacaaca actctggctt tgtgggttac catgcaccca ctctccgtca gggtcaacca 2520tacccagcta actacccata cccgcttatt ggaaccactg ctgtcaccag cgtcacccag 2580aaaaagttct tgtgcgacag gaccatgtgg cgcatcccct tctccagcaa cttcatgtcc 2640atgggtgccc ttaccgacct ggggcagaac atgctttatg ctaactcagc tcatgcgctg 2700gacatgactt ttgaggtgga tcccatggat gagcccacac tgctttatct tcttttcgaa 2760gtcttcgacg tggtcagagt gcaccagcca caccgcggcg tcatcgaggc cgtctacctg 2820cgcacaccgt tctcggccgg caacgccacc acataa 2856210110211951212PRT213黑猩猩腺病毒-ChAd 37六鄰體400110Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Ile Ala Lys Gly Ala Pro Val Thr Asp130 135 140Gln Asp Asn Glu Glu Gln Glu Leu Thr Asp Val Thr Tyr Ala Phe Gly145 150 155 160Asn Ala Pro Val Gln Ala Glu Ala Lys Ile Thr Lys Asp Gly Leu Pro165 170 175Val Gly Leu Glu Ile Thr Glu Asp Glu Gln Lys Ser Ile Tyr Ala Asp180 185 190Lys Leu Tyr Gln Pro Glu Pro Gln Ile Gly Asp Glu Gln Trp His Asp195 200 205Thr Thr Gly Thr Asn Glu Gln Tyr Gly Gly Arg Ala Leu Lys Pro Ala210 215 220Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys225 230 235 240Lys Gly Gly Gln Ala Lys Thr Arg Lys Ile Glu Lys Glu Glu Asn Gly245 250 255Val Lys Thr Val Thr Glu Glu Ala Asp Ile Asp Met Asp Phe Tyr Asp260 265 270Leu Arg Ser Gln Arg Ala Asn Phe Asp Pro Lys Ile Val Leu Tyr Ser275 280 285Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Pro290 295 300
Gly Thr Asp Glu Thr Ser Ser Ser Val Asn Leu Gly Gln Gln Ala Met305 310 315 320Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu325 330 335Met Phe Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala340 345 350Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu355 360 365Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe370 375 380Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile385 390 395 400Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro405 410 415Leu Asp Gly Val Gly Pro Ile Thr Gly Thr Tyr Gln Gly Val Glu Pro420 425 430Asp Gly Asn Asn Gly Asn Trp Lys Lys Asn Thr Asn Ile Asn Gly Ala435 440 445Asn Glu Ile Gly Lys Gly Asn Asn Tyr Ala Met Glu Ile Asn Leu Gln450 455 460Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu465 470 475 480Pro Asp Gly Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu Pro Glu Asn485 490 495Lys Asn Thr Tyr Gly Tyr Ile Asn Gly Arg Val Val Ser Pro Ser Leu500 505 510Val Asp Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Leu Met515 520 525Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr530 535 540Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln545 550 555 560Val Pro Gln Lys Ile Phe Ala Val Lys Asn Leu Leu Leu Leu Pro Gly565 570 575
Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Val Leu580 585 590Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser595 600 605Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn610 615 620Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln625 630 635 640Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro645 650 655Ala Asn Ala Thr Asn Ile Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala660 665 670Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro675 680 685Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile690 695 700Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val705 710 715 720Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu725 730 735Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly740 745 750Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln755 760 765Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Ile Pro Glu770 775 780Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met785 790 795 800Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys Glu Tyr Gln Ala Val805 810 815Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr His Ala820 825 830Pro Thr Leu Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro835 840 845
Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu850 855 860Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser865 870 875 880Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser885 890 895Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met Asp Glu Pro900 905 910Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp Val Val Arg Val His915 920 925Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe930 935 940Ser Ala Gly Asn Ala Thr Thr945 9502101112112817212DNA213黑猩猩腺病毒-ChAd 38六鄰體400111atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360tacaacgccc tggcccctaa agccgctcct aatcctagcc agtgggagga aaccactact 420ggaacggatg gaaatgctgc tactacaact acacatagtt ttggcctggc tgctatgaaa 480ggggacaata ttacatctga cggtttgcaa ataggaacag atgctacttc tggagaggaa 540aaacccatct atgcagataa actgtaccag ccagaacccc aaatagggga agagtcatgg 600actgatactg atggaaccaa tgaaaaattc ggaggaagag tccttaaaaa ggacacaagc 660atgaaaccct gctacgggtc atttgccaaa ccaaccaata acaaaggtgg tcaagcaaaa 720caaaaggcaa ctgaaggaac cgctgtagaa tatgatgtag acatgaactt ttttgatggt 780agagatgcag ctgctaactt tactccagaa gtagtgttgt atgctgaaaa tgtggatttg 840
gaaactccag atacacatat tgtatacaaa ccaggaacct cagatgtgag ttcccatgtt 900aatttgggac agcaagccat gcccaacaga cccaactaca ttggtttcag agacaacttt 960attggtctca tgtattacaa cagcactggc aatatggggg tgctggccgg tcaggcttct 1020cagctgaatg ctgtggttga cttgcaagac agaaacactg aactgtccta ccagctgttg 1080cttgactctt tgggtgacag aactcggtat ttcagtatgt ggaatcaggc ggtggacagc 1140tatgatcctg atgtgcgcat cattgaaaat catggtatag aagatgagct tcccaactat 1200tgctttccta ttgacgctgt gggtattact agaacttatc aaggtatcaa aacgcaaaat 1260ggtcaaacta caacttggga aaaggacacc agtgttagta cggccaatga aataggcatt 1320ggcaacaatc ttgccatgga aatcaacatc caagccaacc tgtggaggaa cttcctctac 1380gccaacgtgg ccctgtacct gcccgattct tacaagtaca caccggccaa cgtcaccctg 1440cccaccaata ccaacaccta cgattacatg aacggccggg tggtggcgcc ctcgctggtg 1500gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggataa cgtgaatccc 1560ttcaaccacc accgcaacgc ggggctgcgc taccgctcca tgctcctggg caacgggcgc 1620tacgtgccct tccacatcca ggtgccccag aaatttttcg ccatcaagag cctcctgctc 1680ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat gatcctgcag 1740agctccctcg gcaacgacct gcgcacggac ggggcctcca tctccttcac cagcatcaac 1800ctctacgcca ccttcttccc catggcgcac aacacggcct ccacgctcga ggccatgctg 1860cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa catgctctac 1920cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa ctgggccgcc 1980ttccgcggct ggtccttcac gcgcctcaag accaaggaga cgccctcgct gggctccggg 2040ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac cttctacctc 2100aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg gcccggcaac 2160gaccggctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg cgagggctac 2220aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggcccactac 2280aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat gtactccttc 2340ttccgcaact tccaacccat gagccgccag gtggtggacg aggtcaacta caaggactac 2400caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta cctcgcgccc 2460accatgcgcc agggccagcc ctaccccgcc aactacccct acccgctcat cggcaagagc 2520gccgtcacca gcgtcaccca gaaaaagttc ctctgcgaca gggtcatgtg gcgcatcccc 2580ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa catgctctat 2640gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga tgagtccacc 2700cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc ccaccgcggc 2760gtcatcgagg ccgtctacct gcgcaccccc ttctcggccg gtaacgccac cacctaa2817210112
211938212PRT213黑猩猩腺病毒-ChAd 38六鄰體400112Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ala Leu Ala Pro Lys Ala115 120 125Ala Pro Asn Pro Ser Gln Trp Glu Glu Thr Thr Thr Gly Thr Asp Gly130 135 140Asn Ala Ala Thr Thr Thr Thr His Ser Phe Gly Leu Ala Ala Met Lys145 150 155 160Gly Asp Asn Ile Thr Ser Asp Gly Leu Gln Ile Gly Thr Asp Ala Thr165 170 175Ser Gly Glu Glu Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln Pro Glu180 185 190Pro Gln Ile Gly Glu Glu Ser Trp Thr Asp Thr Asp Gly Thr Asn Glu195 200 205Lys Phe Gly Gly Arg Val Leu Lys Lys Asp Thr Ser Met Lys Pro Cys210 215 220Tyr Gly Ser Phe Ala Lys Pro Thr Asn Asn Lys Gly Gly Gln Ala Lys225 230 235 240
