CN107723298A - 黑猩猩腺病毒疫苗载运体 - Google Patents

黑猩猩腺病毒疫苗载运体 Download PDF

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CN107723298A
CN107723298A CN201710767616.5A CN201710767616A CN107723298A CN 107723298 A CN107723298 A CN 107723298A CN 201710767616 A CN201710767616 A CN 201710767616A CN 107723298 A CN107723298 A CN 107723298A
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adenovirus
cell
carrier
sequence
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A.奇里洛
S.科洛卡
B.B.埃尔科勒
A.梅奥拉
A.尼科西亚
E.斯波雷诺
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Istituto di Ricerche di Biologia Molecolare P Angeletti SpA
MSD Italia SRL
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Abstract

本发明涉及黑猩猩腺病毒疫苗载运体。本发明提供来源于黑猩猩腺病毒的重组复制缺陷性腺病毒载体和用于在人类E1表达细胞系中产生重组腺病毒的方法。本发明还提供了适用于递送和表达编码免疫原的转基因的组合物和方法,针对所述免疫原的强化的免疫反应是期望的。本发明进一步提供了产生适合在人类中使用的临床级载体成品的方法。在特定的实施方式中,本发明考虑在疫苗和药物组合物中使用包含编码肿瘤相关抗原的转基因的载体用于癌症的预防和治疗。

Description

黑猩猩腺病毒疫苗载运体
本申请是申请日为2005年1月18目的中国专利申请201210056795.9“黑猩猩腺病毒疫苗载运体”的分案申请。
相关申请的交叉引用
本申请要求于2004年1月23日提交的美国临时申请No.60/538,799的权益,通过引用将它合并在此。
技术领域
本发明涉及重组载体领域,更具体地涉及重组复制缺陷性黑猩猩腺病毒载体的产生和用途,来在哺乳动物宿主中引发免疫反应。
背景技术
腺病毒(Ads)包含在两栖动物、禽类和哺乳动物中发现的、具有无包被的二十面体衣壳结构的双链DNA病毒的大家族(Straus,Adenovirus infections in humans.In TheAdenoviruses.451-498,1984;Hierholzer et al.,J.Infect.Dis.,158:804-813,1988;Schnurr and Dondero,Intervirology.,36:79-83,1993;Jong et al.,J ClinMicrobiol.,37:3940-3945:1999)。与逆转录病毒相比,腺病毒可以转导几个哺乳动物物种的许多细胞类型,包括分裂和非分裂细胞,而不整合到宿主细胞的基因组中。
一般而言,腺病毒DNA一般是非常稳定的并保持游离(例如,染色体外),除非发生了转化或肿瘤发生。此外,在容易进行临床级组合物的制药规模生产的良好定义的生产系统中,腺病毒载体可以繁殖到高产量。这些特征和它们被良好表征的分子遗传学,使得重组腺病毒载体成为用作疫苗载运体(carrier)的好的候选者。一般地,重组腺病毒载体的生产依靠使用能够补足腺病毒基因产物的功能的包装细胞系,所述功能已经被删除或被工程化为无功能的。
目前,两种良好表征的人类C亚群腺病毒血清型(即,hAd2和hAd5)被广泛地用作大多数用于基因治疗的腺病毒载体的病毒主干的来源。也已经测试了复制缺陷性人类腺病毒载体作为用于递送各种免疫原的疫苗载体,所述免疫原来源于各种传染原(例如,病毒、寄生虫或细菌性病原体)和肿瘤细胞,包括肿瘤相关抗原(TAA)。在实验动物(例如,啮齿动物、犬和非人灵长类)中进行的研究表明,携带转基因的重组复制缺陷性人类腺病毒载体引发了针对转基因产物的体液和细胞介导的免疫反应,所述转基因编码来源于人类乳头状瘤病毒(HPV-16)的E6和E7癌蛋白(He,Z et al.,(2001)Virology,270:3583-3590)、狂犬病病毒糖蛋白(Xiang,Z.et al(1996)Virolgy,219:220-227)、Plasmodium falciparum的环子孢子蛋白Rodriguez E.et al.(1997)J.Immunol.158:1268-1274)以及其他异源抗原的免疫原。一般而言,研究人员已经报道了,通过使用利用预计可引发免疫反应的高剂量重组腺病毒载体的免疫方案;或通过使用采用腺病毒载体的连续施用的免疫方案,所述腺病毒载体来源于不同血清型但携带相同的转基因产物用作强化免疫,在非人类实验系统中成功地使用人类腺病毒载体作为疫苗载运体(Mastrangeli,et al.,Human Gene Therapy,7:79-87(1996)。
然而,预计的是,来源于遍在的人类血清型,例如2和5型的疫苗载运体将在人类群体中遇到先存的(pre-existing)体液和细胞免疫。因而,尽管已经在采用啮齿动物、犬和非人灵长类宿主的实验系统中成功地使用复制缺陷性重组人类腺病毒作为疫苗载运体,预计人类的先天和适应性免疫会显著地限制这些血清型作为疫苗载运体的实用性。这种预期是基于这一事实,包括2型和5型的C亚群腺病毒感染在人类群体中是地方性的。结果,作为自然感染的结果,大多数人类在生命的头五年内血清转变。因而,来源于在人类中天然感染并复制的病毒的载体,可能不是用作疫苗载运体的最优候选者。
与使用人类腺病毒衍生载体相关的另一个问题是,用于繁殖重组病毒的生产方法产生被有复制能力的腺病毒(RCA)污染的载体成品的风险。这是起因于,来自重组载体和存在于E1补足辅助细胞系,例如人类293(Graham,F.L.et al,(1977)J.Gen.Virol.36:59-72.)细胞中的腺病毒基因的重叠序列之间的同源重组。在为用于临床试验制备的载体成品中RCA的存在构成了安全风险,因为它可能促进复制缺陷性病毒的流动和传播。缺陷病毒的传播可能加重宿主免疫应答,并引起其他有害的免疫病理后果。(Fallux,F.J.,etal.Human Gene Therapy 9:1909-1917(1998)。因此,食品和药品管理局(FDA)和其他管理机构已经颁布了指导原则,其建立了对可能存在于用于临床用途的载体制品中的RCA水平的限制。加以RCA限制的意图是确保患者有限地暴露于用于临床试验的组合物中的复制性腺病毒。
因而,存在着开发适用于哺乳动物宿主的腺病毒疫苗载运体的持续的需求,其是:易于操作、可经受制药规模的生产和长期储存、在人类补足细胞系中能以高水平复制、高度的免疫原性、没有与人类腺病毒的常见血清型交叉反应的中和B细胞表位、符合管理机构颁布的安全RCA标准、并且其符合在适合人类使用的激发/强化(prime/boost)方案中使用。
发明内容
本发明涉及来源于黑猩猩腺病毒的重组复制缺陷性腺病毒载体和用于在人类E1表达细胞系中产生黑猩猩腺病毒载体的方法。本发明还提供了产生适用于人类的临床级载体成品的方法,和使用所公开的载体作为疫苗载运体来引发保护性和/或治疗性免疫反应的方法。本发明进一步提供了使用本发明的重组腺病毒来制备疫苗组合物的方法,所述疫苗组合物被设计以递送编码免疫原的转基因和指导编码免疫原的转基因的表达。在一个实施方式中,本发明考虑使用所公开载体作为疫苗载运体用于疫苗的施用,所述疫苗包含编码来源于传染原的免疫原的转基因。在第二种实施方式中,本发明考虑使用所公开的载体来制备和施用癌症疫苗。在特定的实施方式中,本发明考虑制备和施用包含编码TAA的转基因的癌症疫苗。
在一个方面,本发明公开了五种黑猩猩腺病毒(ChAds)的完整基因组序列,在此称为ChAd3(SEQ ID NO:1)(附图5A-5K)、ChAd6(SEQ ID NO:2)(附图6A-6K)、CV32(SEQ ID NO:3)(附图7A-7K)、CV33(SEQ ID NO:4)(附图8A-8K)和CV23(SEQ ID NO:5)(附图9A-9J)。
ChAd3和ChAd6是根据在此公开的方法分离的新的腺病毒。ChAd3和ChAd6的基因组长度分别是37741和36648个碱基对。ChAd3六邻体基因(SEQ ID NO:41)包含SEQ ID NO:1的核苷酸(nt)19086-21965(不包括终止密码子),ChAd3纤维基因(SEQ ID NO:42)包含SEQ IDNO:1的nt 32805-34487(不包括终止密码子)。ChAd6六邻体(hexon)基因包含SEQ ID NO:2的nt18266-21124(SEQ ID NO:43)(不包括终止密码子),它的纤维基因(SEQ ID NO:44)包含SEQ ID NO:2的nt 32218-33552(不包括终止密码子)。根据从全长六邻体肽的多重序列比对得出的序列同源性,ChAd3被分类入人类C亚群,ChAd6被分类入人类E亚群。
CV32、CV33和CV23腺病毒的基因组的长度分别是36,606、36,535和32,020个碱基对。CV32(Pan 6)(ATCC N.VR-592)、CV33(Pan 7)(ATCC N.VR-593)和CV23(Pan 5)(Esoterix Inc.,)全都被确定为与人类Ad4(hAd4)(E亚群)相关(Wigand,R etal.Intervirology 1989,30:1-9)。然而,根据六邻体序列比对,随后将CV32表征为与类似于hAd4相比更接近地类似于人类D亚群成员。
在第二个方面,本发明提供了根据在此公开的方法分离的21种其他黑猩猩腺病毒(ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82)的纤维基因和六邻体基因的核苷酸序列。
ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19的纤维基因核苷酸序列分别在附图10-19中列出,在此称为SEQ ID NO:6-15:(SEQ ID NO:6,ChAd20);(SEQ ID NO:7,ChAd4);(SEQ ID NO:8,ChAd5);(SEQ ID NO:9,ChAd7);(SEQ IDNO:10,ChAd9);(SEQ ID NO:11,ChAd10);(SEQ ID NO:12,ChAd11);(SEQ ID NO:13,ChAd16)(SEQ ID NO:14,ChAd17)和(SEQ ID NO:15,ChAd19)
ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的纤维基因核苷酸序列在此称为:(SEQ ID NO:58,ChAd8)、(SEQ ID NO:60,ChAd22)、(SEQ ID NO:62,ChAd24)、(SEQ ID NO:64,ChAd26)、(SEQ ID NO:66,ChAd30)、(SEQ ID NO:68,ChAd31)、(SEQ ID NO:70,ChAd37)、(SEQ ID NO:72,ChAd38)、(SEQ BD NO:74,ChAd44)、(SEQ ID NO:76,ChAd63)和(SEQ ID NO:78,ChAd82),并在序列表中列出。
ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19的六邻体基因核苷酸序列分别在附图21-30中列出,在此称为SEQ ID NO:16-25:(SEQ ID NO:16,ChAd20);(SEQ ID NO:17,ChAd4);(SEQ ID NO:18,ChAd5);(SEQ ID NO:19,ChAd7);(SEQ ID NO:20,ChAd9);(SEQ ID NO:21,ChAd10);(SEQ ID NO:22,ChAd11);(SEQ ID NO:23,ChAd16);(SEQ ID NO:24,ChAd17)和(SEQ ID NO:25,ChAd19)。
ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的六邻体基因核苷酸序列在此称为:(SEQ ID NO:97,ChAd8)、(SEQ ID NO:99,ChAd22)、(SEQ ID NO:101,ChAd24)、(SEQ ID NO:103,ChAd26)、(SEQ ID NO:105,ChAd30)、(SEQ ID NO:107,ChAd31)、(SEQ ID NO:109,ChAd37)、(SEQ ID NO:111,ChAd38)、(SEQ IDNO:113,ChAd44)、(SEQ ID NO:115,ChAd63)和(SEQ ID NO:117,ChAd82),并在序列表中列出。
在第三个方面,本发明提供了根据在此公开的方法分离的21种其他黑猩猩腺病毒(ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82)的纤维蛋白和六邻体蛋白的氨基酸序列。
在此公开和要求权利的纤维蛋白称为:(SEQ ID NO:83,ChAd3)、(SEQ ID NO:84,ChAd6)、(SEQ ID NO:48,ChAd20)、(SEQ ID NO:49,ChAd4)、(SEQ ID NO:50,ChAd5)、(SEQID NO:51,ChAd7)、(SEQ ID NO:52,ChAd9)、(SEQ ID NO:53,ChAd10)、(SEQ ID NO:54,ChAd11)、(SEQ ID NO:55,ChAd16)、(SEQ ID NO:56,ChAd17)、(SEQ ID NO:57,ChAd19)、(SEQ ID NO:59,ChAd8)、(SEQ ID NO:61,ChAd22)、(SEQ ID NO:63,ChAd24)、(SEQ ID NO:65,ChAd26)、(SEQ ID NO:67,ChAd30)、(SEQ ID NO:69,ChAd31)、(SEQID NO:71,ChAd37)、(SEQ ID NO:73,ChAd38)、(SEQ ID NO:75,ChAd44)、(SEQ ID NO:77,ChAd63)和(SEQ IDNO:79,ChAd82)。附图20A一20G提供了比较在此公开和要求权利的纤维蛋白的氨基酸序列与以下纤维蛋白的氨基酸序列的比对:C1(SEQ ID NO:85)、CV68(SEQ ID NO:86)、Pan5(作为选择称为CV23)(SEQ ID NO:80)、Pan6(作为选择称为CV32)(SEQ ID NO:81)和Pan7(作为选择称为CV33)(SEQ ID NO:82)。
在此公开和要求权利的六邻体蛋白称为:(SEQ ID NO:122,ChAd3)、(SEQ ID NO:123,ChAd6)、(SEQ ID NO:87,ChAd20)、(SEQ ID NO:88,ChAd4)、(SEQ ID NO:89,ChAd5)、(SEQ ID NO:90,ChAd7)、(SEQ ID NO:91,ChAd9)、(SEQ ID NO:92,ChAd10)、(SEQ ID NO:93,ChAd11)、(SEQ ID NO:94,ChAd16)、(SEQ ID NO:95,ChAd17)、(SEQ ID NO:96,ChAd19)、(SEQ ID NO:98,ChAd8)、(SEQ ID NO:100,ChAd22)、(SEQ ID NO:102,ChAd24)、(SEQ IDNO:104,ChAd26)、(SEQ ID NO:106,ChAd30)、(SEQ ID NO:108,ChAd31)、(SEQ ID NO:110,ChAd37)、(SEQ ID NO:112,ChAd38)、(SEQ ID NO:114,ChAd44)、(SEQ ID NO:116,ChAd63)和(SEQ ID NO:118,ChAd82)。附图31A-31J提供了在此公开和要求权利的六邻体蛋白的氨基酸序列与以下六邻体蛋白的氨基酸序列的比较:C1(SEQ ID NO:124)、CV68(SEQ ID NO:125)、Pan5(做为选择称为CV23)(SEQ ID NO:119)、Pan6(做为选择称为CV32)(SEQ ID NO:120)和Pan7(做为选择称为CV33)(SEQ ID NO:121)。六邻体蛋白的多重序列比对容许技术人员进行与人类腺病毒血清型的建议分类一致的系统发生分析(Rux,J.J.,et al(2003)J.Virol.77:9553-9566)。
在可选择的方面,本发明进一步提供了21种其他的黑猩猩腺病毒分离物。将包含ChAd20、ChAd4、ChAd5、ChAd7、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的样品根据布达佩斯条约保藏在欧洲动物细胞保藏中心(ECACC,Porton Down,Salisbury,Wiltshire,SP4OJG,英国)。其保藏日、分类命名和保藏号如下表所示:
保藏日期 保藏编号 分类命名
2003年12月12日 03121201 CHIMPANZEE ADENOVIRUS TYPE 4
2003年12月12日 03121202 CHIMPANZEE ADENOVIRUS TYPE5
2003年12月12日 03121203 CHIMPANZEE ADENOVIRUS TYPE7
2003年12月12日 03121204 CHIMPANZEE ADENOVIRUS TYPE 9
2003年12月12日 03121205 CHIMPANZEE ADENOVIRUS TYPE 10
2003年12月12日 03121206 CHIMPANZEE ADENOVIRUS TYPE 11
2003年12月12日 03121207 CHIMPANZEE ADENOVIRUS TYPE 16
2003年12月12日 03121208 CHIMPANZEE ADENOVIRUS TYPE 17
2003年12月12日 03121209 CHIMPANZEE ADENOVIRUS TYPE 19
2003年12月12日 03121210 CHIMPANZEE ADENOVIRUS TYPE 20
2005年1月12日 05011201 ChAd8
2005年1月12日 05011202 ChAd22
2005年1月12日 05011203 ChAd24
2005年1月12日 05011204 ChAd26
2005年1月12日 05011205 ChAd30
2005年1月12日 05011206 ChAd31
2005年1月12日 05011207 ChAd37
2005年1月12日 05011208 ChAd38
2005年1月12日 05011209 ChAd44
2005年1月12日 05011210 ChAd63
2005年1月12日 05011211 ChAd82
这些保藏物将根据国际承认用于专利程序的微生物保藏布达佩斯条约的条款进行维持。这些保藏仅为了方便本领域技术人员而进行,而不是认可保藏是35U.S.C.§112所需的。在授予专利之时,除了37C.F.R.§1.808(b)规定的要求之外,对保藏的材料的公众可获得性的所有限制将被不可撤销地除去。
在其他方面,本发明还提供了复制缺陷性重组腺病毒载体,其能够感染哺乳动物细胞,优选的人类细胞,并指导编码的转基因产物的表达。如在此展示的,所公开的载体(vector)适合用做疫苗载运体(carrier)用于递送包含免疫原的转基因,针对所述免疫原的免疫反应是期望的。在特定实施方式中,本发明提供了能够在人类E1表达(即,包装)细胞系中高水平复制的重组复制缺陷性黑猩猩腺病毒载体。在一个实施方式中,本发明提供了能够在PER.C6TM细胞中复制的重组腺病毒。
一般而言,本发明包括的重组载体提供了能避开对腺病毒血清型的先存免疫的疫苗载运体,所述先存免疫是在人类群体中一般遇到的。更具体地说,本发明的重组载体包含载体主干序列,在此显示了其缺少与人类腺病毒衍生载体的常见血清型交叉反应的中和B表位。
本发明进一步提供了包括腺病毒部分和质粒部分的类群特异性的穿梭载体,其中所述腺病毒部分一般地包含:a)病毒左末端(ITR和包装信号)、pIX基因的部分和病毒基因组右末端;和b)基因表达盒。采用了在指定为相同血清型亚群(即,A、B、C、D或E亚群)的腺病毒之间观察到的核苷酸序列同一性设计类群特异性的穿梭载体,并可用于操作在此公开的核苷酸序列,和/或用于克隆属于相同亚群的其他黑猩猩腺病毒,产生含有删除了E1区域的黑猩猩腺病毒基因组的腺病毒前质粒(pre-plasmid)。
本发明的其他方面包括包含腺病毒疫苗载体和/或腺病毒前质粒载体的宿主细胞、生产所述载体的方法,包括将所述腺病毒疫苗载体导入表达腺病毒E1蛋白的宿主细胞中,并收获产生的腺病毒疫苗载体。在特定的实施方式中,本发明提供了生产复制缺陷性黑猩猩腺病毒载体的方法,包括将所公开的腺病毒载体之一导入表达腺病毒E-1的人类细胞,并收获产生的重组腺病毒。
本发明的另一个方面还提供了包含本发明的腺病毒载体的疫苗组合物。包含重组黑猩猩腺病毒载体的组合物可以单独施用或与其他基于病毒或非基于病毒的DNA/蛋白疫苗组合施用。它们也可以作为更广阔的治疗方式的部分来施用。这些组合物可以以预防性或治疗性的设置施用给哺乳动物宿主,优选人类宿主。如在此所示,单独地或以组合形式施用所公开的疫苗组合物,例如激发强化方式或不同血清型Ad载体的多次注射,引起哺乳动物中能够特异性识别由转基因编码的免疫原的免疫反应的诱导。
在此公开和要求权利的方法之一,包括向哺乳动物(是幼稚的(naive)或被激发以对目标抗原有免疫活性的)施用足够量的重组黑猩猩腺病毒载体,所述载体含有它的野生型E1基因的至少一个功能删除,带有包含启动子的序列,所述启动子能指导编码至少一个目标抗原的核苷酸序列的表达,其中施用所述重组抗体引发(或激发)抗原特异性免疫反应。
在一个实施方式中,本发明提供了设计以诱导针对传染原(例如,病毒或细菌性病原体或哺乳动物寄生虫)的免疫反应(预防性或治疗性的)的方法。在第二实施方式中,本发明提供了设计以在哺乳动物中诱导免疫反应的方法,所述免疫反应将破坏对自体抗原,例如TAA的耐受性。本发明的这个方面考虑使用所公开的载体作为疫苗载运体用于制备和施用癌症疫苗。
根据以下对发明的详细说明,本发明的其他实施方式和益处将显而易见。
附图说明
附图1是概括了用于构建ChAd6穿梭载体(pARS ChAd6-3)的克隆策略的示意图。
附图2是说明用于在E.coli菌株BJ5183中通过同源重组克隆ChAd6病毒基因组的克隆策略的示意图。
附图3是说明各种ChAd6穿梭质粒的元件的示意图,包括:pARS ChAd6-3 GAG;pARSChAd6-3 SEAP;pARS ChAd6-3 EGFP;和pARS ChAd6-3 NS MUT。
附图4是说明用于克隆ChAd6 ΔE1表达载体的同源重组方案的示意图。
附图5A-5K提供了ChAd3的基因组核苷酸序列(SEQ ID NO:1)。
附图6A-6K提供了ChAd6的基因组核苷酸序列(SEQ ID NO:2)。
附图7A-7K提供了CV32的基因组核苷酸序列(SEQ ID NO:3)。
附图8A-8K提供了CV33的基因组核苷酸序列(SEQ ID NO:4)。
附图9A-9J提供了CV23的基因组核苷酸序列(SEQ ID NO:5)。
附图10提供了ChAd20的纤维基因的核苷酸序列(SEQ ID NO:6)。
附图11提供了ChAd4的纤维基因的核苷酸序列(SEQ ID NO:7)。
附图12提供了ChAd5的纤维基因的核苷酸序列(SEQ ID NO:8)。
附图13提供了ChAd7的纤维基因的核苷酸序列(SEQ ID NO:9)。
附图14提供了ChAd9的纤维基因的核苷酸序列(SEQ ID NO:10)。
附图15提供了ChAd10的纤维基因的核苷酸序列(SEQ ID NO:11)。
附图16提供了ChAd11的纤维基因的核苷酸序列(SEQ ID NO:12)。
附图17提供了ChAd16的纤维基因的核苷酸序列(SEQ ID NO:13)。
附图18提供了ChAd17的纤维基因的核苷酸序列(SEQ ID NO:14)。
附图19提供了ChAd19的纤维基因的核苷酸序列(SEQ ID NO:15)。
附图20A-20G提供了以下的纤维蛋白的氨基酸序列:ChAd3、ChAd4、ChAd5、ChAd6、ChAd7、ChAd8、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd20、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82,与来自C1(SEQ ID NO:85)、CV68(SEQ ID NO:86)、PAN5(也称为CV23)(SEQ ID NO:80)、PAN6(也称为CV32)(SEQ IDNO:81)和Pan7(也称为CV33)(SEQ ID NO:82)的参考纤维蛋白序列的比较。
附图21提供了ChAd20的六邻体基因的核苷酸序列(SEQ ID NO:16)。
附图22提供了ChAd4的六邻体基因的核苷酸序列(SEQ ID NO:17)。
附图23提供了ChAd5的六邻体基因的核苷酸序列(SEQ ID NO:18)。
附图24提供了ChAd7的六邻体基因的核苷酸序列(SEQ ID NO:19)。
附图25提供了ChAd9的六邻体基因的核苷酸序列(SEQ ID NO:20)。
附图26提供了ChAd10的六邻体基因的核苷酸序列(SEQ ID NO:21)。
附图27提供了ChAd11的六邻体基因的核苷酸序列(SEQ ID NO:22)。
附图28提供了ChAd16的六邻体基因的核苷酸序列(SEQ ID NO:23)。
附图29提供了ChAd17的六邻体基因的核苷酸序列(SEQ ID NO:24)。
附图30提供了ChAd19的六邻体基因的核苷酸序列(SEQ ID NO:25)。
附图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的六邻体蛋白的氨基酸序列,与来自C1(SEQ ID NO:124)、CV68(SEQ ID NO:125)、PAN5(也称为CV23)(SEQ ID NO:119)、PAN6(也称为CV32)(SEQ IDNO:120)和Pan7(也称为CV33)(SEQ ID NO:121)的参考纤维蛋白序列的比较。
附图32提供在此公开的人工序列SEQ ID NO:26-40和SEQ ID NO:45和46,包括寡聚物和引物的列表。
附图33是属于不同血清型亚群(即,C、E和D亚群)的ChAd载体的免疫断点(break-point)的图示。通过在用表达gag的ChAd3、ChAd11、ChAd20、CV33、CV68、ChAd6、ChAd9、ChAd10、CV32、ChAd4、ChAd7和ChAd16载体免疫的小鼠中进行滴定实验,测定引发可测量免疫反应的最低剂量。
附图34提供了在恒河猴中引发的CEA特异性T细胞反应的图示,所述恒河猴次序地用人类腺病毒载体(MRKAd5 RhCEA)、12周间隔后用黑猩猩腺病毒载体(CV33 RhCEA)免疫。通过IFN-γ ELISPOT分析评估免疫反应,数据说明了在不存在(DMSO)和存在恒河猴CEA C和D肽库的情况下孵化之后每百万个外周血单核细胞(PBMC)中斑点形成细胞(SFC)的数目。
附图35提供了用PAUPSEARCH(Wisconsin Package Version 10.3,AceelrysInc.)进行全长六邻体肽序列的多重序列比对和用TREEVIEW进行可视化和操作得出的人类和黑猩猩腺病毒的系统树。
附图36是响应于向预先暴露于hAd5的小鼠施用ChAd3和hAd5 gag载体获得的免疫结果的图示。免疫后3周通过IFN-γ ELISPOT使用纯化的脾细胞评估细胞介导的免疫。
附图37是在用ChAd3hCEA和Ad5hCEA免疫的人类CEA转基因小鼠中引发的抗CEACMI的动力学的图示。通过用CEA肽库刺激的PBMC的ICS评估CMI。结果表示为IFNγ+CD8+/总PBMC的%。
附图38A-D是暴露于moi 50、250和1250的不同ChAd载体的不同人类初级细胞的感染效率的图示,所述ChAd载体表达EGFP并属于不同的亚群(B、C、D、E)。结果表示为荧光细胞/总细胞的%。
具体实施方式
如在整个说明书和附随的权利要求书中使用的,采用以下定义和缩写:
术语“盒”是指核酸分子,其包含至少一个要表达的核酸序列以及它的转录和翻译控制序列。改变所述盒,将使掺入了所述盒的载体指导不同序列或序列的组合的表达。在本发明的范围中,盒中存在的核酸序列通常编码免疫原。由于工程化的限制性位点存在于5′和3′末端,所述盒可以容易地插入、除去或用另一个盒替换。
术语“顺式作用元件”是指调节与它们连接的基因的核苷酸序列。存在于DNA中的顺式作用元件调节转录,转录成mRNA的那些能够调节RNA加工、转换(turnover)和蛋白质合成。
术语“载体”是指一些工具,通过它们能将DNA片段导入到宿主有机体或宿主组织中。存在着各种型式的载体,包括质粒、病毒(包括腺病毒)、噬菌体和粘粒。
术语“启动子”是指在DNA链上、RNA聚合酶能与之结合的识别位点。启动子与RNA聚合酶形成起始复合物来启动和驱动转录活性。通过活化序列例如增强子,或抑制序列例如沉默子,可以修饰所述复合物。
术语“药学有效量”是指重组腺病毒的数量,在特定施用途径中有效转导宿主细胞并提供足够的转基因表达水平以引发免疫反应。
术语“有复制能力的”重组腺病毒(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。野生型腺病毒是有复制能力的。
术语“复制缺陷性”重组AdV是指一种腺病毒,由于已经被工程化以具有病毒复制所必需的基因产物的至少一种功能删除或完全删除,而变得不能复制。本发明的重组黑猩猩腺病毒载体是复制缺陷性的。
术语“哺乳动物”是指任何哺乳动物,包括人类。
术语“序列同一性百分比”或“同一性”在核酸序列的上下文中是指当进行最大相关性比对时两个序列中的相同的残基。序列同一性比较的长度可以是在基因组的全长上(例如,约36kbp),基因的开放阅读框的全长上,蛋白、亚基或酶上[参见,例如,提供腺病毒编码区域的框],或至少约500到5000个核苷酸的片段上,是期望的。然而,在例如,至少约九个核苷酸、通常至少约20到24个核苷酸、至少约28到32个核苷酸、至少约36个或更多核苷酸的较小片段之间的同一性也是期望的。类似地,可以对氨基酸序列,在蛋白的全长上或其片段,容易地确定“序列同一性百分比”。适当地,片段长度至少约8个氨基酸,并可以达到约700个氨基酸。在此描述了适合的片段的实例。
在默认设置下使用在此定义的这种算法和计算机程序,容易地确定同一性。优选的,这种同一性是在蛋白、酶、亚基的全长上,或在长度至少约8个氨基酸的片段上进行的。然而,同一性可以基于更短的区域,在所述区域上适合于放入同一的基因产物的用途。
一般地,腺病毒构建体、基因构建体通过参考其中含有的基因来命名。例如,“pChAd3 ΔE1gag”是指包含删除了E1区域的ChAd3黑猩猩腺病毒基因组的质粒构建体。在这个质粒中,E1区域被免疫原表达盒替代,所述免疫原表达盒包含处在人类CMV启动子控制下之后是牛生长激素多聚腺苷酸信号的HIV gag基因。类似地,pCV33DE1-E3 NSmut是指在此公开的第二种质粒构建体,其包含删除了E1和E3区域的CV33黑猩猩腺病毒基因组,所述E1和E3区域被免疫原表达盒替代,所述免疫原表达盒包含处在人类CMV启动子控制下之后是牛生长激素多聚腺苷酸信号的HCV非结构基因。
缩写“Ag”是指抗原。
在整个说明书中和在附随的权利要求中使用的,单数形式“a”、“an”和“the”包括复数的引用,除非上下文中明显地另外指示了。
腺病毒(Ads)是已经在几种禽类和哺乳动物宿主中鉴定的无包被的二十面体病毒。人类Ads(hAd)属于Mastadenovirus属,包括所有已知的人类和动物(例如,牛、猪、犬、鼠、马、猿和绵羊)来源的许多Ads。根据许多生物学、化学、免疫学和结构标准,包括大鼠和恒河猴红血球的血细胞凝集性质、DNA同源性、限制性内切酶裂解模式、G+C含量百分比和致癌性,将人类腺病毒分成六个亚群(A-F)(Straus,1984,In The Adenoviruses,ed.H.Ginsberg,pps.451-498,New York:Plenus Press,and Horwitz,1990 In Virology,eds.B.N.Fields and D.M.Knipe,pps.1679-1721)。迄今为止,已经鉴定了51种不同的血清型,并根据它们的血细胞凝集性质和生物物理和生物化学标准分类成亚群。
腺病毒颗粒是二十面对称性的,取决于血清型,直径为60-90nm。二十面体衣壳由三种主要蛋白,六邻体(II)、五邻体基部(III)和隆突纤维(IV)以及许多微小蛋白(即,VI、VIII、IX、IIIa和IVa2)组成(W.C.Russel,J.Gen.Virol.,81:2573-2604(2000))。在人体中观察到的先存免疫性的一个方面是体液免疫,其可以引起特异于病毒蛋白的抗体的产生和存留。由腺病毒引发的体液反应主要地针对主要结构蛋白质:六邻体、五邻体和纤维。
公开的报道已经证实了,包含针对多种血清型的抗体的滴度是常见的(Dambrosio,E.(1982)J.Hyg.(London)89:209-219),先存滴度的重要部分具有中和活性。对腺病毒的中和免疫性是型特异性的(type-specific),特定血清型的腺病毒的感染仅赋予对该血清型的免疫性。一些报道已经表明,针对六邻体的抗体是最强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,对型特异性中和作用负责的表位位于七个高变区内,所述高变区是通过对从不同血清型得出的六邻体序列进行比对来鉴定的。(Crawford-Miksza,L andD.P.Schnurr.(1996)J.Virol. 70:1836-1844)。
已经通过不同的方法,包括免疫血清从处理的动物到幼稚动物的被动转移,证实了型特异性中和抗体的存在与用基于相同血清型的载体不能引发免疫反应之间的直接相关性。一般而言,对特定病毒血清型的先存体液免疫降低了载体施用的治疗效力。此外,施用基于特定病毒血清型的载体引发了针对该载体的、阻止相同血清型的重复施用的免疫反应。
在特定的实施方式中,本发明提供了一种绕过所述不利影响的方法,所述不利影响与对hAd的常见血清型的先存免疫性的后果有关。更具体地,本发明考虑使用以不在人类中传播的血清型为特征的黑猩猩腺病毒载体。因此,本发明提供了缺少与常见人类血清型的表位发生交叉反应的中和B细胞表位的腺病毒(Chad)载体作为疫苗载运体。
虽然已经报道了腺病毒特异性细胞介导的免疫性(CMI)可能是交叉反应性的,基于多种血清型的重复注射的疫苗接种研究表现了比基于单个载体的免疫程序更高的效率。这些实验进一步证明了疫苗目的的载体施用的主要局限是针对该载体的体液性先存免疫性。对使用人类腺病毒作为疫苗载运体有关的难题的可能解决方案包括,施用更高剂量的预测会遭遇先存免疫反应的腺病毒(例如,C亚群血清型),和使用基于稀有人类血清型的载体。然而,使用更高剂量的疫苗增加了疫苗的成本和不希望的副作用的风险,临床前测试的结果表明人类的另外的血清型比hAd5和hAd6有更低的免疫原性。