Gln Lys Ala Thr Glu Gly Thr Ala Val Glu Tyr Asp Val Asp Met Asn245 250 255Phe Phe Asp Gly Arg Asp Ala Ala Ala Asn Phe Thr Pro Glu Val Val260 265 270Leu Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr His Ile Val275 280 285Tyr Lys Pro Gly Thr Ser Asp Val Ser Ser His Val Asn Leu Gly Gln290 295 300Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe305 310 315 320Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala325 330 335Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn340 345 350Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr355 360 365Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp370 375 380Val Arg Ile Ile Glu Asn His Gly Ile Glu Asp Glu Leu Pro Asn Tyr385 390 395 400Cys Phe Pro Ile Asp Ala Val Gly Ile Thr Arg Thr Tyr Gln Gly Ile405 410 415Lys Thr Gln Asn Gly Gln Thr Thr Thr Trp Glu Lys Asp Thr Ser Val420 425 430Ser Thr Ala Asn Glu Ile Gly Ile Gly Asn Asn Leu Ala Met Glu Ile435 440 445Asn Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala450 455 460Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu465 470 475 480Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala485 490 495Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu500 505 510
Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly515 520 525Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe530 535 540His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu545 550 555 560Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn565 570 575Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala580 585 590Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met595 600 605Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr610 615 620Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr625 630 635 640Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg645 650 655Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys660 665 670Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser675 680 685Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe690 695 700Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn705 710 715 720Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp725 730 735Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe740 745 750Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr755 760 765Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe770 775 780
Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr785 790 795 800Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly805 810 815Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr820 825 830Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys835 840 845Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn850 855 860Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr865 870 875 880Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met885 890 895Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val900 905 910Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg915 920 925Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 9352101132112781212DNA213黑猩猩腺病毒-ChAd 44六鄰體400113atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggcccccaa gggagcgccc aatcccagcc agtgggaaca aactgaaacc 420aatgttaata aaacacacac cttcggaatg gcagccatga aaggagaggc tattgacaaa 480aatggtctgc aaattggaac tgacgctgcg gatcaggata aaccaattta tgcagataaa 540acattccagc ctgaacctca agtaggagag gaagactgga ttgacaaagc agatttttat 600ggcggaagag ctcttaaaaa agataccaag atgaaaccat gctatggctc atttgccaaa 660cctacaaatg tcaagggagg acaggcaacg cccaggacta aagcagatgg aactactgag 720cctgatattg acatgaactt ctttgaccca accactatta acacaccaga tgtagtgttg 780tatgctgaaa atgttgattt gcaaactcca gacacccata tagtttacaa agcaggaact 840tcagatgaca gttctgaggt caatttggct cagcaagcta tgcctaacag gcccaactac 900attggtttca gagacaactt tatcggactt atgtattaca atagcactgg caatatgggt 960gtgctcgctg gtcaggcttc ccagctaaat gctgtggtgg acttgcaaga cagaaacacc 1020gagctgtcct accagctctt gcttgactct ctgggtgaca gaaccaggta tttcagtatg 1080tggaatcagg cggtggacag ctatgatcct gatgtgcgca ttattgaaaa ccatggtgtg 1140gaggatgaac tgccaaacta ttgctttcct ttggatggtg tgggcactaa taccgcatac 1200caaggcgtta aagttaagac aactaatgga aacgacacgt gggaaaaaga tgaaactgtt 1260tatgagttta atcaaattgg aaagggggat atctatgcta tggaaatcaa cattcaagcc 1320aacctgtgga gaagttttct ctactcgaac gtggccctgt acctgcccga ttcttacaag 1380tacacgccgg ccaacgtcac cctgcccacc aacaccaaca cctacgatta catgaacggg 1440agagtggtgc ctccctcgct ggtggacgcc tacatcaaca tcggggcgcg ctggtcgctg 1500gaccccatgg acaacgtgaa ccccttcaac caccaccgca acgcggggct gcgctaccgc 1560tccatgctcc tgggcaacgg gcgcttcgtg cccttccaca tccaggtgcc ccagaaattt 1620ttcgccatca agagcctcct gctcctgcca gggtcctaca cctacgagtg gaacttccgc 1680aaggacgtca acatgatcct gcagagctcc ctcggcaacg acctgcgcac ggacggggcc 1740tccatctcct tcaccagtat caacctctac gccaccttct tccccatggc gcacaacacg 1800gcctccacgc tcgaggccat gctgcgcaac gacaccaacg accagtcctt caacgactac 1860ctctcggcgg ccaacatgct ctaccccatc ccggccaacg ccaccaacgt gcccatctcc 1920atcccctcgc gcaactgggc cgccttccgc ggctggtcct tcacgcgcct caagaccaag 1980gagacgccct cgctgggctc cgggttcgac ccctacttcg tctactcggg ctccatcccc 2040tacctcgacg gcaccttcta cctcaaccac accttcaaga aggtctccat caccttcgac 2100tcctccgtca gctggcccgg caacgaccgc ctcctgacgc ccaacgagtt cgaaatcaag 2160cgcaccgtcg acggagaggg gtacaacgtg gcccagtgca acatgaccaa ggactggttc 2220ctggtccaga tgctggccca ctacaacatc ggctaccagg gcttctacgt gcccgagggc 2280tacaaggacc gcatgtactc cttcttccgc aacttccagc ccatgagccg ccaggtggtg 2340gacgaggtca actacaagga ctaccaggcc gtcaccctgg cctaccagca caacaactcg 2400ggcttcgtcg gctacctcgc gcccaccatg cgccagggcc agccctaccc cgccaactac 2460
ccgtacccgc tcatcggcaa gagcgccgtc accagcgtca cccagaaaaa gttcctctgc 2520gacagggtca tgtggcgcat ccccttctcc agcaacttca tgtccatggg cgcgctcacc 2580gacctcggcc agaacatgct ctatgccaac tccgcccacg cgctagacat gaatttcgaa 2640gtcgacccca tggatgagtc cacccttctc tatgttgtct tcgaagtctt cgacgtcgtc 2700cgagtgcacc agccccaccg cggcgtcatc gaggccgtct acctgcgcac ccccttctcg 2760gccggtaacg ccaccaccta a 2781210114211926212PRT213黑猩猩腺病毒-ChAd 44六鄰體400114Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Pro Ser Gln Trp Glu Gln Thr Glu Thr Asn Val Asn Lys130 135 140Thr His Thr Phe Gly Met Ala Ala Met Lys Gly Glu Ala Ile Asp Lys145 150 155 160Asn Gly Leu Gln Ile Gly Thr Asp Ala Ala Asp Gln Asp Lys Pro Ile165 170 175
Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val Gly Glu Glu Asp180 185 190Trp Ile Asp Lys Ala Asp Phe Tyr Gly Gly Arg Ala Leu Lys Lys Asp195 200 205Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val210 215 220Lys Gly Gly Gln Ala Thr Pro Arg Thr Lys Ala Asp Gly Thr Thr Glu225 230 235 240Pro Asp Ile Asp Met Asn Phe Phe Asp Pro Thr Thr Ile Asn Thr Pro245 250 255Asp Val Val Leu Tyr Ala Glu Asn Val Asp Leu Gln Thr Pro Asp Thr260 265 270His Ile Val Tyr Lys Ala Gly Thr Ser Asp Asp Ser Ser Glu Val Asn275 280 285Leu Ala Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg290 295 300Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly305 310 315 320Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln325 330 335Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly340 345 350Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr355 360 365Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu370 375 380Pro Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Thr Asn Thr Ala Tyr385 390 395 400Gln Gly Val Lys Val Lys Thr Thr Asn Gly Asn Asp Thr Trp Glu Lys405 410 415Asp Glu Thr Val Tyr Glu Phe Asn Gln Ile Gly Lys Gly Asp Ile Tyr420 425 430Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr435 440 445
Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala450 455 460Asn Val Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly465 470 475 480Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala485 490 495Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His500 505 510Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg515 520 525Phe Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys530 535 540Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg545 550 555 560Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg565 570 575Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr580 585 590Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu595 600 605Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala610 615 620Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser625 630 635 640Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg645 650 655Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr660 665 670Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu675 680 685Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser690 695 700Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys705 710 715 720
Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr725 730 735Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr740 745 750Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe755 760 765Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn770 775 780Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser785 790 795 800Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr805 810 815Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser820 825 830Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro835 840 845Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln850 855 860Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu865 870 875 880Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val885 890 895Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala900 905 910Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr915 920 9252101152112877212DNA213黑猩猩腺病毒-ChAd 63六鄰體400115
atgtatgtcc gccgaccaga aggaggaaga ggcgcgtcgc cgagttgcaa gatggccacc 60ccatcgatgc tgccccagtg ggcgtacatg cacatcgccg gacaggacgc ttcggagtac 120ctgagtccgg gtctggtgca gttcgcccgc gccacagaca cctacttcag tctggggaac 180aagtttagga accccacggt ggcgcccacg cacgatgtga ccaccgaccg cagccagcgg 240ctgacgctgc gcttcgtgcc cgtggaccgc gaggacaaca cctactcgta caaagtgcgc 300tacacgctgg ccgtgggcga caaccgcgtg ctggacatgg ccagcaccta ctttgacatc 360cgcggcgtgc tggatcgggg ccccagcttc aaaccctact ccggcaccgc ctacaacagc 420ctagctccca agggagcgcc caacacctca cagtggaagg attccgacag caaaatgcat 480acttttggag ttgctgccat gcccggtgtt gttggtaaaa aaatagaagc cgatggtctg 540cctattggaa tagattcatc ctctggaact gacaccataa tttatgctga taaaactttc 600caaccagagc cacaggttgg aagtgacagt tgggtcgaca ccaatggtgc agaggaaaaa 660tatggaggta gagctcttaa ggacactaca aacatgaagc cctgctacgg ttcttttgcc 720aggcctacca acaaagaagg tggacaggct aacataaaag attctgaaac tgccagcact 780actcctaact atgatataga tttggcattc tttgacagca aaaatattgc agctaactac 840gatccagata ttgtaatgta cacagaaaat gttgagttgc aaactccaga tactcatatt 900gtgtttaagc caggaacttc agatgaaagt tcagaagcca atttgggcca gcaggccatg 960cccaacagac ccaactacat cgggttcaga gacaacttta tcgggctcat gtactacaac 1020agcactggca atatgggtgt actggctggt caggcctccc agctaaatgc tgtggtggac 1080ttgcaggaca gaaacaccga actgtcctac cagctcttgc ttgactctct gggtgacaga 1140accaggtatt tcagtatgtg gaatcaggcg gtggacagct atgaccccga tgtgcgcatt 1200attgaaaatc acggtgtgga ggatgaactc cccaattatt gcttcccttt gaatggtgta 1260ggctttacag atacttacca gggtgttaaa gttaagacag atacagccgc tactggtacc 1320aatggaacgc agtgggacaa agatgatacc acagtcagca ctgccaatga gatccactca 1380ggcaatcctt tcgccatgga gatcaacatc caggccaacc tgtggcggaa cttcctctac 1440gcgaacgtgg cgctgtacct gcccgactcc tacaagtaca cgccggccaa catcacgctg 1500ccgaccaaca ccaacaccta cgattacatg aacggccgcg tggtggcgcc ctcgctggtg 1560gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggacaa cgtcaacccc 1620ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680tacgtgccct tccacatcca ggtgccccaa aagtttttcg ccatcaagag cctcctgctc 1740ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat gatcctgcag 1800agctccctcg gcaacgacct gcgcacggac ggggcctcca tcgccttcac cagcatcaac 1860ctctacgcca ccttcttccc catggcgcac aacaccgcct ccacgctcga ggccatgctg 1920cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa catgctctac 1980cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa ctgggccgcc 2040ttccgcggat ggtccttcac gcgcctcaag acccgcgaga cgccctcgct cggctccggg 2100
ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac cttctacctc 2160aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg gcccggcaac 2220gaccgcctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg agagggatac 2280aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggcccactac 2340aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat gtactccttc 2400ttccgcaact tccagcccat gagccgccag gtcgtggacg aggtcaacta caaggactac 2460caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta cctcgcgccc 2520accatgcgcc agggccagcc ctaccccgcc aactacccct acccgctcat cggcaagagc 2580gccgtcgcca gcgtcaccca gaaaaagttc ctctgcgacc gggtcatgtg gcgcatcccc 2640ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa catgctctac 2700gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga tgagtccacc 2760cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc ccaccgcggc 2820gtcatcgagg ccgtctacct gcgcacgccc ttctcggccg gcaacgccac cacctaa2877210116211941212PRT213黑猩猩腺病毒-ChAd 63六鄰體400 116Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125Ala Pro Asn Thr Ser Gln Trp Lys Asp Ser Asp Ser Lys Met His Thr130 135 140Phe Gly Val Ala Ala Met Pro Gly Val Val Gly Lys Lys Ile Glu Ala145 150 155 160Asp Gly Leu Pro Ile Gly Ile Asp Ser Ser Ser Gly Thr Asp Thr Ile165 170 175Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val Gly Ser Asp180 185 190Ser Trp Val Asp Thr Asn Gly Ala Glu Glu Lys Tyr Gly Gly Arg Ala195 200 205Leu Lys Asp Thr Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg210 215 220Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Ile Lys Asp Ser Glu Thr225 230 235 240Ala Ser Thr Thr Pro Asn Tyr Asp Ile Asp Leu Ala Phe Phe Asp Ser245 250 255Lys Asn Ile Ala Ala Asn Tyr Asp Pro Asp Ile Val Met Tyr Thr Glu260 265 270Asn Val Glu Leu Gln Thr Pro Asp Thr His Ile Val Phe Lys Pro Gly275 280 285Thr Ser Asp Glu Ser Ser Glu Ala Asn Leu Gly Gln Gln Ala Met Pro290 295 300Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met305 310 315 320Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser325 330 335Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser340 345 350Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser355 360 365Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile370 375 380Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu385 390 395 400
Asn Gly Val Gly Phe Thr Asp Thr Tyr Gln Gly Val Lys Val Lys Thr405 410 415Asp Thr Ala Ala Thr Gly Thr Asn Gly Thr Gln Trp Asp Lys Asp Asp420 425 430Thr Thr Val Ser Thr Ala Asn Glu Ile His Ser Gly Asn Pro Phe Ala435 440 445Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala450 455 460Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn465 470 475 480Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg485 490 495Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg500 505 510Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg515 520 525Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr530 535 540Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser545 550 555 560Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys565 570 575Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr580 585 590Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe595 600 605Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg610 615 620Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn625 630 635 640Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile645 650 655Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu660 665 670
Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe675 680 685Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn690 695 700His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp705 710 715 720Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg725 730 735Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys740 745 750Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln755 760 765Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe770 775 780Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr785 790 795 800Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly805 810 815Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro820 825 830Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val835 840 845Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe850 855 860Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn865 870 875 880Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val885 890 895Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe900 905 910Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val915 920 925Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935 940
2101172112811212DNA213黑猩猩腺病毒-ChAd 82六鄰體400117atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacttac 300tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaatgaaaac 420aatggtcaag gtcaagctaa gacacacacc tatggtgttg ctgctatggg cggacttgat 480attacaaaag agggtcttaa aattgtaact gatgctagta aggaagatga caatgaaatt 540tatgcagata aaacatatca gcccgagcct caaataggag aggaaaattg gcaagacact 600aaaaactttt atggaggcag agctcttaaa aaagatacca agatgaagcc atgctatggc 660tcatttgcca gacctaccaa tgtgaaggga gggcaagcca aagtgaaaac agaagaaaat 720gttcagtcat ttgacataga tctggctttc tttgatattc caagcaccgg cacagggggc 780aatggtacaa atgtaaatga taagccagac atggttatgt acactgaaaa tgtgaatctg 840gagacgccag atactcatat tgtgtacaaa cctggaactt cagatgacag ctctgaagcc 900aacttgtgcc agcaggccat gccaaacaga cccaactaca ttggtttcag agacaacttt 960attgggctca tgtattacaa cagtactggc aatatggggg tgctggctgg tcaggcctcc 1020cagctgaatg ctgtggttga cttgcaagac agaaacaccg agctgtcata ccagctcttg 1080cttgactctc tgggtgacag aacccggtat ttcagcatgt ggaaccaggc ggtggacagt 1140tatgaccctg atgtgcgcat tattgaaaac catggtgtgg aggatgaatt gccaaactat 1200tgcttcccct tggatggagc tggcactaat gctgtatacc ggggtgttaa agcaaaagat 1260aacggaaact gggaacaaga cacaggcgtt tcaagtatta accagatatg caaggggaac 1320atctatgcca tggaaatcaa cattcaagcc aacctgtgga gaagtttcct ttactcgaac 1380gtggccctgt acctgcccga ctcttacaag tacacgccgg ccaacatcac cctgcccacc 1440aacaccaaca cctacgatta catgaacggt cgggtggtgc ctccctcgct ggtggacgcc 1500tacatcaaca tcggggcgcg ctggtcgctg gaccccatgg acaacgtcaa tcccttcaac 1560caccaccgca acgcgggcct gcgctaccgc tccatgctcc tgggcaacgg gcgctacgtg 1620
cccttccaca tccaggtgcc ccagaaattt ttcgccatca agagcctcct gctcctgccc 1680gggtcctaca cctacgagtg gaacttccgc aaggacgtca acatgatcct gcagagctcc 1740ctcggcaacg acctgcgcac ggacggggcc tccatctcct tcaccagcat caacctctac 1800gccaccttct tccccatggc gcacaacacg gcctccacgc tcgaggccat gctgcgcaac 1860gacaccaacg accagtcctt caacgactac ctctcggcgg ccaacatgct ctaccccatc 1920ccggccaacg ccaccaacgt gcccatctcc atcccctcgc gcaactgggc cgccttccgc 1980ggctggtcct tcacgcgtct caagaccaag gagacgccct cgctgggctc cgggttcgac 2040ccctacttcg tctactcggg ctccatcccc tacctcgacg gcaccttcta cctcaaccac 2100accttcaaga aggtctccat caccttcgac tcctccgtca gctggcccgg caacgaccgg 2160ctcctgacgc ccaacgagtt cgaaatcaag cgcaccgtcg acggcgaggg ctacaacgtg 2220gcccagtgca acatgaccaa ggactggttc ctggtccaga tgctggccca ctacaacatc 2280ggctaccagg gcttctacgt gcccgagggc tacaaggacc gcatgtactc cttcttccgc 2340aacttccagc ccatgagccg ccaggtggtg gacgaggtca actacaagga ctaccaggcc 2400gtcaccctgg cctaccagca caacaactcg ggcttcgtcg gctacctcgc gcccaccatg 2460cgccaggggc agccctaccc cgccaactac ccgtacccgc tcatcggcaa gagcgccgtc 2520accagcgtca cccagaaaaa gttcctctgc gacagggtca tgtggcgcat ccccttctcc 2580agcaacttca tgtccatggg cgcgctcacc gacctcggcc agaacatgct ctatgccaac 2640tccgcccacg cgctagacat gaatttcgaa gtcgacccca tggatgagtc cacccttctc 2700tatgttgtct tcgaagtctt cgacgtcgtc cgagtgcacc agccccaccg cggcgtcatc 2760gaggccgtct acctgcgcac acccttctcg gccggtaacg ccaccaccta a 2811210118211936212PRT213黑猩猩腺病毒-ChAd 82六鄰體400118Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Ser Gln Trp Glu Gln Asn Glu Asn Asn Gly Gln Gly130 135 140Gln Ala Lys Thr His Thr Tyr Gly Val Ala Ala Met Gly Gly Leu Asp145 150 155 160Ile Thr Lys Glu Gly Leu Lys Ile Val Thr Asp Ala Ser Lys Glu Asp165 170 175Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Ile180 185 190Gly Glu Glu Asn Trp Gln Asp Thr Lys Asn Phe Tyr Gly Gly Arg Ala195 200 205Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg210 215 220Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Val Lys Thr Glu Glu Asn225 230 235 240Val Gln Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro Ser Thr245 250 255Gly Thr Gly Gly Asn Gly Thr Asn Val Asn Asp Lys Pro Asp Met Val260 265 270Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val275 280 285Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Glu Ala Asn Leu Cys Gln290 295 300Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe305 310 315 320Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala325 330 335
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn340 345 350Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr355 360 365Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp370 375 380Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr385 390 395 400Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ala Val Tyr Arg Gly Val405 410 415Lys Ala Lys Asp Asn Gly Asn Trp Glu Gln Asp Thr Gly Val Ser Ser420 425 430Ile Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met Glu Ile Asn Ile435 440 445Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr450 455 460Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr465 470 475 480Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Pro Pro Ser485 490 495Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro500 505 510Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg515 520 525Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile530 535 540Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro545 550 555 560Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile565 570 575Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile580 585 590Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His595 600 605
Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp610 615 620Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile625 630 635 640Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp645 650 655Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr660 665 670Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser675 680 685Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys690 695 700Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg705 710 715 720Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu725 730 735Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val740 745 750Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro755 760 765Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro770 775 780Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala785 790 795 800Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu805 810 815Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr820 825 830Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys Lys Phe835 840 845Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met850 855 860Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn865 870 875 880
Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu885 890 895Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val900 905 910His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro915 920 925Phe Ser Ala Gly Asn Ala Thr Thr930 935210119211933212PRT213黑猩猩腺病毒-CV23 Pan5六鄰體400119Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Asp Gly Asp Thr Gly130 135 140Thr Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser
l45 150 155 160Ile Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro165 170 175Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala180 185 190Glu Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala195 200 205Leu Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys210 215 220Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly225 230 235 240Gly Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser245 250 255Ala Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn260 265 270Val Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr275 280 285Asp Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn290 295 300Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr305 310 315 320Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln325 330 335Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr340 345 350Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met355 360 365Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu370 375 380Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp385 390 395 400Ala Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Ala405 410 415Asp Gln Thr Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu420 425 430
Leu Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn435 440 445Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp450 455 460Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn465 470 475 480Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp485 490 495Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn500 505 510Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser515 520 525Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro530 535 540Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr545 550 555 560Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser565 570 575Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr580 585 590Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala595 600 605Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe610 615 620Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn625 630 635 640Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe645 650 655Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu660 665 670Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr675 680 685Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile690 695 700
Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr705 710 715 720Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Ash725 730 735Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu740 745 750Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr755 760 765Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg770 775 780Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu785 790 795 800Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr805 810 815Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile820 825 830Gly Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp835 840 845Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly850 855 860Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His865 870 875 880Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu885 890 895Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro900 905 910His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala915 920 925Gly Asn Ala Thr Thr930210120211942
212PRT213黑猩猩腺病毒-CV32 Pan6六鄰體400120Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asn Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Val Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Ash Ser Ser Gln Trp Glu Gln Ala Lys Thr Gly Asn Gly Gly130 135 140Thr Met Glu Thr His Thr Tyr Gly Val Ala Pro Met Gly Gly Glu Asn145 150 155 160Ile Thr Lys Asp Gly Leu Gln Ile Gly Thr Asp Val Thr Ala Asn Gln165 170 175Asn Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val180 185 190Gly Glu Glu Asn Trp Gln Glu Thr Glu Asn Phe Tyr Gly Gly Arg Ala195 200 205Leu Lys Lys Asp Thr Asn Met Lys Pro Cys Tyr Gly Ser Tyr Ala Arg210 215 220Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Leu Lys Val Gly Asp Asp225 230 235 240
Gly Val Pro Thr Lys Glu Phe Asp Ile Asp Leu Ala Phe Phe Asp Thr245 250 255Pro Gly Gly Thr Val Asn Gly Gln Asp Glu Tyr Lys Ala Asp Ile Val260 265 270Met Tyr Thr Glu Asn Thr Tyr Leu Glu Thr Pro Asp Thr His Val Val275 280 285Tyr Lys Pro Gly Lys Asp Asp Ala Ser Ser Glu Ile Asn Leu Val Gln290 295 300Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe305 310 315 320Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala325 330 335Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn340 345 350Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr355 360 365Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp370 375 380Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr385 390 395 400Cys Phe Pro Leu Asp Gly Ser GlyThr Asn Ala Ala Tyr Gln Gly Val405410 415Lys Val Lys Asp Gly Gln Asp Gly Asp Val Glu Ser Glu Trp Glu Asn420 425 430Asp Asp Thr Val Ala Ala Arg Asn Gln Leu Cys Lys Gly Asn Ile Phe435 440 445Ala Met Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr450 455 460Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Thr465 470 475 480Asn Val Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly485 490 495Arg Val Thr Pro Pro Ser Leu Val Asp Ala Tyr Leu Asn Ile Gly Ala500 505 510
Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His515 520 525Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg530 535 540Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys545 550 555 560Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg565 570 575Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg580 585 590Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr595 600 605Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu610 615 620Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala625 630 635 640Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser645 650 655Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg660 665 670Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr675 680 685Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu690 695 700Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser705 710 715 720Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys725 730 735Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr740 745 750Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr755 760 765Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe770 775 780
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn785 790 795 800Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser805 810 815Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr820 825 830Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser835 840 845Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro850 855 860Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln865 870 875 880Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu885 890 895Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val900 905 910Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala915 920 925Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935 940210121211932212PRT213黑猩猩腺病毒-CV33 Pan7六鄰體400121Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Gly Asp Thr Asp Thr130 135 140Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser Ile145 150 155 160Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Ser Asp Gly Gln Ala Ile165 170 175Tyr Ala Asp Glu Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala Glu180 185 190Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala Leu195 200 205Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro210 215 220Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly Gly225 230 235 240Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser Ala245 250 255Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn Val260 265 270Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp275 280 285Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg290 295 300Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr305 310 315 320
Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu325 330 335Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln340 345 350Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp355 360 365Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn370 375 380His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Ala385 390 395 400Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Asp Asn405 410 415Gln Thr Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu Leu420 425 430Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu435 440 445Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser450 455 460Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr465 470 475 480Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala485 490 495Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val500 505 510Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met515 520 525Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln530 535 540Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr545 550 555 560Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser565 570 575Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser580 585 590
Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser595 600 605Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn610 615 620Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala625 630 635 640Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg645 650 655Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly660 665 670Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu675 680 685Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr690 695 700Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro705 710 715 720Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val725 730 735Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala740 745 750His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys755 760 765Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln770 775 780Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala785 790 795 800Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met805 810 815Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly820 825 830Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg835 840 845Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala850 855 860
Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala865 870 875 880Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu885 890 895Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His900 905 910Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly915 920 925Asn Ala Thr Thr930210122211960212PRT213黑猩猩腺病毒-ChAd 3六鄰體400122Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr65 70 75 80Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135 140Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu145 150 155 160Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu165 170 175Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala180 185 190Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro195 200 205Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val210 215 220Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr225 230 235 240Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu245 250 255Thr Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe260 265 270Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Ala Asn Asn Ile Gln Pro275 280 285Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr290 295 300His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile Met305 310 315 320Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg325 330 335Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly340 345 350Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln355 360 365Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly370 375 380Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr385 390 395 400Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr420 425 430Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp435 440 445Thr Lys Asp Glu Thr Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn450 455 460Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe465 470 475 480Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn485 490 495Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met500 505 510Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu515 520 525Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn530 535 540His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn545 550 555 560Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala565 570 575Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn580 585 590Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp595 600 605Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr610 615 620Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala625 630 635 640Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser645 650 655Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro660 665 670Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp690 695 700Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe705 710 715 720Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser725 730 735Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu740 745 750Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn755 760 765Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile770 775 780Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr785 790 795 800Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln805 810 815Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn820 825 830Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln835 840 845Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val850 855 860Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg865 870 875 880Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu885 890 895Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr900 905 910Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe915 920 925Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile930 935 940Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 955 960
210123211937212PRT213黑猩猩腺病毒-ChAd 6六鄰體400123Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Ser Gln Trp Ile Thr Lys Asp Asn Gly Thr Asp Lys130 135 140Thr Tyr Ser Phe Gly Asn Ala Pro Val Arg Gly Leu Asp Ile Thr Glu145 150 155 160Glu Gly Leu Gln Ile Gly Pro Asp Glu Ser Gly Gly Glu Ser Lys Lys165 170 175Ile Phe Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Leu Gly Asp Glu180 185 190Glu Trp His Asp Thr Ile Gly Ala Glu Asp Lys Tyr Gly Gly Arg Ala195 200 205
Leu Lys Pro Ala Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys210 215 220Pro Thr Asn Ala Lys Gly Gly Gln Ala Lys Ser Arg Thr Lys Asp Asp225 230 235 240Gly Thr Thr Glu Pro Asp Ile Asp Met Ala Phe Phe Asp Asp Arg Ser245 250 255Gln Gln Ala Ser Phe Ser Pro Glu Leu Val Leu Tyr Thr Glu Asn Val260 265 270Asp Leu Asp Thr Pro Asp Thr His Ile Ile Tyr Lys Pro Gly Thr Asp275 280 285Glu Thr Ser Ser Ser Phe Asn Leu Gly Gln Gln Ser Met Pro Asn Arg290 295 300Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr305 310 315 320Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu325 330 335Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln340 345 350Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp355 360 365Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn370 375 380His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Gly385 390 395 400Val Gly Phe Thr Asp Thr Phe Gln Gly Ile Lys Val Lys Thr Thr Asn405 410 415Asn Gly Thr Ala Asn Ala Thr Glu Trp Glu Ser Asp Thr Ser Val Asn420 425 430Asn Ala Asn Glu Ile Ala Lys Gly Asn Pro Phe Ala Met Glu Ile Asn435 440 445Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu450 455 460Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro465 470 475 480
Ala Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro485 490 495Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp500 505 510Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu515 520 525Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His530 535 540Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu545 550 555 560Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met565 570 575Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser580 585 590Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala595 600 605His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn610 615 620Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro625 630 635 640Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn645 650 655Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu660 665 670Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly675 680 685Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys690 695 700Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp705 710 715 720Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly725 730 735Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu740 745 750
Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val755 760 765Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln770 775 780Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln785 790 795 800Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr805 810 815Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro820 825 830Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys835 840 845Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe850 855 860Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala865 870 875 880Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp885 890 895Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg900 905 910Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr915 920 925Pro Phe Ser Ala Gly Asn Ala Thr Thr930 935210124211956212PRT213黑猩猩腺病毒-C1六鄰體400124Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Ser Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Ser Gln Trp Leu Asp Lys Gly Val Thr Thr Thr Asp130 135 140Asn Asn Thr Glu Asn Gly Asp Glu Glu Asp Glu Val Ala Glu Glu Gly145 150 155 160Glu Glu Glu Lys Gln Ala Thr Tyr Thr Phe Gly Asn Ala Pro Val Lys165 170 175Ala Glu Ala Glu Ile Thr Lys Glu Gly Leu Pro Ile Gly Leu Glu Val180 185 190Pro Ser Glu Gly Asp Pro Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln195 200 205Pro Glu Pro Gln Val Gly Glu Glu Ser Trp Thr Asp Thr Asp Gly Thr210 215 220Asp Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro Glu Thr Lys Met Lys225 230 235 240Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val Lys Gly Gly Gln245 250 255Ala Lys Val Lys Lys Val Glu Glu Gly Lys Val Glu Tyr Asp Ile Asp260 265 270Met Asn Phe Phe Asp Leu Arg Ser Gln Lys Thr Gly Leu Lys Pro Lys275 280 285
Ile Val Met Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr His290 295 300Val Val Tyr Lys Pro Gly Ala Ser Asp Ala Ser Ser His Ala Asn Leu305 310 315 320Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp325 330 335Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val340 345 350Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp355 360 365Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp370 375 380Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp385 390 395 400Pro Asp Val Arg Val Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro405 410 415Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Pro Arg Thr Asp Ser Tyr420 425 430Lys Gly Ile Glu Thr Asn Gly Asp Glu Asn Thr Thr Trp Lys Asp Leu435 440 445Asp Pro Asn Gly Ile Ser Glu Leu Ala Lys Gly Asn Pro Phe Ala Met450 455 460Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn465 470 475 480Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Thr Asn Val485 490 495Thr Leu Pro Glu Asn Lys Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val500 505 510Val Pro Pro Ser Leu Val Asp Thr Tyr Val Asn Ile Gly Ala Arg Trp515 520 525Ser Leu Asp Ala Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn530 535 540Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val545 550 555 560
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Val Lys Asn Leu565 570 575Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp580 585 590Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp595 600 605Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe610 615 620Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn625 630 635 640Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met645 650 655Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro660 665 670Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys675 680 685Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val690 695 700Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His705 710 715 720Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro725 730 735Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr740 745 750Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp755 760 765Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly770 775 780Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg785 790 795 800Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys805 810 815Asp Tyr Lys Ala Val Ala Val Pro Tyr Gln His Asn Asn Ser Gly Phe820 825 830
Val Gly Tyr Met Ala Pro Thr Met Arg Gln Gly Gln Ala Tyr Pro Ala835 840 845Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr850 855 860Gln Lys Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser865 870 875 880Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu885 890 895Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp900 905 910Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp915 920 925Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr930 935 940Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr945 950 955210125211933212PRT213黑猩猩腺病毒-CV68六鄰體400 125Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala1 5 10 15Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala20 25 30Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro35 40 45Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu50 55 60Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met85 90 95Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser100 105 110Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly115 120 125Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Asp Gly Glu Thr Ala130 135 140Thr Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Asn145 150 155 160Ile Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro165 170 175Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala180 185 190Glu Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala195 200 205Leu Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys210 215 220Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Gly Thr Gly225 230 235 240Thr Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser245 250 255Ala Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn260 265 270Val Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr275 280 285Asp Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ala Met Pro Asn290 295 300Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr305 310 315 320Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln325 330 335Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr340 345 350
Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met355 360 365Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu370 375 380Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp385 390 395 400Ala Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Thr405 410 415Asp Gln Thr Thr Trp Thr Lys Asp Asp Ser Val Asn Asp Ala Asn Glu420 425 430Ile Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn435 440 445Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp450 455 460Set Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu Pro Thr Asn Thr Asn465 470 475 480Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp485 490 495Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn500 505 510Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser515 520 525Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro530 535 540Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr545 550 555 560Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser565 570 575Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr580 585 590Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala595 600 605Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe610 615 620
Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn625 630 635 640Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe645 650 655Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu660 665 670Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr675 680 685Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile690 695 700Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr705 710 715 720Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn725 730 735Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu740 745 750Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr755 760 765Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg770 775 780Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu785 790 795 800Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr805 810 815Met Arg Gln Gly Gln Pro Tyr Pro Ala Xaa Tyr Pro Tyr Pro Leu Ile820 825 830Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu Cys Asp835 840 845Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly850 855 860Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His865 870 875 880Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu885 890 895
Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro900 905 910His Arg Gly Val Ile Glu Ala Val Tyr Xaa Arg Thr Pro Phe Ser Ala915 920 925Gly Asn Ala Thr Thr930
權利要求
1. 一種分離的黑猩猩核酸序列，選自由以下構成的組a)SEQ ID NO1b)SEQ ID NO2；和c)與(a)或(b)的序列互補的核酸序列。
2.分離的重組黑猩猩血清型，包含選自下組的六鄰體和纖維核酸序列的任何組合a)選自由SEQ ID NO16-25、41、43、97、99、101、103、105、107、109、111、113、115和117構成的組的六鄰體基因序列；和b)選自由SEQ ID NO6-15、42、44、58、60、62、64、66、68、70、72、74、76和78構成的組的纖維基因序列。
3.一種分離的重組黑猩猩血清型，包含來源於腺病毒的六鄰體和纖維核酸序列的任何組合，所述腺病毒選自由ECACC登記號03121201(ChAd4)、03121202(ChAd5)、03121203(ChAd7)、03121204(ChAd9)、03121205(ChAd10)、03121206(ChAd11)、03121207(ChAd16)、03121208(ChAd17)、03121209(ChAd19)和03121210(ChAd20)構成的分離物的組。
4.一種複製缺陷性黑猩猩腺病毒(ChAd)載體，包含來源於腺病毒的核苷酸序列，所述腺病毒選自由ECACC登記號03121201(ChAd4)、03121202(ChAd5)、03121203(ChAd7)、03121204(ChAd9)、03121205(ChAd10)、03121206(ChAd11)、03121207(ChAd16)、03121208(ChAd17)、03121209(ChAd19)和03121210(ChAd20)構成的分離物的組，和與調節序列可操作連接的編碼至少一個免疫原的轉基因，所述調節序列指導所述轉基因在哺乳動物細胞中的表達，其中所述載體缺少包含選自由腺病毒E1、E2、E3和E4構成的組的至少一個腺病毒基因的核苷酸。
5. 種複製缺陷性黑猩猩腺病毒(ChAd)載體，包含在SEQ IDNO1或SEQ ID NO2中列出的核苷酸序列，和與調節序列可操作連接的編碼至少一個免疫原的轉基因，所述調節序列指導所述轉基因在哺乳動物細胞中的表達，其中所述載體缺少SEQ ID NO1或SEQ IDNO2的核苷酸序列，所述核苷酸序列包含選自由腺病毒E1、E2、E3和E4構成的組的至少一個基因。
6.一種複製缺陷性ChAd載體，其包含在SEQ ID NO1的bp460到bp3542、或SEQ ID NO2的bp 457到bp3425的區域中、在E1核苷酸序列中的刪除/破壞。
7. 根據權利要求6的ChAd載體，其中所述載體包含選自以下構成的組的轉基因HIV、HBV、HCV、HPV、HSV1、HSV2、SARSCoV、Plasmodium malariae、伊波拉病毒、西尼羅河病毒、登革熱病毒、流感A、流感B和Mycobacterium tubercolosis。
8. 根據權利要求6的ChAd載體，其中所述載體包含在SEQ IDNO1的bp460到bp3542、或SEQ ID NO2的bp457到bp3425的區域中、在E1核苷酸序列中的刪除/破壞，和進一步的其中所述載體包含編碼至少一個腫瘤相關抗原(TAA)的轉基因。
9. 根據權利要求8的ChAd載體，其中所述至少一個TAA選自由以下構成的組HER2 NEU、CEA、EPCAM、PSA、PSMA、端粒酶、GP100、MELAN-A/MART-1、MUC-1、NY-ESO-1、存活蛋白、溶基質蛋白酶3、酪氨酸酶、MAGE3、CML68、CML66、OY-TES-1、SSX-2、SART-1、SART-2、SART-3、NY-CO-58、NY-BR-62、HKLP2、5T4和VEGFR2。
10.一種宿主細胞，包含根據權利要求1或權利要求2的核酸分子，其中所述宿主細胞表達選自由E1a、E1b、E2a、E2b、E4orfs 1、2、3、4、5、6、6/7、pIX、IVa2、區域L1、L2、L3、L4、L5構成的組的一種或多種腺病毒區域。
11.生產複製缺陷性黑猩猩腺病毒載體的方法，包括將根據權利要求5的腺病毒載體導入表達腺病毒E-1的人類細胞，並收穫產生的腺病毒。
12.根據權利要求11的方法，其中所述人類細胞是293細胞或PER.C6TM細胞。
13.一種疫苗組合物，包含根據權利要求4-6的任何一個的複製缺陷性ChAd載體。
14.表達腺病毒E1的人類細胞，包含SEQ ID NO1中所列的核苷酸序列。
15.表達腺病毒E1的人類細胞，包含SEQ ID NO2中所列的核苷酸序列。
16.在哺乳動物中強化抗原特異性免疫反應的方法，包括向所述哺乳動物施用足夠量的重組ChAd載體，其包含含有其E1基因的至少功能性刪除的黑猩猩腺病毒基因組、編碼目標抗原的核苷酸序列和能指導編碼所述目標抗原的所述核苷酸序列的表達的啟動子序列，其中施用所述chAd載體引發強化的反應。
17.權利要求16的方法，其中所述ChAd載體包含其E1基因的完全刪除，和進一步的其中所述載體任選的包含其E3基因的刪除。
18.權利要求16的方法，其中所述強化的免疫反應特異於抗原，所述抗原來源於選自以下構成的組的傳染原HIV、HBV、HCV、HPV、HSV1、HSV2、SARS CoV、Plasmodium malariae、伊波拉病毒、西尼羅河病毒、登革熱病毒、流感A、流感B和Mycobacteriumtubercolosis。
19.權利要求16的方法，其中所述免疫反應是特異於TAA的強化的免疫反應。
20.權利要求19的方法，其中所述強化的免疫反應包括產生抗原特異性CD8+T細胞。
21.權利要求16的方法，其中所述強化的免疫反應包括產生抗原特異性CD8+T細胞。
22.在幼稚哺乳動物中引發免疫反應的方法，包括向所述哺乳動物施用足夠量的ChAd載體，其包含含有其E1基因的至少功能性刪除的黑猩猩腺病毒基因組、編碼目標抗原的核苷酸和能指導編碼所述目標抗原的所述核苷酸序列的表達的啟動子序列，其中施用所述chAd載體引發初級免疫反應。
23.權利要求22的方法，其中所述初級免疫反應特異於來源於傳染原的抗原，所述傳染原例如，但不限於HIV、HCV、HPV、HSV1、HSV2、SARS CoV、Plasmodium malariae、伊波拉病毒、西尼羅河病毒、登革熱病毒、流感A、流感B和Mycobacterium tubercolosis。
24.權利要求16的方法，其中所述免疫反應是特異於TAA的初級免疫反應，所述哺乳動物針對所述TAA是耐受性的。
25.根據權利要求16的方法，其中所述重組腺病毒包含編碼由胺基酸序列組成的六鄰體肽的核苷酸序列，所述胺基酸序列選自由SEQID NO87-96、98、100、102、104、106、108、110、112、114、116、118、122和123構成的組。
26.根據權利要求16的任何一個的方法，其中所述重組腺病毒包含編碼由胺基酸序列組成的纖維蛋白的核苷酸序列，所述胺基酸序列選自由SEQ ID NO48-57、59、61、63、65、67、69、71、73、75、77、79、83和84構成的組。
27.誘導針對來源於傳染原的抗原的免疫反應的方法，所述傳染原選自以下構成的組HIV、HCV、HPV、HSV1、HSV2、SARS、Plasmodium malariae、伊波拉病毒、西尼羅河病毒、登革熱病毒、流感A、流感B和Mycobacterium tubercolosis，包括步驟(a)通過施用第一疫苗組合物激發宿主以響應傳染原-抗原，所述第一疫苗組合物包含編碼傳染原-抗原的核苷酸序列，針對所述傳染原-抗原的抗原特異性免疫反應是期望的；和(b)通過施用第二疫苗組合物強化步驟(a)的免疫反應，所述第二疫苗組合物包含含有其E1基因的至少功能性刪除的重組ChAd載體，和在所述E1基因刪除的位點中，包含一序列，所述序列包含能指導DNA的表達的啟動子，所述DNA編碼與激發步驟中遞送的相同的傳染原-抗原；其中所述強化組合物的施用引發具有賦予保護性免疫的效果的免疫反應。
28.根據權利要求27的方法，其中所述第一疫苗組合物包含質粒DNA，其與電刺激一同肌肉內地施用。
29.根據權利要求27的方法，其中所述第二疫苗組合物包含ChAd載體，所述ChAd載體包含編碼來源於傳染原的抗原的DNA，所述傳染原選自以下構成的組HIV、HCV、HPV、HSV1、HSV2、SARS、瘧疾、伊波拉病毒、西尼羅河病毒、登革熱病毒、流感A、流感B和Mycobacterium tubercolosis。
30.權利要求27的方法，其中所述免疫反應包括產生抗原特異性CD8+T細胞。
31.權利要求30的方法，其中所述ChAd載體來源於選自以下構成的組的腺病毒ChAd3、ChAd6、ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82。
32.權利要求30的方法，其中所述ChAd載體包含編碼由胺基酸序列組成的六鄰體肽的核苷酸序列，所述胺基酸序列選自由SEQ IDNO87-96、98、100、102、104、106、108、110、112、114、116、118、122和123構成的組。
33.權利要求30的方法，其中所述ChAd載體包含編碼由胺基酸序列組成的纖維蛋白的核苷酸序列，所述胺基酸序列選自由SEQ IDNO48-57、59、61、63、65、67、69、71、73、75、77、79、83和84構成的組。
34.權利要求30的方法，其中所述第一和第二疫苗組合物是以不同的血清型為特徵的ChAd載體。
35.破壞宿主對自體抗原的耐受性的方法，包括(a)通過施用第一疫苗組合物激發宿主以響應自體抗原，所述第一疫苗組合物包含編碼自體抗原的核苷酸序列，針對所述自體抗原的抗原特異性免疫反應是期望的，從而引發激發的反應；和(b)通過施用第二疫苗組合物強化步驟(a)的激發的免疫反應，所述第二疫苗組合物包含含有其E1基因的至少功能性刪除的重組ChAd載體，和在所述E1基因刪除的位點中，包含一序列，所述序列包含能指導DNA的表達的啟動子，所述DNA編碼與激發步驟中遞送的相同的自體抗原，其中所述強化組合物的施用引發具有破壞宿主對所述自體抗原的耐受性的效果的免疫反應。
36.根據權利要求35的方法，其中所述第一疫苗組合物包含質粒DNA，其與電刺激一同肌肉內地施用。
37.權利要求35的方法，其中所述第二疫苗組合物包含ChAd載體，所述ChAd載體包含編碼自體抗原的DNA，所述自體抗原選自以下構成的組HER2 NEU、CEA、HEPCAM、PSA、PSMA、端粒酶、GP100、MELAN-A/MART-1、MUC-1、NY-ESO-1、存活蛋白、溶基質蛋白酶3、酪氨酸酶、MAGE3、CML68、CML66、OY-TES-1、SSX-2、SART-1、SART-2、SART-3、NY-CO-58、NY-BR-62、HKLP2、5T4和VEGFR2。
38.權利要求35的方法，其中所述免疫反應包括產生抗原特異性CD8+T細胞。
39.權利要求35的方法，其中所述ChAd載體來源於選自以下構成的組的腺病毒ChAd3、ChAd6、ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82。
40.權利要求35的方法，其中所述ChAd載體包含編碼由胺基酸序列組成的六鄰體肽的核苷酸序列，所述胺基酸序列選自由SEQ IDNO87-96、98、100、102、104、106、108、110、112、114、116、118、122和123構成的組。
41.權利要求35的方法，其中所述ChAd載體包含編碼由胺基酸序列組成的纖維肽的核苷酸序列，所述胺基酸序列選自由SEQ IDNO48-57、59、61、63、65、67、69、71、73、75、77、79、83和84構成的組。
42.權利要求35的方法，其中所述第一和第二疫苗組合物疫苗組合物都是以不同的血清型為特徵的ChAd載體。
全文摘要
本發明提供來源於黑猩猩腺病毒的重組複製缺陷性腺病毒載體和用於在人類E1表達細胞系中產生重組腺病毒的方法。本發明還提供了適用於遞送和表達編碼免疫原的轉基因的組合物和方法，針對所述免疫原的強化的免疫反應是期望的。本發明進一步提供了產生適合在人類中使用的臨床級載體成品的方法。在特定的實施方式中，本發明考慮在疫苗和藥物組合物中使用包含編碼腫瘤相關抗原的轉基因的載體用於癌症的預防和治療。
文檔編號A61K48/00GK101014613SQ200580003043
公開日2007年8月8日 申請日期2005年1月18日 優先權日2004年1月23日
發明者A·奇裡洛, S·科洛卡, B·B·埃爾科勒, A·梅奧拉, A·尼科西亞, E·斯波雷諾 申請人:P·安傑萊蒂分子生物學研究所