在避免针对载体的腺病毒主干元件的宿主体液和细胞免疫反应的问题和最小化使用可能被有复制能力的腺病毒(RCA)污染的人类腺病毒衍生载体成品的风险的尝试中,已经表征和开发了几种非人类腺病毒作为疫苗载运体(Soudois,C.et al(2000)J.Virology,74:10639-10649;Farina,S.F.et al(2001)J.Virology,75:11603-11613;Cohen,C.J.et al(2002)J.Gen.Virology,83:151-155.)。使用非人类腺病毒序列来绕过与先存免疫性有关的难题的前提基于这种观察结果,即针对常见人类腺病毒血清型的中和抗体不太可能交叉中和非人类病毒。然而,病毒和细胞因素的不相容性给大多数可选择的载体系统(牛、绵羊、犬)带来了实际的局限性,其特征在于必须在非人类细胞系中繁殖的缺点。
Wilson等已经公开了一报告,描述了基于黑猩猩腺病毒68型(CV68)C68的复制缺陷性载体的鉴定,所述腺病毒最初是从黑猩猩的肠系膜淋巴结分离的(Basnight,M.,et.al.(1971)Am.J.Epidemiol.94:166-171.),CV68被完全测序并发现在整体结构上类似于人类腺病毒(Farina,S.F.et al.,J.Virol.75(23):11603-11613(2001))。病毒的基因组长度是36,521碱基对,已经描述为最类似人类腺病毒的E亚群,与大多数已经测序的人类Ad4开放阅读框有90%的同一性。CV68ITRs的长度是130碱基对,存在所有主要的腺病毒早期和晚期基因。CV68的特征在于不在人类中传播(circulate)的血清型,其缺少与常见的人类血清型的表位交叉反应的中和B细胞表位。虽然黑猩猩腺病毒类似于人类腺病毒,但在人类中没有记录到针对黑猩猩血清型的交叉反应性中和免疫。(Farina,S.F.et al.J.Virol.(2001)75(23):11603-13)。
来源于CV68的重组载体被描述为足够类似于人类血清型以支持表达柯萨奇病毒(coxsackievirus)和腺病毒受体的细胞的转导(Cohen,C.et al.,J.Gen.Virol.83:151-155(2002)。重要地,CV68的特征是与人类腺病毒足够的相似性水平以支持它在携带来自人类腺病毒5型的E1的293细胞中复制(Farina,S.F.et al.,J.Virol.75(23):11603-11613(2001)。此外,根据人类血清型5E1的侧翼序列与CV68衍生载体序列的侧翼序列是非同源的这一观察结果,预计不会发生同源重组。因而,预计CV68衍生的疫苗成品(vaccine stocks)被RCA污染的可能性很低。
同一组研究者随后报道了,使用CV68衍生的腺病毒序列作为疫苗载运体用于在小鼠中诱导针对狂犬病病毒糖蛋白的抗体。通过用迷你基因(minigene)盒替换E1A和E1B基因产生了复制缺陷型的CV68。用含有E1删除、包含编码狂犬病病毒糖蛋白的转基因产物的腺病毒重组体(AdC68rab.gp)免疫的小鼠,发展出对狂犬病病毒的保护性免疫,并且对不然就是致死剂量的狂犬病病毒的攻击保持了抗性(Xiang,Z et al.,J.Virol.76(5):2667-2675(2002)。近来已经报道了表达密码子优化的、截短形式的HIV-1的gag的第二种CV68构建体在小鼠中诱导强有力的gag特异性CD8+T细胞反应。疫苗诱导反应显示了能提供对牛痘gag重组病毒攻击的保护(Fitzgerald,J.C.et al.,J.Immunol.170:1416-1422(2003)。对用人类腺病毒血清型5预先免疫的小鼠使用CV68gag或Ad5gag载体进行实验性疫苗接种展现出,与通过CV68疫苗引发的相比,通过Ad5引发的更显著的gag特异性T细胞的降低和对病毒攻击的保护。C68gag疫苗效力的降低是由于Ad5特异性CD8+T细胞的交叉反应性(同上)。
一同考虑这个数据表明,猿衍生的复制缺陷性腺病毒载体与基于常见的人类血清型的载体相比更适合用作人类疫苗载运体。如在此所示,用人类Ad5强烈免疫的小鼠(附图36)可以用ChAd3-gag腺病毒载体进行免疫的实验结果表明,先存的抗人类Ad5免疫性不会降低ChAd载体引发的gag特异性CMI反应。这些结果与人类Ad5交叉反应性B和T细胞表位不存在于ChAd3或ChAd6载体中的结论相一致。
一般而言,非常好地表征了腺病毒基因组,尽管存在几种不同的血清型,在类似地安置了特定功能的腺病毒基因组的整体结构上存在某些普遍的保守性。在美国专利No.6,083,716(黑猩猩腺病毒载体)和PCT公开的申请WO03/000851(快速筛选细菌转化体和新的猿腺病毒蛋白的方法)中提供了Wilson等公开的黑猩猩腺病毒C1和CV68的核苷酸序列,以及每个病毒的E1A、E1B、E2A、E2B、E3、E4、L1、L2、L3、L4和L5基因的位置,通过引用将其中的教导合并在此。
腺病毒基因组的每个末端都包含称为反向末端重复(ITR)的序列,其是病毒复制必需的。病毒还包含病毒编码的蛋白酶,其是加工某些结构蛋白所需的,所述结构蛋白是产生传染性病毒颗粒所需的。根据宿主细胞转导后病毒基因的表达顺序,描述了腺病毒基因组的结构。更具体地,根据转录是在DNA复制开始之前还是之后发生,将病毒基因称为早期(E)或晚期(L)基因。在转导的早期阶段,腺病毒的E1、E2、E3和E4基因被表达以使宿主细胞作好病毒复制的准备。通过删除病毒基因组的必需的早期区域1(E1),病毒可以变为复制缺陷性的。Brody et al,1994 Ann N Y Acad Sci.,716:90-101。在晚期阶段期间,接通了晚期基因L1-L5的表达,它们编码病毒粒子的结构元件。所有晚期基因都处在单个启动子的控制之下,编码的蛋白包括五邻体(L2)、六邻体(L3)、100kDa支架蛋白(L4)和纤维蛋白(L5),它们形成了新的病毒粒子,腺病毒DNA将被包裹在其中。取决于病毒的血清型,在单个宿主细胞中可以产生10,000-100,000个子代腺病毒粒子。最终,腺病毒复制过程引起细胞的裂解。
通过从公开的黑猩猩核酸序列中删除特定的核苷酸序列并插入来自其他DNA序列、对转基因的插入、表达和其他遗传操作有用的序列,构建了在此公开的复制缺陷性腺病毒载体。因此,在此描述的重组黑猩猩腺病毒可以含有来源于一种或多种黑猩猩腺病毒的腺病毒序列,或来自黑猩猩腺病毒和来自人类腺病毒的序列。可以重组地、合成地产生适合的多核苷酸序列,或可以从天然来源分离。适用于本发明的特定方面的腺病毒序列包括缺少与常见的人类血清型交叉反应的中和B细胞表位的序列。
至少,本发明的重组黑猩猩腺病毒(例如,载体)含有复制和病毒颗粒封装所需的黑猩猩腺病毒顺式作用元件,与至少一个免疫原表达盒组合。一般地,顺式作用元件侧翼于包含编码至少一个抗原的转基因的表达盒。更具体地,本发明的载体含有必需的腺病毒的顺式作用5′反向末端重复(ITR)序列(其起到复制起点的作用)、3′ITR序列、包装/增强子结构域和编码异源分子的核苷酸序列。无论所述重组载体是仅包含最小的腺病毒序列还是包含仅具有特定基因(例如,E1和/或E3或E4区域)的功能性删除的完整腺病毒基因组,本发明的载体包含黑猩猩腺病毒衣壳。
一般而言,在此公开的腺病毒载体包含复制缺陷性腺病毒基因组,其中所述腺病毒基因组不具有功能性E1基因,并包含免疫原表达盒,其包含:a)编码至少一个免疫原的核酸,针对该免疫原的免疫反应是期望的;和b)与编码所述免疫原的核酸序列可操作连接的异源(即,对于所述腺病毒序列而言)启动子;和转录终止子。
更具体地,本发明提供了由重组腺病毒基因组组成的复制缺陷性载体,所述重组腺病毒基因组缺少选自由E1、E2、E3和E4构成的组的至少一个早期基因。在一个实施方式中,通过用免疫原表达盒替换、或破坏在此公开的腺病毒分离物(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基因来制备复制缺陷性载体。例如,可以通过删除/破坏ChAd 3(SEQ ID NO:1)或ChA6(SEQ ID NO:2)的E1基因来制备载体。做为选择,复制缺陷性载体可以从在此公开的其他腺病毒分离物的任何一个来制备,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。在其他实施方式中,本发明的复制缺陷性载体包含来源于已经被任选的工程化而缺少功能性E3基因的、在此公开的ChAds之一的腺病毒基因组。要理解的是,在此公开的黑猩猩腺病毒序列可以通过完全除去早期基因或通过使基因失效或无功能来变成复制缺陷性的。
要理解的是,本发明包括了特征为具有修饰的载体,所述修饰例如破坏腺病毒表达一种或多种选定基因产物的能力的“功能性删除”。如在此使用的术语“功能性删除”宽泛地涵盖具有使特定基因产物无功能的效果的修饰。一般而言,功能性删除采取部分或全部删除腺病毒基因的形式。然而,技术人员将容易认识到,其他操作,包括但不限于进行引入移码突变的修饰也能实现功能性删除。例如,本发明的重组黑猩猩腺病毒载体可以通过导入一种修饰来成为复制缺陷性的,所述修饰被设计以干扰、或功能性删除所述病毒表达腺病毒E1A和/或E1B的能力。
公知的是,可以通过导入一种修饰来获得复制缺陷性腺病毒载体,所述修饰被设计以干扰、或功能性删除E2基因的组中一个或多个基因的表达。更详细地,可以通过钝化聚合酶基因、或前末期蛋白基因或DNA结合蛋白基因来构建复制缺陷性载体。此外,删除或钝化E4区域表达的基因是构建复制缺陷性黑猩猩Ad载体的可选择的策略。可以组合早期基因的删除或钝化来产生更为减毒的载体。做为选择,复制缺陷性ChAd载体也可以包含在其他病毒基因中的另外的修饰,例如晚期基因L1到L5。此外,可以通过组合获自不同血清型的六邻体和纤维基因来产生新的腺病毒疫苗载运体。六邻体和纤维基因混移(shuffling)策略的使用也将容许研究者改变ChAd的生物学性质和促进具有不同的趋性或具有新的血清学特征的载体的产生。
要理解的是本发明涵盖重组腺病毒载体,其包含了完整基因或其部分的删除,所述删除单独地或任意组合地有效破坏所修饰的基因的生物学活性。例如,尽管在此所示希望的是与E1基因的功能性删除相组合向载体中导入异源Ad5 E4序列,还是可以构建重组猿腺病毒,其具有E4区域表达的基因的功能性删除。做为选择,可以消除腺病毒延迟早期E3基因的功能;然而由于E3的功能不是重组腺病毒粒子的产生所必需的,不必将该基因产物重新放回以产生能够包装在本发明中有用的病毒的重组体。
在本发明的一个实施方式中,使用的复制缺陷性腺病毒载体是含有E1以及任选的E3的删除的黑猩猩C亚群腺病毒。例如,对于ChAd3,可以将适合的E1删除/破坏导入从bp460到bp 3542的区域(参考SEQ ID NO:1)。对于ChAd6,可以将适合的E1删除/破坏导入从bp457到bp 3425的区域(参考SEQ ID NO:2)。对于CV32,E1删除优选的从bp 456到bp 3416(参考SEQ ID NO:3);对于CV33,E1删除优选的从bp 456到bp 3425(参考SEQ ID NO:4)和对于CV23,E1删除优选的从bp 456到bp 3415(参考SEQ ID NO:5)。对于CV32和CV33,E3删除优选的分别为从bp 27446到bp 31911(参考SEQ ID NO:3);从bp 27146到bp 31609(参考SEQ IDNO:4)。本领域技术人员可以根据序列同源性和多重序列比对容易地确定对于其他黑猩猩分离物的等同序列。
本领域技术人员将容易地认识到,为了构建删除E1的腺病毒载体,必需考虑载体主干的结构和包含转基因的核酸序列的组成来进行许多决定。例如,研究者必需确定E1删除的大小是否适应转基因的大小。如果不适应,则必需向载体的主干中导入另外的删除。
包含转基因的核酸序列可以是基因、或基因的功能部分,一般将以表达盒的形式存在。一般地,基因表达盒包括:(a)编码感兴趣的蛋白或抗原的核酸;(b)与编码所述蛋白的核酸可操作连接的异源启动子;和(c)转录终止信号。所述核酸可以是DNA和/或RNA,可以是双链或单链的。为了在期望的宿主(例如,哺乳动物宿主)中表达可以对核酸进行密码子优化。
还必须考虑主干内要导入转基因的部位和转基因的方向来作出决定。更具体地,可以按E1平行(5′到3′转录)或反平行(相对于载体主干在3′到5′方向上转录)方向插入转基因。此外,需要鉴定合适的转录调节元件并与所述转基因可操作地连接,所述转录调节元件能够指导转基因在哺乳动物宿主细胞中的表达,载体是为所述哺乳动物宿主细胞准备用作疫苗载运体的。“可操作连接的”序列包括与被调节的核酸序列邻接的表达控制序列,和反式作用的、或在一定距离上来控制所调节的核酸序列的调节序列。
调节序列包括:合适的表达控制序列,例如转录起始、终止、增强子和启动子序列;有效的RNA加工信号,例如剪接和多聚腺苷酸信号;增强翻译效率的序列(例如,Kozak共有序列);增强蛋白质稳定性的序列和任选的促进蛋白质分泌的序列。这些和其他常见的载体元件的选择是常规的,许多适合的序列对于本领域技术人员而言是公知的。(参见,例如,Sambrook et al.和其中引用的参考文献,例如,第3.18-3.26和第16.17-16.27页,和Ausubel et al.,Current Protocols in Molecular Biology,John Wiley&Sons,NewYork,1989)。
在特定的实施方式中,所述启动子是由真核RNA聚合酶识别的异源启动子(即,对于腺病毒序列而言)。在优选的实施方式中,所述启动子是“强”或“高效”启动子。强启动子的实例是即时早期人类巨细胞病毒启动子(Chapman et al,1991 Nucl.Acids Res 19:3979-3986,通过引用将其合并)。可以使用没有(CMV)或含有内含子A序列(CMV-intA)的人类CMV启动子,尽管本领域技术人员公认的是可以使用许多其他已知的启动子,例如强免疫球蛋白或其他真核基因启动子,包括EF1α启动子、鼠CMV启动子、劳氏肉瘤病毒(RSV)启动子、SV40早期/晚期启动子和β-肌动蛋白启动子。
可以用于本发明的启动子的进一步实例是强免疫球蛋白启动子、EF1α启动子、鼠CMV启动子、劳氏肉瘤病毒启动子、SV40早期/晚期启动子和β肌动蛋白启动子,虽然本领域技术人员可以理解的是根据本发明的方法可以使用能实现预定宿主中的表达的任何启动子。启动子可以包含可调节序列,例如Tet操纵子序列。在试图抑制基因转录的情况中,例如提供了调节转录和表达的可能性的序列是有用的。
适合的基因表达盒还包含转录终止序列。优选的转录终止子是牛生长激素终止子。CMVintA-BGH终止子的启动子/转录终止组合是特别优选的,虽然也可以使用其他的启动子/终止子组合。如在此所示,50个核苷酸长度的牛生长激素终止/多聚腺苷酸信号(bGHpA)或短的合成多聚A信号(SPA)定义如下:
AATAAAAGATCTTTATTTTCATTAGATCTGTGTGTTGGTTTTTTGTGTG(SEQ ID NO:26)。
一般而言,例示了适合的终止序列。多聚A信号被插入到包含转基因的核酸序列之后和3′腺病毒ITR序列之前。
在此描述的重组腺病毒载体可以含有来源于一种或多种腺病毒株的腺病毒序列。适合的序列可以从天然的来源获得,或重组地、合成地、或通过其他遗传工程或化学方法产生。在特定的实施方式中,重组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组体。适合的非黑猩猩腺病毒序列可以从人类腺病毒株获得。例如,可以用hAd5 E4(Ad5nt 32816到nt 35619)或Ad5E4orf6(Ad5 nt 33193到nt 34077)(Ad5 GenBank登记No:M73260)替换天然的E4区域。
一般而言,由本发明的重组腺病毒载体递送的免疫原(抗原性分子)包括多肽、蛋白或酶产物,其由与一核苷酸序列组合的转基因编码,所述核苷酸序列提供了必需的调节序列来指导所述编码的产物在宿主细胞中的转录和/或翻译。转基因的组成取决于载体的预定用途。例如,如果免疫原性组合物是被设计以在哺乳动物宿主中引发特异于传染原的抗体反应或细胞介导免疫反应,则合适的是使用编码至少一个免疫原性产物的核酸序列,所述免疫原性产物预计为接受者赋予病原体特异性免疫。做为选择,如果所述组合物是制备用作癌症疫苗的,适合的转基因可以包含自体抗原例如TAA的免疫原性部分,其是根据引发足够效力的保护性免疫反应的目标来选择的,来破坏对特定TAA的宿主耐受性,和引发足以预防癌症的起始或预防肿瘤发展的、长期的(例如,记忆性)反应。因此,适合的免疫原性基因产物可以从感染哺乳动物宿主的多种病原体(例如,但不限于,病毒、寄生虫、细菌和真菌)获得,或从癌症或肿瘤细胞获得。虽然在此用特定集合的测试免疫原举例说明了本发明,要理解的是本发明不限于使用在此例示的抗原。更具体地,本发明考虑使用异源的和自体的抗原作为免疫原,包括但不限于TAA。
在一个实施方式中,本发明提供了免疫原性组合物(例如,疫苗),用于诱导针对由传染原表达的抗原(即,免疫原)的免疫反应。例如,希望的是引发针对感染人类和/或非人类动物物种的病毒的免疫反应。病毒家族的实例包括小RNA病毒科(Picornaviridae),其包括六个不同的属,例如口蹄病毒(Aphtovirus)、心脏病毒(Cardiovirus)、肠道病毒(Enterovirus)、肝病毒(Hepatovirus)、Parechovirus、鼻病毒(Rhinovirus),针对所述病毒家族的预防性和/或治疗性免疫反应是希望的。小RNA病毒的实例是:口蹄疫病毒(Foot-and-mouth disease viruses)、脑心肌炎病毒(Encephalomyocarditis viruses)、脊髓灰质炎病毒(Polioviruses)、Coxackieviruses、人类肝炎A病毒、人类parechoviruses、鼻病毒,针对所述小RNA病毒的免疫反应是希望的。杯状病毒科(Caliciviridae)包括与人类中由病毒的Norwalk群引起的流行性胃肠炎和在动物中的其他综合症有关的不同的属,所述其他综合症如在兔中与兔出血病病毒有关的出血性疾病,或在猫中由猫杯状病毒引起的呼吸道疾病。
另一个病毒家族是星状病毒科(Astroviridae),其包含从人类以及许多不同的动物物种分离的病毒,引发针对该病毒家族的免疫反应是希望的。人类星状病毒与胃肠炎和幼儿的腹泻有关。做为选择,给哺乳动物宿主赋予对病毒的披膜病毒科(Togaviridae)的成员的免疫性是希望的,其包括两个属:甲病毒属(alphavirus)和rubivirus。甲病毒属与人类和兽类疾病有关,例如关节炎(即切昆贡亚热病毒(Chikungunya virus)、辛德毕斯病毒(Sindbis virus))或脑炎(东方马脑炎病毒(Eastern Equine Encephalitis Virus)、西方马脑炎病毒(Western Equine EncephalitisVirus))。
风疹病毒提供了可选择的病毒目标,其是Rubivirus属的唯一成员,是与发烧和淋巴腺病有关的轻度皮疹疾病暴发的原因。当母亲在早期妊娠期间获得时,风疹病毒感染还与胎儿异常有关。黄病毒科(Flaviviridae)是另一个病毒家族,由三个属组成:黄病毒属、pestiviruses和肝病毒属,包括重要的人类以及动物病原体。黄病毒属成员中的许多是节肢动物传播的人类病原体,引起各种疾病包括发烧、脑炎和出血热。登革热病毒、黄热病毒、日本脑炎病毒、西尼罗河热病毒、蜱传播的脑炎病毒是主要的全球性或地域性(地方性)的病原体。Pestivirus属包括有主要是经济上的重要性的动物病原体,例如牛病毒性腹泻病毒、标准猪瘟病毒(Classical Swine Fever Virus)、边界疾病病毒(Border DiseaseVirus)。肝炎C病毒是肝病毒属的唯一成员,与急性和慢性肝炎有关。重组腺病毒表达的HCV蛋白可以引发保护性的和治疗性的免疫反应,限制在世界范围内影响17000万人的病毒感染的后果。
做为选择,来源于冠状病毒科(Coronaviridae)的成员的抗原可以由重组腺病毒载体表达以获得对感染的保护。通过用选自包括ChAd3、4、5、6、7、9、10、11、16、17、19、20、ChAd8、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82的组的、表达一种或多种SARS-CoV蛋白的一种或多种黑猩猩腺病毒进行免疫,可以获得对严重急性呼吸综合症冠状病毒(SARS-Co病毒)的保护,所述SARS-CoV蛋白无限制地包括核壳(N)蛋白、聚合酶(P)蛋白、膜(M)糖蛋白、刺突(S)糖蛋白、小包膜(E)蛋白或由该病毒表达的任何其他的多肽。包括狂犬病病毒的棒状病毒科(Rhabdoviridae)成员可以是表达病毒蛋白的重组疫苗的目标。
其他可能的目标包括Filoviridae家族,包含Ebola样病毒和Marburg样病毒属,与严重的出血热暴发有关;副粘病毒科(Paramyxoviridae)包含在人类中已知的最流行的某些病毒,如麻疹、呼吸道合胞体病毒、副流感病毒和兽医感兴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)主要由节肢动物传染到脊椎动物宿主,包含重要的人类病原体,如里夫特山谷热(Riftvalley fever)、Sin Nombre、Hantaan、Puumala病毒;沙粒病毒科(Arenaviridae)包含淋巴细胞性脉络丛脑膜炎、拉沙热、阿根廷出血热(Argentine Hemorragic fever)、玻利维亚出血热(Bolivian Hemorragic fever)病毒;Bornaviridae科包含主要在马和绵羊中引起中枢神经系统疾病的病毒;呼肠孤病毒科(Reoviridae)包括轮状病毒,世界范围内的婴儿和幼儿中严重痢疾性疾病的最重要原因,可以感染人类和其他哺乳动物的环状病毒(蓝舌病、兽疫流行性出血病病毒);逆转录病毒科(Retroviridae),病毒的一个大组,包含重要的人类病原体如人类免疫缺陷性病毒1和2(HIV-1和HIV-2)和人类T细胞白血病毒1型和2型(HTLV1和2),以及非人类慢病毒,例如感染绵羊和山羊的Maedi/Visna viruses,感染马的马传染性贫血病毒,感染牛的牛免疫缺陷病毒,感染猫的猫免疫缺陷病毒;多瘤病毒科(Polyomaviridae)包括小的DNA致癌病毒,典型病毒是分别感染小鼠和恒河猴的多形瘤和SV40(从人类患者分离了与SV40近相关的BK和JC病毒);乳头状瘤病毒科(Papillomaviridae)由一组DNA病毒组成,所述病毒感染高等脊椎动物包括人类,产生疣和湿疣。乳头状瘤病毒感染与人类和动物中的癌症发展有关。人类乳头状瘤病毒与子宫颈癌、阴道癌和皮肤癌有关。疱疹病毒科(herpesviridae)包括一些亚科,在其中分类了许多人类和其他哺乳动物的重要病原体。抗原的适合的来源可以是但不限于单纯性疱疹病毒1和2,水痘-带状疱疹病毒、Epstein-Barr病毒、细胞巨化病毒、人类疱疹病毒6A、6B和7、卡波西肉瘤相关疱疹病毒。抗原的进一步适合的来源是痘病毒科的成员,如猴痘病毒、Molluscumcontagiusum病毒、天花病毒;肝炎B病毒,肝病毒科的典型成员,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。
本发明的腺病毒载体还适合于制备免疫原性组合物,所述免疫原性组合物被设计以在人类或动物中刺激针对非病毒病原体表达的蛋白的免疫反应,所述病原体包括细菌、真菌、寄生虫病原体。例如在此公开的载体可以用于制备针对,但不限于:Staphylococcusaureus、Streptococcus pyogenes、Streptococcus pneumoniae、霍乱弧菌(Vibriocholerae)、破伤风杆菌(Clostridium tetani)、Neisseria meningitis、Corynebacteriumdiphteriae、结核分枝杆菌(Mycobacteria tuberculosis)和麻风杆菌(leprae),Listeriamonocytogenes和Legionella pneumofila的疫苗。希望制备预防性或治疗性疫苗的真菌和哺乳动物寄生虫的实例包括:白色念珠菌(Candida albicans)、烟曲菌(Aspergillusfumigatus)、Histoplasma capsulatum、Plasmodium malariae、Leishmania major、Trypanosome cruzi和brucei、Schistosoma haematobium、mansoni和japonicum;Entamoeba histolytica,和已知与人类丝虫病有关的Filaria的许多种类。
癌症一般涉及编码多肽的基因的失调,所述多肽有助于维持细胞周期或控制细胞增殖(例如,生长因子、致癌基因、受体和肿瘤抑制物)。涉及癌症的许多基因的产物在各种各样的肿瘤细胞表面表达。在人类和动物癌症中已经鉴定了可被T和B淋巴细胞识别的多种肿瘤抗原。适用于抗癌疫苗试验的极大多数肿瘤相关抗原(TAA)被描述为“自体抗原”,因为除了在肿瘤细胞上表达之外,它们还在正常的组织上和/或在胎儿发育期间表达。目标人群对TAA的免疫耐受可以解释为什么许多癌症疫苗被证实是无效的。
肿瘤抗原可以通过正常细胞基因的致癌突变体来产生,改变的原癌基因或肿瘤抑制物基因例如,Ras、p53或Bcr-Abl蛋白是可以刺激T/B细胞反应的改变的细胞蛋白的实例。肿瘤抗原可以是在肿瘤细胞中过量表达的正常细胞蛋白(酪氨酸酶、GP100、MART通常在黑素细胞中以低水平表达,在黑素瘤中过量表达),或在肿瘤细胞中异常表达的正常细胞蛋白(MAGE、BAGE、GAGE在黑素瘤和许多癌中表达,但是在睾丸和胎盘中正常表达)。肿瘤抗原可以是致癌病毒的产物:由宫颈癌表达的乳头状瘤病毒E6和E7蛋白;由EBV+淋巴瘤和鼻咽癌产生的EBV EBNA-1蛋白;在SV40诱导的实验肿瘤中的SV40T抗原。癌胎抗原(oncofetalantigens)在癌细胞和正常发育的(胎儿)组织中高水平表达,但不在成年人组织中表达。癌胚抗原(CEA)和甲胎蛋白(AFP)是良好表征的癌胎抗原的实例。
新近的证据支持了能引发免疫反应的TAA的存在,因而使这类抗原成为疫苗疗法的适合的免疫原。然而,作为一类抗原,TAA是非常不好的免疫原,在T细胞发育期间高度特异于TAA的T细胞不是被删除了就是被无反应化了。因此,预期的是,携带肿瘤的宿主对特定TAA的免疫反应是极其微弱的。由于破坏对目标TAA的宿主耐受性的内在需要,实验性的临床疫苗研究特别集中于开发能增强TAA特异性T细胞反应的免疫策略。一般地而言,有效的癌症疫苗必须克服免疫耐受性并且增强宿主的免疫反应到预防性和/或保护性的水平。在许多实验性疫苗研究中已经将抗肿瘤效果与对TAA的T细胞反应相关联。
在可选择的实施方式中,本发明考虑能用于诱导针对肿瘤抗原的免疫反应的免疫原性组合物(例如,癌症疫苗)。适合的组合物将含有包含编码肿瘤抗原的核酸序列的重组黑猩猩腺病毒,和生理学上可接受的载运体。在特定的实施方式中,盒的编码序列元件可以编码单个免疫原,例如,来源于自体抗原的免疫原性肽序列,例如肿瘤相关抗原。在某些实施方式中,编码免疫原的核酸序列(例如,转基因)可以是为在特定哺乳动物物种中的表达优化了的密码子。在其他实施方式中,编码序列可以编码超过一个免疫原,例如一种或多种密码子优化的肿瘤抗原。例如,利用所公开的腺病毒载体的癌症疫苗可以编码自体抗原的组合,自体抗原例如:HER2/neu、CEA、Hepcam、PSA,PSMA、端粒酶、gap100、Melan-A/MART-1、Muc-1、NY-ESO-1、存活蛋白、溶基质蛋白酶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。
有效的癌症疫苗的开发需要鉴定能在接种的患者中引发抗原特异性免疫的策略和产生在主动免疫结束后能够留存的免疫反应。策略的成功将取决于针对目标抗原的可测量免疫反应是否与针对癌症的发生或复发的保护作用相关。已经显示了细胞介导的免疫和体液免疫的效应机制都能杀死肿瘤细胞。然而,来自实验系统的数据表明,抗原特异性T细胞是消除肿瘤细胞的最强大的免疫机制。效应T细胞对肿瘤特异性抗原(例如,TAAs)的识别预计可容许TAA象肿瘤排斥抗原一样起作用。公开的研究表明,刺激CD8+和CD4+辅助T细胞反应对于达到最优的肿瘤清除是重要的((Greenberg,P.D.(1991)Adv.Immunol.49:281-355;Pardoll,D.M.et al.(1998)Curr.Opin.Immunol.10:588-94)。临床反应(即,效力)已经与分泌干扰素γ的细胞毒性T细胞的增加相关联。分析方法的出现,例如在此使用的ELISPOT分析,以展现当前疫苗载运体的效力,容许研究者测量对免疫接种方式的T细胞反应,从而便于癌症疫苗的开发。
癌症疫苗可以是预防性或治疗性的。癌症疫苗的预防性用途的一般假定是,在携带肿瘤的受试者中TAA是极其弱的免疫原或功能上无免疫原性的。更具体地,在癌症免疫学领域,在患有癌症的患者中疫苗可以用作免疫疗法。因此,可以设计癌症疫苗来引发针对TAA的免疫反应,所述TAA由先存的肿瘤或恶性肿瘤表达。因而,在特定的实施方式中,治疗性癌症疫苗意图用于携带肿瘤的患者,其发展了对常规治疗方式的抗性,或在常规治疗后有发展出复发的高可能性。
腺病毒的高免疫原性使得腺病毒载体对用于疫苗载运体的情况是特别好的候选者,所述疫苗载运体被设计以破坏宿主对自体抗原的耐受性。在自体免疫疾病中首先描述的表位或决定簇传播的现象,已经与MHC I类和MHC II类限制性反应相关联,并与HER-2/neu蛋白特异性T细胞免疫的发展相关联。表位传播代表了对免疫原性蛋白的特定部分的免疫反应的产生,随后是免疫天然传播到存在于同一蛋白上的其他抗原决定簇。例如,Disis等在84%的患有过量表达HER-2/neu的恶性肿瘤的患者中观察到表位传播,所述患者被施用了疫苗,所述疫苗包含与粒细胞-巨噬细胞集落刺激因子混合的、来源于HER-2蛋白的可能的T辅助表位的肽(J.Clin.Oncol.(2002)20(11):2624-2632)。重要地,表位传播与HER-2/neu蛋白结构域反应的产生有关,并提示了有效地绕过了免疫耐受性的免疫。
适用于在此公开的腺病毒载体和方法作为癌症疫苗的目标的TAA应当具有许多特征。例如,目标TAA必须具有有利的表达分布型,意味着与正常组织相比,在肿瘤或恶性组织中它应当优先地表达或过量表达。此外,因为在肿瘤发生中起作用的TAA更有可能在癌症发展的不同阶段期间保留,适合的目标TAA还应当在肿瘤发展和转移的整个阶段保持。适合的目标TAA还应当在肿瘤内同质地表达。第三,适合的目标TAA必需不经受绝对的免疫耐受性。更具体地,必须有某些证据,可以识别感兴趣的TAA并对其进行应答的T细胞没有从宿主的T细胞库中完全地删除(Berinstein,N.L.,J.Clin.Oncol.29(8):2197(2002)。
癌胚抗原(CEA)具有许多特征,使它成为用作抗癌疫苗的目标抗原的吸引人的TAA。它是Ig超家族的成员,所述Ig超家族的特点在于有利的表达模式。它在超过50%的所有人类癌症中表达,并与肿瘤发生过程有关,这表明它的表达在整个癌症发展过程中可能是被选择的和保守的。此外,已经证明对CEA的免疫耐受性不是绝对的。公开的研究确定了,人类T细胞可以识别表达CEA的癌细胞,成为对表达CEA的癌细胞有活性的,并裂解表达CEA的癌细胞(Berinstein,N.L.,J.Clin.Oncol.29(8):2197(2002)。例如,用表达CEA的重组牛痘病毒免疫患者,结合随后的基于肽的体外刺激,产生了能裂解自体肿瘤的CD8+MHC限制性CTL(Tsang,K.Y.et al.J.Natl.Cancer Inst.,(1995)87:982-990)。另外地,报道了手术后用重组CEA免疫结肠直肠癌患者诱导了针对CEA的弱的抗体和细胞反应(Samanci,A.,etal.(1998)Cancer Immunol.Immunother.47:131-142.)。进一步的,向诊断患有结肠直肠癌的患者施用抗CEA抗独特型抗体,产生了抗CEA抗体和独特型特异性T细胞增殖(Foon,L,A.et al.(1995)J.Clin.Invest.,96:334-342)。文献还表明,可以用几种不同的疫苗接种方法克服癌症患者中对CEA的耐受性(即,用重组CEA或重组正痘或禽痘一CEA病毒疫苗接种,施用抗独特型抗体,用CEA激动剂表位脉冲树突状细胞)。
CEA是癌胎糖蛋白(oncofetal glycoprotein),其在正常胎儿结肠中表达,在正常的结肠粘膜中以小得多的程度表达。它还在大多数腺癌,特别是结肠、胰腺、乳房、肺、直肠和胃的腺癌中过量表达。许多结肠直肠癌症和一些癌瘤产生在血清中可测量的高水平的CEA,这使之成为最广泛使用的恶性肿瘤的血清学标记,特别是在患有结肠直肠癌的患者中。
提供了用于本发明的组合物和方法的适合的免疫原的第二种TAA是HER2/erb-2(也称为neu)原癌基因的产物。象CEA一样,HER2/neu具有有利的表达模式,并且不经受绝对耐受性。更具体地,在正常成年人各种组织,包括皮肤和乳房,和胃肠道、生殖道、和泌尿道的组织的上皮细胞中,检测到低水平的HER2/neu转录产物表达和185kD的多肽产物;在胚胎发育期间在相应的胎儿组织中检测到更高水平的表达(Press et al.,Oncogene 5:953-962(1990)。几个系列的证据暗示了在人类乳房、肺、前列腺、卵巢、子宫内膜和结肠直肠肿瘤中HER-2的扩增与致瘤性转化之间的联系(Disis and Cheever,Adv.Cancer Research71:343-371(1997)。一般而言,HER2/neu的过量表达与癌症患者的不良预后和较高的复发率有关(Slamon et al.,Science 244:707-712(1989)。因而,特异于HER-2/neu蛋白的疫苗在许多不同人类恶性肿瘤的疾病复发预防方面具有广泛的应用和实用性。
HER2/neu编码具有内在的酪氨酸激酶活性并显示了与表皮生长因子(EGF)受体的广泛同源性的跨膜糖蛋白(Akiyama,T et al.,(1986)Science 232:1644-1646)。使用HER2作为癌症免疫疗法的靶点的最初的临床研究之一,采用了HER-2特异性单克隆抗体Herceptin用于乳腺癌的治疗(Goldenberg MM(1999)Clin.Ther.21:309-318)。这引起了随后的努力,其集中于使用HER-2作为免疫系统的T细胞支路(arm)的靶点来引发有效的抗瘤反应,包括使用包含HER-2结构域的重组融合蛋白来激活自体抗原递呈细胞。公开的报道确定了,患有表达neu的乳腺和卵巢癌症的许多癌症患者产生了针对HER2/neu癌基因的蛋白产物的免疫反应(例如,产生抗原特异性抗体和T细胞)。
重组腺病毒序列、转基因和其他载体元件装配到各种中间质粒和穿梭载体中,使用所述质粒和载体来产生重组病毒粒子,都可以使用本领域技术人员公知的标准教科书中描述的常规技术来实现(Sambrook et al,Molecular Cloning:A Laboratory Manual,2ndEd.,Cold Spring Harbor Press,Cold Spring Harbor,NY(1989)。这种技术包括但不限于,常规的cDNA克隆技术、使用来源于腺病毒基因组的重叠寡核苷酸序列、同源重组、聚合酶链式反应、标准转染技术、琼脂覆层中的病毒斑块,和其他相关的方法。
为了帮助在原核细胞中制备多核苷酸,常常制备腺病毒载体的质粒型式(腺病毒前质粒)。腺病毒前质粒含有腺病毒部分和质粒部分。腺病毒部分与本发明的腺病毒载体(含有无功能的或删除的E1和任选的E3区域的腺病毒序列)中包含的腺病毒部分和侧翼是方便的限制性位点的免疫原表达盒基本上相同。
腺病毒前质粒的质粒部分常常含有处在原核启动子的转录控制下的抗生素抗性标记,从而抗生素的表达不会在真核细胞中出现。可以使用氨苄青霉素抗性基因、新霉素抗性基因和其他药学上可接受的抗生素抗性标记。为了有助于在原核生物中通过发酵高水平产生多核苷酸,有益的是腺病毒前质粒含有原核复制起点并且是高拷贝数的。许多商业上可获得的原核克隆载体提供了这些益处。希望的是除去非必需的DNA序列。同样希望的是所述载体不能在真核细胞中复制。这将多核苷酸疫苗序列整合到接受者的基因组中的风险最小化。当希望将多核苷酸的表达限制到特定的组织类型时,可以使用组织特异性启动子或增强子。
可以通过使用腺病毒主干DNA和合适的穿梭载体(被设计以靶向特定的删除并将期望的限制性位点掺入产生的质粒中)进行同源重组产生腺病毒前质粒(包含具有期望的删除和插入的复制缺陷性腺病毒的基因组的质粒)。在这个过程中使用的穿梭载体可以使用本领域广泛了解和理解的一般方法来产生,例如,考虑期望的删除来对腺病毒末端进行PCR,将各个片段顺序克隆到合适的克隆质粒中。然后可以消化腺病毒前质粒并通过磷酸钙共同沉淀或其他合适的方法转染入补足细胞系。然后发生病毒复制和扩增,一种由于显著的细胞病变效果而变明显的现象。然后在病毒复制完成之后收获感染的细胞和培养基(一般地,转染后7-10天)。
一般而言,在构建和装配期望的腺病毒前质粒之后,通过转染表达腺病毒E1的人类细胞系将腺病毒前质粒营救为病毒。在包装细胞系和载体的病毒基因之间的补充性允许载体中的腺病毒-转基因序列被复制并包装到病毒颗粒衣壳中,引起重组腺病毒的生产。可以通过本领域技术人员已知的各种方法的任何一种,来分离和纯化产生的病毒,用于本发明的方法。
对本领域技术人员显而易见的是,当向病毒载体中导入一个或多个选定的黑猩猩腺病毒基因的删除时,可以在生产过程期间通过在生产细胞系中存在的序列来提供被删除的基因产物的功能。因而,可以通过永久转化的细胞系来提供所操作的基因的功能,所述细胞系的特征是某些或全部腺病毒功能,所述功能是包装所需的但在载体中是无功能的(例如,E1A、E1B、E2A、E2B、E4的任何一个)。做为选择,可以用包含必需基因的构建体来感染或短暂地转染适合的细胞以提供所述功能,来将必需的腺病毒功能提供给适合的包装细胞系。
因此,本发明还提供了在表达E1的人类细胞系中生产黑猩猩腺病毒载体的方法。更具体地,所公开的载体可以在E1补足细胞系中增殖,包括已知的细胞系293和PER.C6TM。这些细胞系都表达腺病毒E1基因产物。在1997年1月3日公开的WO 97/00326中描述了PER.C6TM,通过引用将其合并在此。它是用E1基因片段转导的原代人类成视网膜细胞系,所述E1基因片段补足复制缺陷性第一代腺病毒的产生,但被设计以防止通过同源重组产生有复制能力的腺病毒。在Graham et al(1977)J.Gen.Virol 36:59-72中描述了293细胞,也通过引用将其合并在此。本领域技术人员将认识到术语“第一代腺病毒”是指复制缺陷性腺病毒,其是E1区域无功能的或删除了E1区域的,并任选的是E3区域无功能的或删除了E3区域。
意图用作临床试验中的疫苗组合物的复制缺陷性腺病毒载体的批次应当经证明是无RCA的(Fallaux,F.J.et al(1998)Human Gene Therapy,9:1909-1917)。实际上,这是劳动密集的过程,需要建立和使用昂贵的筛选程序。本领域技术人员将认识到,高频率的RCA产生不仅引起生产的批次的高失败率,还严重地限制了规模扩大的努力。消除载体的核苷酸序列和存在于辅助生产/包装细胞系的基因组中的腺病毒序列之间的同源性,将消除生产的载体批次被同源重组产生的RCA污染的可能性。
一般地,重组复制缺陷性腺病毒载体在提供E1基因产物in trans的细胞系中增殖。当载体来自相同的或非常相似的血清型时,提供必需的E1基因产物in trans是非常有效的。例如,公知的是删除了E1(即,ΔE1)的C群血清型(Ad2和Ad5)载体,可以在含有并表达Ad5 E1区域的293或PER.C6细胞中增殖。然而,已经观察到,存在于293和PER.C6生产细胞中的Ad5E1序列可能不总是完全地补足非C群血清型的复制。因此,C亚群以外的删除E1的血清型,例如,来自A、B、D、E和F亚群的那些,在293或PER.C6细胞中可能以比相应wt病毒更低的效率复制,或可能根本不复制。这可能是由于Ad5(C亚群)E1 B 55K基因产物不能够建立与非C群血清型的E4 orf6基因产物的功能性相互作用。
在表达Ad5 E1的细胞中复制效率的降低根据不同亚群的载体而变化。虽然来自D和E亚群腺病毒的ΔE1载体可以以可变的效率在293和Per.C6TM细胞中被营救(rescue)和增殖,B亚群ΔE1载体的增殖被完全地削弱了(Vogels R,et al.(2003)Aug.Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination:efficient human cell infection and bypass of preexisting adenovirusimmunity.J Virol.77(15):8263-71).
尽管Ad5 E1b 55k和载体表达的E4 orf6蛋白之间的相互作用在相同亚群的成员内是保守的,当表达非C血清型的E4 orf6蛋白时它可能不是足够稳定的。E1B-55K/E4-orf6复合物的这种低效或不稳定形成引起了ΔE1载体的降低的增殖的缺乏。因此,已经经验性确定的是,为了成功地和有效地营救B群血清型的重组腺病毒,需要产生表达感兴趣血清型的E1区域的细胞系。在表达Ad5E1的细胞如293或Per.C6TM中,表达可以限于E1b 55K蛋白。做为选择,可以修饰适合的Ad5E1表达细胞系以便除了Ad5E1之外还表达完整的Ad5 E4区域(或仅E4 orf6)。表达Ad5 E1和orf6的细胞系的产生,在补足可选择的腺病毒血清型方面是有用的;参见,例如,Abrahamsen et al.,1997J.Virol.8946-8951。E4(orf6)掺入到Ad5补足细胞系是已知的,产生in trans提供血清型特异性E1基因产物的血清型特异性细胞系也是已知的。做为选择,非C群载体增殖的效率可以通过用Ad5 orf6取代天然的E4区域修饰病毒主干来改善。用来自Ad5或其他C亚群病毒(Ad1、Ad2、Ad6)的orf6仅替换天然的orf6也可以得到类似的结果。美国专利No.5,849,561公开了在还表达Ad5-E4基因的部分的Ad5-E1补足细胞系中补足删除E1的非C群腺病毒载体。
授权给Vigne等的美国专利No.6,127,175公开了稳定转染的哺乳动物细胞系,其表达腺病毒的E4区域的一部分,优选的是orf6/orf6/7。这种细胞系对于补足E4区域中的重组Ad基因组缺陷是有用的。
包含所公开的腺病毒载体的组合物,包括疫苗组合物,是本发明的重要的方面。这些组合物可以以预防性或治疗性的设置施用给哺乳动物宿主,优选的人类宿主。可能的宿主/接种者包括但不限于灵长类和特别是人类和非人灵长类,并包括有商业或驯养的兽医学重要性的任何非人哺乳动物。包含重组黑猩猩腺病毒载体的组合物可以单独施用或与其他基于病毒或非基于病毒的DNA/蛋白疫苗组合施用。它们也可以作为更广阔的治疗方式的部分来施用。
在本发明的特定实施方式中,所公开的载体可以用于被设计以破坏宿主对自体抗原或肿瘤相关抗原的耐受性的免疫方案。许多TAA的鉴定已经允许了开发用于癌症治疗的主动疫苗接种方法。被加工和呈递的细胞表面抗原和细胞内抗原都提供了有用的靶点。一般而言,所公开的破坏宿主对自体抗原的耐受性的方法包括:(a)通过施用包含第一ChAd载体或质粒载体的第一疫苗组合物来刺激对自体抗原的抗原特异性反应,所述第一ChAd载体或质粒载体携带编码自体抗原的核苷酸序列,针对所述自体抗原的抗原特异性免疫反应是期望的,和(b)通过施用包含不同的血清型的重组ChAd载体的第二疫苗组合物来维持和扩展(a)的免疫反应,所述重组ChAd载体含有其基因组E1基因的至少一个功能性删除,并且在E1基因的位置上含有包含启动子的序列,所述启动子能指导编码在激发步骤中释放的相同自体抗原的DNA的表达,从而宿主产生具有破坏对自体抗原的耐受性的效果的免疫反应。
因此,技术人员可以使用这种公开内容来设计可能适用于破坏宿主耐受性的几种不同的免疫方案。例如,可能的是使用一种方案,其中第一或激发免疫包含质粒DNA,所述质粒DNA编码特定的自体抗原,例如TAA,任何随后的免疫包含ChAd载体。包含编码自体抗原的核苷酸序列的质粒DNA序列可以在一次或多次注射中,有或者没有电刺激地、肌肉内地递送。例如,基于通过电穿孔多次(例如,3或4或5次)肌肉注射编码TAA的质粒DNA,随后一次或多次肌肉注射包含编码相同TAA的转基因的ChAd载体的免疫方案,被在此公开和要求权利的一般方法包括。
做为选择,破坏耐受性的适合的方案可以包括用包含编码自体抗原的转基因的ChAd或hAd载体进行一次或多次激发免疫,随后用相同的ChAd载体或已知与用于激发免疫的载体不是交叉反应性的、不同的ChAd载体进行一次或多次强化免疫。例如,使用ChAd3激发和用ChAd6进行强化,或用ChAd3激发随后用ChAd6和ChAd9进行强化的免疫方案可以用于破坏宿主耐受性。在特定的实施方式中,本发明考虑使用包含选自以下构成的组的至少一个肿瘤相关抗原的自体抗原:HER2/neu、CEA、EpCAM、PSA、PSMA、端粒酶、gap100、Melan-A/MART-l、Muc-1、NY-ESO-1、存活蛋白、溶基质蛋白酶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。在特定的实施方式中,本发明提供了通过向患有癌症的哺乳动物递送编码TAA的重组黑猩猩腺病毒、诱导针对特异于选定恶性肿瘤的肿瘤相关抗原的免疫反应(例如,体液或细胞介导的)的方法。在本发明的这个方面的优选实施方式中,引发的免疫反应构成了以抗原特异性CD4+和CD8+T细胞的产生为特征的免疫反应。
本发明的免疫原性组合物可以以预防性或治疗性的设置(setting)施用给哺乳动物宿主,优选的人类宿主。可能的宿主/接种者包括但不限于灵长类和特别是人类和非人灵长类,并包括有商业或驯养的兽医学重要性的任何非人哺乳动物。包含重组黑猩猩腺病毒载体的组合物可以单独施用或与其他基于病毒或非基于病毒的DNA/蛋白疫苗组合施用。它们也可以作为更广阔的治疗方式的部分来施用。用于本发明的方法的适合的组合物可以包含本发明的重组病毒载体,结合生理学上可接受的成分,例如缓冲液、生理盐水或磷酸盐缓冲盐水、蔗糖、其他盐和聚山梨酸酯。在肌肉注射时它不引起组织刺激。优选的是冷冻待用的。任选的,本发明的疫苗组合物可以配制为含有其他成分,例如但不限于,佐剂、稳定剂、pH值调节试剂,或防腐剂。这些成分是本领域技术人员公知的。
预想的是,本发明的重组黑猩猩腺病毒以“有效量”施用给人类或兽医学上的宿主,所述“有效量”是重组病毒的数量,其是有效的以在选定的施用途径下转导宿主细胞并提供转基因的足够表达水平来引发给接受者/疫苗接种者(vaccine)赋予治疗效益或保护性免疫的免疫反应。
导入疫苗接受者的疫苗组合物中病毒粒子的数量取决于使用的转录和翻译启动子的强度和表达的基因产物的免疫原性。一般地,免疫或预防有效剂量的1×107到1×1012个粒子(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),和优选的约1×1010到1×1011个粒子直接施用到肌肉组织中。皮下注射、皮内导入、压过皮肤,和其他施用模式,例如腹膜内的、静脉内的或吸入递送也是考虑的。
本发明的重组黑猩猩腺病毒载体可以单独地、作为混合形式的激发/强化疫苗接种方式的部分、或在基于不同载体血清型的多次注射的组合的接种方式中来施用。一般地,将包含至少一个免疫原的激发剂量施用给哺乳动物宿主,所述哺乳动物宿主需要针对特定病原体或自体抗原的有效免疫反应。这种剂量有效地激发免疫反应,从而在随后的抗原鉴定中,宿主能够立即产生针对该免疫原的增强的或强化的免疫反应。利用用于激发和强化的可选择制剂的混合形式疫苗接种方案可以引起增强的免疫反应。激发一强化施用一般包括激发(通过病毒载体、质粒、蛋白,等)受试者至少一次,容许经过预定长度的时间,然后强化(通过病毒载体、质粒、蛋白,等)。通常采用多次免疫,一般1-4次,尽管可以使用更多次数。激发和强化之间的时长一般可从约四个月到一年,虽然本领域技术人员理解的是可以使用其他的时间范围。在中和免疫性变得明显之前,每种载体的多次注射可以在约2周的时间范围(time frame)内施用。
在本发明的某些实施方式中,给予疫苗超过一次的腺病毒疫苗载体施用,可以以伴有质粒疫苗的施用的方式来给予。与在此公开的载体组合使用的适合的质粒疫苗包括编码至少一个免疫原的质粒,针对所述免疫原的激发的或强化的免疫反应是期望的,和异源启动子,其能够指导编码免疫原的核酸序列的表达,可操作地与免疫原编码序列连接,和转录终止序列。
例如,可以使用一种剂量给药方式,其利用不同血清型的重组复制缺陷性黑猩猩腺病毒载体的多次注射。做为选择,可以给予个体第一剂量(即,激发剂量)的质粒疫苗,和第二剂量(即,强化剂量),其包含复制缺陷性重组黑猩猩腺病毒载体,所述载体包含在质粒疫苗中递送的相同免疫原的编码序列。做为选择,可以给予个体第一剂量编码至少一个免疫原的人类腺病毒疫苗载体,随后是第二剂量,其包含在此公开的复制缺陷性重组黑猩猩腺病毒载体,所述载体包含与在激发剂量中递送的相同的免疫原的编码序列。在第二个可选择的实施方式中,可以首先施用包含本发明的载体的疫苗组合物,随后施用质粒疫苗。在这些实施方式的任何一个中,可以以病毒载体或质粒形式给予个体多剂量的相同免疫原。可以有预定的最小时间量,来分隔施用。
除了通过本发明的重组复制缺陷性黑猩猩腺病毒载体递送感兴趣的单个蛋白或抗原之外,可以通过独立的运载体(vehicle)或通过相同的运载体来递送两种或多种蛋白或抗原。可以将多个基因/功能等同物连接到适当的穿梭质粒,来产生包含多个开放阅读框的腺病毒前质粒。多个基因/功能等同物的开放阅读框可以可操作地连接到不相同的启动子和转录终止序列。
如在此所示,适合的免疫方式可以采用不同的腺病毒血清型。这种方案的一个实例是包含第一血清型,例如ChAd3或ChAd6的重组腺病毒载体的激发剂量,随后是包含第二血清型的重组黑猩猩腺病毒载体的强化剂量。在可选择的实施方式中,激发剂量可以包含独立的腺病毒运载体的混合物,每种腺病毒运载体包含编码不同蛋白/抗原的基因。在这种情况下,强化剂量也可以包含载体的混合物,每种载体包含编码独立的蛋白/抗原的基因,条件是强化剂量施用重组病毒载体,所述重组病毒载体包含编码与激发剂量中所递送的相同或相似组的抗原的遗传物质。可以进一步组合这些多基因/载体的施用形式。进一步处在本发明的范围内的在于,组合的用药方式,其包括来自特定抗原的多个但各不相同的成分。
使用不被针对人类载体的病毒元件的先存免疫性中和的、来源于黑猩猩腺病毒的重组载体,提供了对于使用人类Ad载体作为疫苗载运体的替代性选择。由于腺病毒是高度免疫原性的,腺病毒载体对用于疫苗载运体的情况是特别好的候选者,所述疫苗载运体被设计以破坏宿主对自体抗原的耐受性。此外,以能够与人类病毒相比较的效率、在人类细胞中,特别是在Per.C6TM细胞系中增殖黑猩猩病毒的能力,从调节的角度和从治疗剂或疫苗的大规模产生的角度都提供了相当大的益处。因此,本发明提供了一组黑猩猩腺病毒序列、载体和质粒,容许制备重组病毒,所述重组病毒可单独地或组合地用作遗传疫苗接种的疫苗载运体。
为了描述和公开可能与本发明相联系使用的方法和材料,在此提及的所有出版物通过引用合并。在此的任何内容都不能解释为承认本发明没有资格根据在先的发明在日期上早于这种公开。
参考附图描述了本发明的优选的实施方式,要理解的是本发明不限于这些明确的实施方式,由本领域的技术人员可以实行各种改变和修改而不背离如附随的权利要求中所定义的本发明的范围和精神。
以下实施例说明、但不限制本发明。
实施例1:ChAds黑猩猩腺病毒分离物的分离、克隆、测序和表征
在NIRC(New Iberia Research Center 4401 W.Admiral Doyle Drive NewIberia,LA′70560),在病毒转运培养基(VTM;Microtest M4-R Multi Microbe TransportMedium,Remel Inc.)中收集大便样本,然后冷冻,或直接在-70℃冷冻。样本保持冷冻在<-70℃,直到对它们进行处理用于接种到细胞培养物中。在那时,将样本解冻,然后在过量的冷却的病毒转运培养基中涡旋。在样本分离成悬浮液之后,在1500-1800rpm将它们离心10分钟。将上清液连续过滤通过0.8和0.2μm针筒过滤器,然后将过滤了的材料接种到细胞培养物中(200-250μL进入壳瓶(shell vial),200-300μL进入试管培养物)。将每种处理过的样本接种到播种了293细胞或A549细胞的试管培养物和壳瓶培养物中。
每次接种一组样品时制备对照(阳性和阴性)培养物。一旦已经接种了set-up中的所有壳瓶,将它们在室温下以2000rpm(900×g)离心60±10分钟。在转子停止旋转后立即从离心机取下小瓶以防止培养物中的热破坏。离心之后,从壳瓶中吸出接种物,在每个小瓶中使用新鲜的无菌Pasteur吸管以防止交叉污染。每次用1.0mL新鲜培养基洗涤培养物三次。洗涤三次之后将新鲜培养基(1.0mL)移液到每个小瓶中,将壳瓶置于孵化器中35-37℃三到四天(约96hr)。
在培养期结束时,从培养物吸出上清液,用免疫荧光分析(IFA)缓冲液每次使用约1.0mL缓冲液洗涤每个小瓶中的细胞层两次。通过向每个小瓶添加1.0mL冷却的丙酮(2-8℃10分钟)来固定细胞。用与壳瓶盖片相关的样本标识数字标记清除了丙酮的载玻片。使用初级小鼠抗腺病毒抗体[MAB8052,Chemicon]处理壳瓶盖片进行腺病毒感染的细胞的荧光标记。借助于荧光显微镜评估载玻片。使用10×物镜扫描每个制备物,记录免疫荧光覆盖加样孔的程度(1+到4+)。使用40×物镜证实特异性免疫荧光的存在或不存在。如对壳瓶所描述的按相同的顺序对试管培养物进行接种(例如,首先是阴性对照、随后是临床样本和阳性对照)。容许接种物在36-38℃吸附60-120分钟。在吸附期之后,从试管中吸出样本/对照,用新鲜培养基替代。
接种后三到四天,和此后的一周一次,从培养试管中吸出培养基,用1.5mL新鲜培养基替换。接种后的至少21天内至少每隔一天视觉上监视培养试管的CPE。用黑猩猩样本接种的培养物与对照进行比较,并通过观察CPE程度评级。14天后没有显示CPE的培养物转移到新鲜的试管培养物;21天后CPE阴性的培养试管考虑为阴性的。具有3-4+CPE的培养试管进行涡旋10秒。使用无菌的1.0mL血清学吸管从试管的壁上刮下细胞,悬浮在培养物上清液中。之后用样本标识数字和日期标记5mL扣帽试管(snap cap tube),保存在-70℃。将500μL细胞悬液从培养试管转移到扣帽试管中,在2-8℃保存至多一天,直到使用间接免疫荧光抗体技术进行处理来检测腺病毒(相当于染色壳瓶的步骤)。
黑猩猩腺病毒扩增
野生型黑猩猩腺病毒CV32、CV33、CV23和CV68购自ATCC(ATCC登记号:CV32,VR-592;CV-33,VR-593;),或购自Esoterix Inc.Austin,Texas,原始分离物如下通过使用表达E1的人类细胞系PER.C6TM或293来增殖。简要地,将细胞培养在Dulbecco′s ModifiedEagles培养基(DMEM;GibcoBRL,Life Technologies)中,其补充有10%胎牛血清(FBSGibcoBRL,life Technologies)、1%青霉素-链霉素、2mM谷氨酰胺和10mM MgCl2(Per.C6TM)。在补充有5%马血清(GibcoBRL,Life Technologies)的DMEM中进行腺病毒感染。当100%的细胞展现出病毒诱导的细胞病变效应(CPE)时,收集感染的细胞和培养基,通过三个循环的冷冻和解冻来裂解。
在扩增的第一次传代之后,通过感染播种在96孔平板中的293细胞来克隆所有野生型黑猩猩腺病毒(CV)成品(stocks)。通过对在病毒扩增的第一次传代获得的细胞溶胞产物进行限制稀释,来进行病毒克隆。挑取五个分离的克隆并顺序地增殖。在扩增的3-4次连续传代之后,在种植在5个双层细胞工厂(NUNC)(200百万细胞/细胞工厂)的细胞上进行大规模的腺病毒制备。通过在氯化铯密度梯度上的两个超离心步骤从细胞溶胞产物获得纯化的病毒粒子。
病毒基因组DNA的测序
通过在1%SDS-TEN中用蛋白酶K(0.5mg/ml)消化(55℃2小时),从3×1012pp的纯化的病毒制品分离基因组DNA。在苯酚-氯仿萃取和乙醇沉淀之后,将基因组DNA重悬浮在水中,提供用于基因组测序。
为了全长Ad基因组测序,将纯化的病毒DNA雾化以产生随机剪切的片段。用E.coliDNA聚合酶和多核苷酸激酶的克列诺片段(klenow fragment)将DNA片段平端化。平端片段在低熔点琼脂糖凝胶上跑动以纯化大小范围在1-3kb的片段,并克隆到pUC19载体的SmaI位点以产生猎枪文库(shotgun library)。连接物用于转化感受态XL1-Blue MRF。通过在含X-gal和IPTG的LB琼脂上的白色/蓝色筛选鉴定阳性菌落。从文库中分离出质粒DNA的三到四个96孔板(block),用pUC正向和反向引物测序。使用Phred-Phrap软件包筛选所有测序读数的质量和载体序列。将通过了筛选的读数装配成邻接物(contigs)。设计引物来直接测序腺病毒DNA用于封闭缺口,并确定两个末端的DNA序列。
对选定的病毒获得了完整的病毒基因组序列,包括ChAd3(SEQ ID NO:1)、ChAd6(SEQ ID NO:2)、CV32(SEQ ID NO:3)、CV33(SEQ ID NO:4)和CV23(SEQ ID NO:5)。表1提供了数据,总结了ChAd3、ChAd6、Pan5(CV23)、Pan6(CV32)、Pan7(CV33)、C1和C68腺病毒基因组的核苷酸序列之间的同一性百分比。使用作为FASTA程序包版本2的部分的ALIGN程序计算比对(William R.Penson,University of Virginia;Myers&Miller,CABIOS 1989,4:11-17)。
表1.黑猩猩腺病毒基因组之间的核苷酸序列同一性百分比
为了表征新的腺病毒分离物(例如,ChAd20、ChAd4、ChAd5、ChAd7、ChAd8、ChAd9、ChAd10、ChAd11、ChAd16、ChAd17、ChAd19、ChAd22、ChAd24、ChAd26、ChAd30、ChAd31、ChAd37、ChAd38、ChAd44、ChAd63和ChAd82),也通过引物步进(primer walking)确定了六邻体和纤维基因的核苷酸序列。纤维基因:SEQ ID NO:6-15:(SEQ ID NO:6,ChAd20);(SEQ ID NO:7,ChAd4);SEQ ID NO:8,ChAd5);SEQ ID NO:9,ChAd7);SEQ ID NO:10,ChAd9);SEQ ID NO:11,ChAd10);SEQ ID NO:12,ChAd11);SEQ ID NO:13,ChAd16)SEQ ID NO:14,ChAd17),SEQID NO:15,ChAd19)和(SEQ ID NO:58,ChAd8),(SEQ ID NO:60,ChAd22),(SEQ ID NO:62,ChAd24),(SEQ ID NO:64,ChAd26),(SEQ ID NO:66,ChAd30),(SEQ IDNO:68,ChAd31),(SEQID NO:70,ChAd37),(SEQ ID NO:72,ChAd38),(SEQ ID NO:74,ChAd44),(SEQ ID NO:76,ChAd63)和(SEQ ID NO:78,ChAd82)。附图20A-20G提供了在此公开和要求权利的ChAd分离物的纤维蛋白的氨基酸序列的比较。
在以下列出了六邻体基因序列:SEQ ID NOS:16-25:(SEQ ID NO:16,ChAd20);SEQID NO:17,ChAd4);SEQ ID NO:18,ChAd5);SEQ ID NO:19,ChAd7);SEQ ID NO:20,ChAd9);SEQ ID NO:21,ChAd10);SEQ ID NO:22,ChAd11);SEQ ID NO:23,ChAd16);SEQ ID NO:24,ChAd17)SEQ ID NO:25,ChAd19),(SEQ ID NO:97,ChAd8),(SEQ ID NO:99,ChAd22),(SEQID NO:101,ChAd24),(SEQ ID NO:103,ChAd26),(SEQ ID NO:105,ChAd30),(SEQ ID NO:107,ChAd31),(SEQ ID NO:109,ChAd37),(SEQ ID NO:111,ChAd38),(SEQ ID NO:113,ChAd44),(SEQ ID NO:115,ChAd63)和(SEQ ID NO:117,ChAd82)。附图31A-31J提供了在此公开和要求权利的ChAd分离物的六邻体蛋白的氨基酸序列的比较。
黑猩猩腺病毒分类
根据已经建议的人类腺病毒血清型(分为六个亚群)的分类(Horowitz,MS(1990)Adenoviridae and their replication.In Virology B.N.Fields and D.M.Knipe,eds(Raven Ptess,New York)pp.1679-1740)将不同的黑猩猩腺病毒株分类,通过使用Align X程序(Informax,Inc)进行氨基酸和核苷酸序列比对来得出。
通过查看不同限制性内切酶的病毒基因组限制性图谱和通过分析六邻体基因的高变区7(HVR7)的序列,得到新的分离物的初步分类。为此,对侧翼于HVR7的高度保守区域设计两个引物,TGTCCTACCAR CTCTTGCTTGA(SEQ ID NO.45)和GTGGAARGGCACGTAGCG(SEQ IDNO.46)。使用纯化的病毒DNA或粗的293溶胞产物作为模板通过PCR扩增HVR7,然后测序。根据HVR7序列分析,我们将新分离的病毒分类入对人类腺病毒所提出的亚群(A-F)(Horowitz,MS(1990)Adenoviridae and their replication.In Virology B.N.Fieldsand D.M.Knipe,eds(raven Press,New York)pp.1679-1740)。
通过比对人类和黑猩猩腺病毒六邻体氨基酸序列获得附图35中呈现的系统树。该结果与根据使用Align X程序(Informax,Inc)限于六邻体HVR7的核苷酸序列比对的初步分类相一致。由采用PAUPSEARCH(Wisconsin Package Version 10.3,Accelrys Inc.)进行的全长六邻体肽序列的多重序列比对得出该树,并用TREEVIEW进行可视化和操作。使用Wisconsin程序包中安装的PAUPSEARCH程序进行Bootstrap置信度分析。对于每个比对,使用“Heuristic Search”作为检索条件和Maximum Parsimony作为最优条件将程序运行1000次重复,报告的置信度值取自50%majority-rule consensus。
实施例2:ChAd穿梭载体和表达载体的构建以及营救载体的构建和营救
使用适合的穿梭载体通过同源重组将基因组病毒DNA克隆到标准质粒载体中,所述穿梭载体含有来源于病毒基因组的左末端和右末端的病毒DNA序列(附图2)。如以下更完整地描述的,采用在分类为相同血清型亚群的病毒之间观察到的序列同源性来开发类群特异性穿梭载体。分类为D和E亚群的黑猩猩腺病毒的基因组病毒DNA结果是足够同源的,容许构建通用穿梭载体来克隆属于这两个亚群的病毒。
D/E亚群穿梭载体的构建
完全地测序了ChAd6病毒基因组(SEQ ID NO:2),获得的信息用于构建穿梭载体以便于通过D和E亚群黑猩猩腺病毒的同源重组来进行克隆。
在附图1中描述了构建ChAd6穿梭载体,在此称为pARS ChAd6-3。附图32提供了用于在此描述的克隆实验的寡核苷酸序列的列表(SEQ ID NO:26-40和SEQ ID NO:45-46)。简要地,通过用寡核苷酸5′-
ATGGAATTCGTTTAAACCATCATCAATAATATACCTC-3(SEQ ID NO:27)和5′-CGCTGGCACTCAAGAGTGGCCTC-3’(SEQ ID NO:28)通过PCR扩增来自ChAd6 DNA的左末端的457bp,用EcoRI和SnaBI消化并克隆入EcoRI-SnaBI酶切的pNEBAd35-2,产生pNEBChAd6-LI。通过使用寡核苷酸5’-ATGAAGCTTGTTTAAACCCATCATCAATAATATACCT-3’(SEQ ID NO:29)和5’-ATCTAGACAGCGTCCATAGCTTACCG-3’(SEQ ID NO:30)通过PCR扩增右侧ChAd6 ITR(bp36222到bp 36648),用限制性内切酶HindIII和XbaI消化并克隆入HindIII-XbaI消化的pNEBChAd6-LI,产生pNEBChAd6-RLI。最后,与ChAd6基因组DNA序列的核苷酸3426-3813相应的DNA片段用寡核苷酸:5′-
ATGCTACGTAGCGATCGCGTGAGTAGTGTTTGGGGGTGGGTGGG-3’(SEQ ID NO:31)和5′-TAGGCGCGCCGCTTCTCCTCGTTCAGGCTGGCG-3’(SEQ ID NO:32)扩增,用SnaBI和AscI消化,然后与SnaBI-AscI消化的pNEBChAd6-RLI连接,从而产生pNEBChAd6-RLIdE1。
为了改善在DH5α E.coli菌株中的重组和质粒增殖的效率,通过PmeI消化从pNEBChAd6-RLIdEl切下含有ChAd6的左侧和右侧ITR以及pIX基因片段的1306bp片段,并转移到不同的质粒载体,所述质粒载体通过用寡核苷酸:5′-
GATCTAGTTAGTTTAAACGAATTCGGATCTGCGACGCG-3’(SEQ ID NO:33)和5′TTCGATCATGTTTAAACGAAATTAAGAATTCGGATCC-3’(SEQ ID NO:34)通过PCR扩增从pMRKAd5SEAP获得。这个最终的连接步骤产生ChAd6穿梭载体pARSChAd6-3。
C亚群穿梭载体的构建
完全地测序了ChAd3病毒基因组(SEQ ID NO:1),获得的信息用于构建穿梭载体以便于通过C亚群黑猩猩腺病毒的同源重组来进行克隆。
简要地,用于克隆C亚群黑猩猩腺病毒的穿梭载体,在此称为pChAd3EGFP,如下构建:用寡核苷酸5′-
TATTCTGCGATCGCTGAGGTGGGTGAGTGGGCG-3’(SEQ ID NO:35)和5′-TAGGCGCGCCCTTAAACGGCATTTGTGGGAG-3’(SEQ ID NO:36)通过PCR扩增含有pIX编码区的ChAd3 DNA片段(nt 3542-4105),用SgfI-AscI消化,然后克隆到用SgfI-AscI消化的pARSCV32-3中,产生pARS-ChAd3D。用寡核苷酸5′-
CGTCTAGAAGACCCGAGTCTTACCAGT-3’(SEQ ID NO:37)和5′-
CGGGATCCGTTTAAACCATCATCAATAATATACCTTATT-3’(SEQ ID NO:38)通过PCR扩增ChAd3右末端(nt 37320-37441),用XbaI和BamHI消化,然后连接到用XbaI和BamHI限制的pARS-ChAd3D,产生pARS-ChAd3RD。用寡核苷酸5′-
ATGGAATTCGTTTAAACCATCATCAATAATATACCTT-3’(SEQ ID NO:39)和5′-
ATGACGCGATCGCTGATATCCTATAATAATAAAACGCAGACTTTG-3’,(SEQ ID NO:40)通过PCR扩增ChAd3病毒DNA左末端(nt 1-460),用EcoRI和SgfI消化,然后克隆到用EcoRI和SgfI消化的pARS-ChAd3RD,从而产生pARS-ChAd3RLD。还设计病毒DNA盒以含有位于两个ITR的末端的限制性内切酶位点(Pmel),从而消化将从质粒DNA释放病毒DNA。
B亚群穿梭载体的构建
根据已经描述的C和D/E亚群穿梭体构建的策略,构建B亚群穿梭体。简言之,通过用ChAd30的相应片段取代左侧末端、pIX区域、右侧末端来修饰pARS-ChAd3RLD。此外,用克隆在ChAd30 E4启动子的控制下的Ad5 E4orf6替代ChAd30的E4区域。该穿梭质粒命名为pChAd30 EGFP穿梭载体。
ΔE1黑猩猩腺病毒载体的构建
B亚群:通过在E.coli菌株BJ5183中进行同源重组来构建B亚群黑猩猩腺病毒载体。用BstEII和Bstl107I消化的pChAd30EGFP穿梭载体与ChAd8和ChAd30,纯化的病毒DNA,共转化BJ5183细胞。在pIX基因、存在于线性化pChAd30EGFP穿梭体和病毒基因组DNA末端的右侧ITR DNA序列之间的同源重组,容许它插入到质粒载体中,同时删除被EGFP表达盒替换的E1区域。构建根据人类细胞巨化病毒(HCMV)启动子和牛生长激素多聚腺苷酸信号(BghpolyA)的表达盒,来表达分泌的碱性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS区域(如附图3中对ChAd6穿梭载体所描述的)以及肿瘤相关抗原如来自人类和恒河猴来源的CEA和HER2/neu。所有表达盒都通过同源重组插入到ChAd30载体中。
C亚群:通过在E.coli菌株BJ5183中进行同源重组来构建C亚群黑猩猩腺病毒载体。用BstEII和Bstl107I消化的pChAd3EGFP穿梭载体与ChAd3、ChAd11、ChAd19和ChAd20纯化的病毒DNA共转化BJ5183细胞。在pIX基因、存在于线性化pChAd3EGFP和病毒基因组DNA末端的右侧ITR DNA序列之间的同源重组,容许它插入到质粒载体中,同时删除被EGFP表达盒替换的E1区域。构建根据人类细胞巨化病毒(HCMV)启动子和牛生长激素多聚腺苷酸信号(Bgh polyA)的表达盒,来表达分泌的碱性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS区域(如附图3中对ChAd6穿梭载体所描述的)以及肿瘤相关抗原如来自人类和恒河猴来源的CEA和HER2/neu。
D和E亚群:为了根据D和E亚群黑猩猩腺病毒构建ΔE1载体,用AscI消化穿梭载体pARS ChAd6-3,与CV32、CV33、CV68、ChAd4、ChAd5、ChAd6、ChAd7、ChAd9、ChAd10、和ChAd16纯化的病毒DNA共转染入E.coli菌株BJ5183。在来自pIX基因的DNA序列和存在于线性化pARSChAd6-3和病毒基因组DNA末端的右侧ITR DNA序列之间的同源重组,容许它插入到质粒载体中,同时删除E1区域(附图2和4)。
构建根据人类细胞巨化病毒(HCMV)启动子和牛生长激素多聚腺苷酸信号(BghpolyA)的表达盒,来表达分泌的碱性磷酸酶(SEAP)、EGFP、HIV gag、HCV NS基因(附图3)以及肿瘤相关抗原如人类和恒河猴来源的CEA和HER2/neu。所有的表达盒都插入到pARSChAd6-3载体的单个SnaBI位点,以通过同源重组转移到如附图4描述的ΔE1腺病毒前质粒中。
ΔE1载体的营救和扩增
种植在6cm细胞培养平皿上的5×106个PER.C6TM细胞用通过核酸内切酶消化从质粒序列释放的10微克克隆病毒载体转染。使用Lipofectamine(Invitrogen)进行DNA转染。转染后5-10天收集转染的细胞和培养基,通过冷冻和解冻裂解。然后通过在293或PER.C6TM细胞上连续传代来扩增营救的载体。通过感染种植在5-10个细胞工厂(NUNC,Inc.)上总共1-2×109个细胞来进行大规模的扩增。通过两次运行超速离心机,在氯化铯梯度上获得纯化的载体制品,相对含10%甘油的PBS进行透析,以等分量保存在-70℃。
实施例3:中和研究
为了评估针对在此公开的黑猩猩腺病毒的中和抗体在人类血清中的流行度,进行中和分析。该分析评估了血清预孵化对携带分泌碱性磷酸酶(SEAP)基因的黑猩猩腺病毒转导人类293细胞的能力的影响。中和滴度被定义为给出在有单独的病毒的阳性对照中观察到的SEAP活性的50%降低的血清稀释度。
将CV33-SEAP、CV32-SEAP和ChAd3-SEAP载体的2×106到1.5×107个物理粒子稀释在100μl完全培养基中,添加到稀释于完全培养基中的等体积的人类或黑猩猩血清中。在各种稀释度测试每种血清样品(从1/18稀释度开始的五个4倍的增加,到1:4608)。将样品在37℃预孵化一小时,然后添加到播种于96孔平板(3×104细胞/孔)中的293细胞。孵化一小时后除去接种物,用新鲜培养基重新喂养细胞,24小时后,移出50μl的培养基,通过化学发光分析测量SEAP活性。中和滴度被定义为给出在有单独的病毒的阳性对照中观察到的SEAP活性的50%降低的血清稀释度。测试一组100个人类血清的ChAd中和活性。并行的用Ad5 SEAP载体测试相同的组。
表2.针对黑猩猩腺病毒的中和抗体的流行度
表2中提供的结果表明了针对来源于黑猩猩腺病毒的载体的中和抗体在人类血清中的极低的流行度。仅四份血清显示了对于CV32载体的超过阈值200的滴度,而8份显示了对于ChAd3 SEAP载体的超过200的滴度。相反地,检查的黑猩猩血清的组显示了抗黑猩猩Ad免疫性的非常高的流行度。这些发现证实了如所预期的,基于黑猩猩Ad的载体具有非常小的机会在人类中被中和。因此它们是对先存的抗人类Ad免疫性难题的理想解决方案,所述免疫性限制了基于常见人类Ad血清型例如Ad5的病毒载体的施用。
实施例4:ChAd载体向性(tropism)
通过在不同组织来源的人类初级细胞的组上的EGFP表达,来评定Ad5和ChAd载体介导的基因转移效力。根据厂家的指示培养人类软骨细胞、成骨细胞、角质形成细胞、黑素细胞、骨骼肌细胞和黑素细胞。如所描述的获得人类单核细胞、不成熟的和成熟的树突状细胞(DC)(Romani,N.et al.1996,J.Immunol.Methods,196,137.)。通过FACS分析检测转导的荧光细胞。测试的人类初级细胞的组(panel)包括在心血管疾病、类风湿性关节炎、组织工程(骨骼、皮肤和软骨)和疫苗接种领域对基于体内以及体外基因转移的不同治疗策略很重要的靶细胞。附图38A-D中呈现的结果表明,如不同细胞类型感染的不同效率所展现的,不同的黑猩猩腺病毒可以识别除CAR以外的受体。
鼠免疫研究
方法和材料:
免疫方案和脾细胞/PBMC制备
免疫:用在0.1ml缓冲液中稀释的选定腺病毒免疫小鼠。每个载体剂量分成两个50μl的等分量,注射到小鼠的两个四头肌中。
脾细胞制备:注射后3周处死小鼠,切除它们的脾脏,转移到10ml R10中(10%FCS、55mM 2-巯基乙醇、1M HEPES缓冲液、2mM L-谷氨酰胺、RPMI培养基1640中的1X青霉素-链霉素溶液)。通过钢筛切碎脾脏,用2ml R10洗涤筛子之后,将脾细胞转移到50ml Falcon试管中,在室温(rt)以1200rpm离心10分钟。除去上清液,添加3ml ACK裂解缓冲液(Gibco BRLFormulation#79-0422DG)。室温下孵化细胞5分钟。添加45ml IX PBS,如上述对试管进行离心。用30ml R10洗涤之后,将细胞重悬浮在5ml R10中,通过70m尼龙细胞过滤器(Falcon2350)过滤。用990μl Turk′s溶液(Merck 040417345)稀释10μl的细胞,进行计数。最后将细胞稀释到R10中的107细胞/ml。
外周血单核细胞(PBMC)制备:将小鼠血液样品(150μl)转移到含50μl PBS/2%EDTA的2ml eppendorf试管。向每个试管添加1ml ACK缓冲液。轻轻地混合并在RT孵化5分钟。样品在微离心机中以1500rpm离心5分钟。弃去上清液,组合来自相同的免疫群(immunized cohorts)的白血球沉淀。重复ACK缓冲液孵化,然后将PBMC的沉淀重悬浮在1mlR10培养基中。
IFN-γ ELISPOT分析
用以2.5μg/ml的浓度在PBS中稀释的纯化的大鼠抗小鼠IFN-γ单克隆抗体(Pharmingen,cat.551216)以100μl/孔包被Millipore MAIP 45平板,在4℃孵化过夜(o/n)。用无菌的PBS洗涤平板两次,通过在CO2孵化器中与200μl/孔的R10孵化2小时来封闭非特异性结合位点。在表达HIV gag的Ad载体的免疫实验中,将9-mer的肽(AMQMLKETI,Balb/C小鼠中定位的CD8 HIV gag表位)(SEQ ID NO:47)在R10中稀释到2μg/ml,以50μl/孔的数量添加到孔中。在用HCV-NS表达载体进行的免疫实验中,使用了一肽库,其覆盖了NS3解旋酶结构域和代表解旋酶结构域中包含的定位的CD8表位的9-mer肽。通过覆盖完整氨基酸序列的重叠的15-mer肽的库,来评估表达人类CEA抗原的ChAds的免疫试验。作为对照使用DMSO和伴刀豆球蛋白A。以5×105和2.5×105的数量向每个孔中添加细胞。在CO2孵化器中o/n孵化之后,用0.05%Tween 20/PBS洗涤平板,添加在分析缓冲液(5%FBS、0.005%Tween20、PBS)中稀释1/250的50μl/孔的生物素化大鼠抗小鼠IFN-γ单克隆抗体(PharMingencat.554410)。在4℃孵化平板o/n,如上进行洗涤。在分析缓冲液中将链霉抗生物素蛋白-碱性磷酸酶结合物(BD554065)稀释1/2500,以50μl/孔的数量添加,室温2小时。洗涤之后,向平板添加50μl/孔的BCIP/NBT1-step溶液(Pierce 34042)进行显影。通过用去离子水洗涤孔停止反应。通过ELISPOT读数器自动地对斑点计数。
鼠IFN-γ细胞内染色(ICS)
将脾细胞稀释为2×106细胞每1ml R10,用如上所述相同的抗原以2μg/ml的浓度刺激。作为对照,使用DMSO和葡萄球菌肠毒素B(SEB)。在CO2孵化器中过夜孵化之后,用FACS缓冲液(1%FCS、0.01%NaN3、PBS)洗涤细胞,将纯化的抗小鼠CD16/CD32 Fc片段(克隆2.4G2,Pharmingen cat.553142)稀释1/25,以100μl/样品的数量添加,在4℃孵化15分钟。在FACS缓冲液中洗涤细胞,以100μl/样品的数量添加在FACS缓冲液中1∶50稀释的结合APC的抗小鼠CD3e(克隆145-2C11,Pharmingen#553066)、结合PE的抗小鼠CD4(克隆L3T4,BDPharmingen cat.553142)和结合PerCP的抗小鼠CD8a(克隆53-6.7,Pharmingencat.553036)。将细胞室温孵化30分钟,洗涤,固定并渗透化(permeabilized)(BectonDickinson,FACS Perm 2),与在PermWash(100μl/样品)中1∶50稀释的结合FITC的抗小鼠IFN-γ(Pharmingen cat.554411)在室温孵化30分钟。洗涤后的细胞重悬浮在500μl 1%甲醛/PBS中,使用CellQuest软件(Becton Dickinson)在FACS-Calibur流动细胞计数器上,进行细胞内细胞因子染色(ICS)分析。
实施例5:ChAd载体在小鼠中引发强烈的CMI反应
使用表达HIV gag转基因的载体在小鼠中评估在此公开的ChAd载体引发细胞介导的免疫反应(CMI)的能力。简要地,用从105直到1010vp/小鼠的成十倍增加剂量的不同载体注射5只Balb/C小鼠的各组。
注射后三周通过对脾细胞中gag特异性CD8+T细胞进行定量来确定免疫反应的强度。在体外用产生Balb/C小鼠中定位的gag CD8+T细胞表位的肽进行刺激之后,通过ELISPOT分析或通过IFN-γ细胞内染色和FACS分析来测定分泌INF-γ的CD8+T细胞的数量。
从5个免疫的动物获得结果,在表3中报告,表示为每106个脾细胞中的斑点形成细胞。显示的是,在与9-mer CD8+gag表位或与gag肽库孵化之后每百万个脾细胞的斑点形成细胞的数量。gag肽库由重叠10aa、涵盖完整的gag序列的20aa的肽组成。阳性值以粗体报告。
表3中提供的数据表明,施用在此公开和要求权利的ChAd载体引发了强烈的细胞介导的免疫反应,其是能够与hAd5引发的反应相比较的。通过察看引起阳性免疫结果的最低载体剂量(免疫断点),我们对不同载体的效力进行了评分,C亚群ChAd3gag是最有效的,断点在106pp载体剂量。免疫断点的评分在附图33中示出。
表3.用黑猩猩Ad载体免疫的Balbc小鼠中的gag特异性T细胞反应
实施例6:ChAd3和CV33 GAG载体引发以GAG特异性CD8+T细胞为特征的CMI反应
为了表征响应于包含HIV gag转基因的ChAd载体而引发的CMI反应,来自用不同剂量的载体免疫的五只小鼠的群组(cohorts)的脾细胞库通过细胞内IFN-γ染色进行分析。表3和表4中显示的数据是在独立的实验中采集的。
将脾细胞稀释为2×106细胞每1ml R10,用如上所述相同的抗原以2μg/ml的浓度刺激。作为对照,使用DMSO和SEB(葡萄球菌肠毒素B)。在CO2孵化器中o/n孵化之后,用FACS缓冲液(1%FCS、0.01%NaN3、PBS)洗涤细胞,将纯化的抗小鼠CD16/CD32 Fc片段(克隆2.4G2,Pharmingen cat.553142)稀释1/25,以100μl/样品的数量添加,在4℃孵化15分钟。在FACS缓冲液中洗涤细胞,以100μl/样品的数量添加在FACS缓冲液中1∶50稀释的结合APC的抗小鼠CD3e(克隆145-2C11,Pharmingen#553066)、结合PE的抗小鼠CD4(克隆L3T4,BDPharmingen cat.553142)和结合PerCP的抗小鼠CD8a(克隆53-6.7,Pharmingencat.553036)。将细胞室温孵化30分钟,洗涤,固定并渗透化(permeabilized)(BectonDickinson,FACS Perm 2),与在PermWash(100μl/样品)中1∶50稀释的结合FITC的抗小鼠IFN-γ(Pharmingen cat.554411)在室温孵化30分钟。洗涤后的细胞重悬浮在500μl 1%甲醛/PBS中,使用CellQuest软件(Becton Dickinson)在FACS-Calibur流动细胞计数器上进行分析。
表4提供了数据,总结了作为gag特异性CD8+或CD4+T细胞的gag特异性CD3+T细胞的百分比。阳性结果以粗体报告。在此提供的数据表明,由来源于分类为不同血清型亚群(即,C、D和E亚群)的病毒的ChAd载体引发的免疫反应的细胞分布型是类似的,所有gag特异性反应都主要以CD8+T细胞为特征。此外,注意到,在高的载体剂量下,在所有免疫实验中gag特异性CD4+反应都变得明显。ICS分析证实了ChAd3载体可以以106载体剂量刺激抗gagCD8+反应。
表4.用不同亚群的黑猩猩腺病毒载体免疫的小鼠中gag特异性T细胞的表征
实施例7:ChAd载体引发HCV NS特异性T细胞反应
相对于MRKAd6NSmut的效力,在C57/Black6小鼠中评估了CV32-NSmut和CV33-NSmut载体的效力。动物注射了从107开始直到109vp/小鼠的成10倍增加的载体剂量。单次注射后3周,通过用再生NS3蛋白的解旋酶结构域中定位的CD8+T细胞表位的9-mer肽刺激T细胞,通过IFN-γ ELISPOT和IFN-γ细胞内染色来分析CMI。表5中提供的数据总结了不存在(模拟的(mock))或存在NS3 9-mer肽的孵化之后每百万个脾细胞的斑点形成细胞的数目。
数据表明,表达HCV-NS的CV32和CV33载体都刺激强烈的T细胞反应。根据通过注射109vp/剂量获得的对CV32载体的第一个阳性结果的观察,CV32DE1E3 NSmut载体的免疫效力好像比人类C亚群Ad6DE1E3 NSmut载体低大约100倍。用MRKAd6NSmut的平行试验表明,107vp/动物的剂量足够刺激细胞介导的免疫。因此,这些结果证实了,在用表达gag的载体的实验中也观察到的(参见表3)、相对于人类C亚群载体(例如hAd5和hAd6),CV32衍生的载体的更低的免疫效力。
表5.在用Mrkad6 Nsmut、CV32NSmut或CV33NSmut免疫的小鼠中的HCV NS特异性T细胞反应
实施例8:抗Ad5的先存免疫性不取消ChAd3gag引发的抗gag CMI
为了评估针对高血清型流行度的Ad5的先存免疫性对ChAd3免疫的影响,在0和2周在四头肌中两次注射1010vp的Ad5wt来预先免疫各5只BalbC小鼠的4个群组。作为对照,各5只小鼠的两个群组在相同的时间点仅用缓冲液注射。然后用106和107vp/小鼠的Ad5gag或ChAd3gag载体免疫Ad5预免疫的小鼠的群组。用106和107vp/小鼠的Ad5gag或ChAd3gag载体免疫对照(幼稚)小鼠的群组。
在第4周通过如上所述的中和分析使用Ad5和ChAd3 SEAP载体评估抗Ad5和ChAd3中和免疫性。对用含有在BalbC小鼠中定位的gag表位的gag 9-mer肽刺激的纯化脾细胞进行ELISPOT分析来评估抗gag免疫性。在附图36中报告的结果证明,抗Ad5免疫性不取消ChAd3gag引发的抗gag CMI,而如所预料的,抗Ad5免疫性完全地阻断了Ad5gag免疫。
实施例9:ChAd3hCEA免疫在表达人类CEA的转基因小鼠中引发强烈的CEA特异性免疫反应
还在表达人类CEA的转基因小鼠(Clarke,P et al.Cancer Res.(1998)58(7):1469-77.)中评估了在此公开和要求权利的ChAd载体引发针对自体抗原的免疫反应从而破坏耐受性的能力。
用已经描述的1010vp ChAd3hCEA或Ad5hCEA在四头肌中注射各8只小鼠的群组。在用包含从aa 497到末端(aa 703)的人类CEA氨基酸序列的15-mer肽的库刺激的PBMC上,每周监视针对CEA的免疫反应,直到第75天。通过ICS确定响应于CEA肽库孵化的分泌干扰素-γ的CD4-CD8+T细胞,来评估抗CEA免疫性。
在附图37中报告的结果表明,与表达相同转基因的Ad5相比,ChAd3hCEA载体免疫刺激了针对人类CEA的更加持久的CD8+T细胞反应。
灵长类免疫研究
方法和材料:
免疫方案
还评估了在此公开和要求权利的ChAd载体在恒河猴(在此称为猴)中引发CMI的能力。麻痹恒河猴(开他敏/甲苯噻嗪),使用结核菌素注射器(Becton-Dickinson)以0.5mL等分量向两个三角肌中肌肉内递送疫苗。在所有情况中,恒河猴体重在3-10公斤之间,在1mL缓冲液中施用每个疫苗的总剂量。
从在免疫期间的几个时间点收集的血液样品制备血清和外周血单核细胞(PBMC)。所有动物照料和处理都根据动物照料和使用委员会机构(Institutional Animal Careand Use Committee)提供的标准,根据Guide for Care and Use of LaboratoryAnimals,Institute of Laboratory Animal Resources,National Research Council中阐述的原则进行。
ELISPOT分析
根据早先描述的方案(Allen et al.,2001 J.Virol.75(2):738-749)进行对恒河猴的IFN-γ ELISPOT分析,有某些修改。对于gag特异性刺激,从涵盖完整HIV-1 gag序列具有10-aa重叠的20-aa的肽制备肽库(Synpep Corp.,Dublin,CA)。对于HCV NS特异性刺激,从涵盖NS3到NS5b的完整HCV-NS序列的具有10-aa重叠的15-aa肽制备6个肽库。
用涵盖完整蛋白序列的具有10-aa重叠的15-aa肽进行HER2/neu和CEA特异性刺激。
向每个加样孔添加50μL 2-4×105个外周血单核细胞(PBMC);使用BeckmanCoulter Z2粒子分析仪以设置在80fL的较低的尺寸截止(cut-off)对细胞进行计数。将50μL培养基或每种肽的浓度为8μg/mL的gag肽库添加到PBMC。样品在37℃,5%CO2孵化20-24小时。相应地发展出斑点,用根据ImagePro平台(Silver Spring,MD)定制的成像仪和自动计数子程序处理平板;将计数值标准化为106个细胞输入。
细胞内细胞因子染色(ICS)
向1ml的2×106PBMC/mL完全RPMI培养基(17×100mm圆底聚丙烯试管(Sarstedt,Newton,NC))中,添加抗hCD28(克隆L293,Becton-Dickinson)和抗hCD49d(克隆L25,Becton-Dickinson)单克隆抗体到1μg/mL的终浓度。对于gag特异性刺激,添加10μL的肽库(每种肽0.4mg/mL)。对HCV NS特异性刺激使用类似的条件。在37℃孵化试管1小时,之后添加20μL的5mg/mL布雷菲德菌素A(brefeldin A)(Sigma)。在37℃、5%CO2、90%湿度孵化细胞16小时。向每个试管添加4mL PBS/2%FBS,在1200rmp 10分钟将细胞团粒化。将细胞重悬浮在PBS/2%FBS中,使用几种荧光标记的mAbs对表面标记进行染色(30分钟,4℃):每试管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)。这个阶段的样品处理在黑暗中进行。洗涤细胞,在750μL 1×FACS Perm缓冲液(BectonDickinson)中在室温下孵化10分钟。将细胞团粒化,重悬浮在PBS/2%FBS中,添加0.1μgFITC-抗hIFN-γ,克隆MD-1(Biosource)。孵化30分钟后,洗涤细胞并重悬浮在PBS中。使用Becton Dickinson FACSCalibur仪器的所有四个彩色通道对样品进行分析。为了分析数据,首先除去(gated)低的侧向和前向分散的淋巴细胞群体;将用于细胞因子阳性事件的常用的荧光截止用于CD4+和CD8+群体,并用于样品的模拟和gag肽反应试管。
实施例10:在猴中使用ChAd ΔE1-gag载体的同源激发一强化方式引发Gag特异性T细胞
在第0周和第4周给予各3只动物的群组肌肉注射任何一种以下构建体:1010vp的CV-32ΔE1-gag;或1010vp CV33ΔE1-gag;或1010vp和108vp的MRKAd5ΔE1gag。以规律的4周间隔收集的PBMC在ELISPOT分析中进行分析。结果在表6中提供,其表明不存在(模拟)或存在Gag肽库的情况下孵化之后每百万个PBMC中斑点形成细胞的数目,确定了CV32ΔE1gag和CV33ΔE1gag能够在非人灵长类中诱导显著水平的gag特异性T细胞。有趣的是注意到,在单次剂量之后(第4周),CV32ΔE1-gag反应与MRKAd5 ΔE1-gag 108vp剂量相当,比MRKAd5-gag 1010vp/剂的更低。CV33ΔE1-gag 1010vp/剂诱导了与MRKAd5-gag 1010vp/剂的反应相当的反应。在第8周第二剂之后证实了这个结果。
表6.用Mrkad5ΔE1-Gag、CV32ΔE1-Gag、CV33ΔE1-Gag免疫的猴中的Gag特异性T细胞反应
实施例11:在异源的激发一强化方案中ChAd载体引发HCV NS特异性T细胞反应
在独立的实验中,在第0、4周以108或1010vp每只动物向两只和三只猴的组给予MRKAd6NSoptmut载体的免疫接种。在第24周以相同的剂量用相同的病毒对动物进行强化,在第104周以1010vp每只动物用CV33-NSmut再次强化。结果在表7和8中呈现,其总结了不存在(模拟的)或存在HCV NS肽库的孵化之后每百万个PBMC的斑点形成细胞的数目。
在第一剂之后第4周在注射了1010vp的动物中(表8),和在第8周(第2剂以后)在注射了108的动物中(表7),通过IFN-γ ELISPOT评定的T细胞免疫性显示了峰值反应。第24周的注射没有使反应强化(“同源强化”)而在注射CV33-NSmut之后观察到强烈的强化效果(“异源强化”)。
表7.用108vp/动物的MRK Ad6NSoptmut免疫和用CV33-Nsmut强化的猴中的HCV NS特异性T细胞反应
表8.用1010vp/动物的MRK Ad6NSoptmut免疫和用CV33-Nsmut强化的猴中的HCV NS特异性T细胞反应
在第二实验中评估用黑猩猩Ad载体异源强化的效率。在第0周和第4周用MRKAd5gag(1010vp/动物)、MRKAd6NSmut(1010vp/动物)或用两种载体的组合(每个载体1010vp/动物)免疫各三只猴的群组,然后在第24周用相同的免疫原强化(同源强化)。用相同的免疫原进行同源强化;用CV33gag、CV32 NSmut或用组合的这两种载体进行异源强化。表9中提供的结果总结了不存在(模拟的)或存在HCV NS肽库的孵化之后每百万个PBMC的斑点形成细胞的数目。
在第51周用CV33gag(1010vp/动物)、CV32NSmut(1010vp/动物)和用两种载体的组合(每种载体1010vp/动物)再次强化相同的群组。在表9中提供的结果进一步表明,由于反应低于注射第一剂疫苗后第4周观察到的峰值,同源强化不是很有效。在用异源黑猩猩载体免疫接种后在第54周通过IFN-γ ELISPOT测量到强烈的强化效果。
表9.在用MRK Ad5gag或MRK Ad6NSoptmut以1010vp/动物免疫的猴中,黑猩猩Ad载体的免疫接种有效地强化Gag和HCV NS特异性T细胞反应
实施例12:用包含TAA的ChAd载体进行疫苗接种在猴中破坏耐受性并引发TAA特异性T细胞反应
在各四只猴的群组中进行实验,所述实验被设计来确定黑猩猩腺病毒载体是否有足够的免疫原性来破坏对自体抗原的耐受性,并记录黑猩猩载体用于强化人类腺病毒载体激发的免疫反应的实用性。在第0、2和4周用包含肿瘤相关抗原CEA的Ad5DE1 RhCEA(1011vp)三次注射免疫动物,随后在第16、18和20周用CV33DE1 RhCEA(1011vp)接种。用恒河猴CEA肽通过IFN-γ ELISPOT测量T细胞反应。
结果在附图34中报告,其提供了在不存在(DMSO)或存在恒河猴CEA C和D肽库的孵化之后每百万PBMC中斑点形成细胞的数目,确定了基于用两种不同的Ad血清型的接种的免疫方案在非人灵长类中引起针对CEA的持续的T细胞反应。
虽然已经参考本发明的某些优选的实施方式详细描述了本发明,要理解的是,修改和变化都处在所描述的和要求权利的精神和范围之内。
序列表
<110> Merck & Co., Inc.
Instituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.
<120> 黑猩猩腺病毒疫苗载运体
<130> ITR0048Y PCT
<150> 60/538,799
<151> 2004-01-23
<160> 125
<170> FastSEQ for Windows Version 4.0
<210> 1
<211> 37741
<212> DNA
<213> 黑猩猩腺病毒-ChAd3基因组
<400> 1
catcatcaat aatatacctt attttggatt gaagccaata tgataatgag atgggcggcg 60
cgaggcgggg cgcggggcgg gaggcgggtt tgggggcggg ccggcgggcg gggcggtgtg 120
gcggaagtgg actttgtaag tgtggcggat gtgacttgct agtgccgggc gcggtaaaag 180
tgacgttttc cgtgcgcgac aacgcccccg ggaagtgaca tttttcccgc ggtttttacc 240
ggatgttgta gtgaatttgg gcgtaaccaa gtaagatttg gccattttcg cgggaaaact 300
gaaacgggga agtgaaatct gattaatttt gcgttagtca taccgcgtaa tatttgtcta 360
gggccgaggg actttggccg attacgtgga ggactcgccc aggtgttttt tgaggtgaat 420
ttccgcgttc cgggtcaaag tctccgtttt attattatag tcagctgacg cggagtgtat 480
ttataccctc tgatctcgtc aagaggccac tcttgagtgc cagcgagtag agttttctcc 540
tctgccgctc tccgctccgc tccgctcggc tctgacaccg gggaaaaaat gagacatttc 600
acctacgatg gcggtgtgct caccggccag ctggctgctg aggtcctgga caccctgatc 660
gaggaggtat tggccgataa ttatcctccc tcgactcctt ttgagccacc tacacttcac 720
gaactatacg atctggatgt ggtggggccc agcgatccga acgagcaggc ggtttccagt 780
ttttttccag agtccatgtt gttggccagc caggaggggg tcgaacttga gacccctcct 840
ccgatcgtgg attcccccga tccgccgcag ctgactaggc agcccgagcg ctgtgcggga 900
cctgagacta tgccccagct gctacctgag gtgatcgatc tcacctgtaa tgagtctggt 960
tttccaccca gcgaggatga ggacgaagag ggtgagcagt ttgtgttaga ttctgtggaa 1020
caacccgggc gaggatgcag gtcttgtcaa tatcaccgga aaaacacagg agactcccag 1080
attatgtgtt ctctgtgtta tatgaagatg acctgtatgt ttatttacag taagtttatc 1140
atcggtgggc aggtgggcta tagtgtgggt ggtggtcttt ggggggtttt ttaatatatg 1200
tcaggggtta tgctgaagac ttttttattg tgatttttaa aggtccagtg tctgagcccg 1260
agcaagaacc tgaaccggag cctgagcctt ctcgccccag gagaaagcct gtaatcttaa 1320
ctagacccag cgcaccggta gcgagaggcc tcagcagcgc ggagaccacc gactccggtg 1380
cttcctcatc acccccggag attcaccccc tggtgcccct atgtcccgtt aagcccgttg 1440
ccgtgagagt cagtgggcgg cggtctgctg tggagtgcat tgaggacttg ctttttgatt 1500
cacaggaacc tttggacttg agcttgaaac gccccaggca ttaaacctgg tcacctggac 1560
tgaatgagtt gacgcctatg tttgcttttg aatgacttaa tgtgtataga taataaagag 1620
tgagataatg ttttaattgc atggtgtgtt taacttgggc ggagtctgct gggtatataa 1680
gcttccctgg gctaaacttg gttacacttg acctcatgga ggcctgggag tgtttggaga 1740
actttgccgg agttcgtgcc ttgctggacg agagctctaa caatacctct tggtggtgga 1800
ggtatttgtg gggctctccc cagggcaagt tagtttgtag aatcaaggag gattacaagt 1860
gggaatttga agagcttttg aaatcctgtg gtgagctatt ggattctttg aatctaggcc 1920
accaggctct cttccaggag aaggtcatca ggactttgga tttttccaca ccggggcgca 1980
ttgcagccgc ggttgctttt ctagcttttt tgaaggatag atggagcgaa gagacccact 2040
tgagttcggg ctacgtcctg gattttctgg ccatgcaact gtggagagca tggatcagac 2100
acaagaacag gctgcaactg ttgtcttccg tccgcccgtt gctgattccg gcggaggagc 2160
aacaggccgg gtcagaggac cgggcccgtc gggatccgga ggagagggca ccgaggccgg 2220
gcgagaggag cgcgctgaac ctgggaaccg ggctgagcgg ccatccacat cgggagtgaa 2280
tgtcgggcag gtggtggatc tttttccaga actgcggcgg attttgacta ttagggagga 2340
tgggcaattt gttaagggtc ttaagaggga gaggggggct tctgagcata acgaggaggc 2400
cagtaattta gcttttagct tgatgaccag acaccgtcca gagtgcatca cttttcagca 2460
gattaaggac aattgtgcca atgagttgga tctgttgggt cagaagtata gcatagagca 2520
gctgaccact tactggctgc agccgggtga tgatctggag gaagctatta gggtgtatgc 2580
taaggtggcc ctgcggcccg attgcaagta caagctcaag gggctggtga atatcaggaa 2640
ttgttgctac atttctggca acggggcgga ggtggagata gagaccgaag acagggtggc 2700
tttcagatgc agcatgatga atatgtggcc gggggtgctg ggcatggacg gggtggtgat 2760
tatgaatgtg aggttcacgg ggcccaactt taacggcacg gtgtttttgg ggaacaccaa 2820
cctggtcctg cacggggtga gcttctatgg gtttaacaac acctgtgtgg aggcctggac 2880
cgatgtgaag gtccgcggtt gcgcctttta tggatgttgg aaggccatag tgagccgccc 2940
taagagcagg agttccatta agaaatgctt gtttgagagg tgcaccttgg ggatcctggc 3000
cgagggcaac tgcagggtgc gccacaatgt ggcctccgag tgcggttgct tcatgctagt 3060
caagagcgtg gcggtaatca agcataatat ggtgtgcggc aacagcgagg acaaggcctc 3120
acagatgctg acctgcacgg atggcaactg ccacttgctg aagaccatcc atgtaaccag 3180
ccacagccgg aaggcctggc ccgtgttcga gcacaacttg ctgacccgct gctccttgca 3240
tctgggcaac aggcgggggg tgttcctgcc ctatcaatgc aactttagtc acaccaagat 3300
cttgctagag cccgagagca tgtccaaggt gaacttgaac ggggtgtttg acatgaccat 3360
gaagatctgg aaggtgctga ggtacgacga gaccaggtcc cggtgcagac cctgcgagtg 3420
cgggggcaag catatgagga accagcccgt gatgctggat gtgaccgagg agctgaggac 3480
agaccacttg gttctggcct gcaccagggc cgagtttggt tctagcgatg aagacacaga 3540
ttgaggtggg tgagtgggcg tggcctgggg tggtcatgaa aatatataag ttgggggtct 3600
tagggtctct ttatttgtgt tgcagagacc gccggagcca tgagcgggag cagcagcagc 3660
agcagtagca gcagcgcctt ggatggcagc atcgtgagcc cttatttgac gacgcggatg 3720
ccccactggg ccggggtgcg tcagaatgtg atgggctcca gcatcgacgg ccgacccgtc 3780
ctgcccgcaa attccgccac gctgacctat gcgaccgtcg cggggacgcc gttggacgcc 3840
accgccgccg ccgccgccac cgcagccgcc tcggccgtgc gcagcctggc cacggacttt 3900
gcattcctgg gaccactggc gacaggggct acttctcggg ccgctgctgc cgccgttcgc 3960
gatgacaagc tgaccgccct gctggcgcag ttggatgcgc ttactcggga actgggtgac 4020
ctttctcagc aggtcatggc cctgcgccag caggtctcct ccctgcaagc tggcgggaat 4080
gcttctccca caaatgccgt ttaagataaa taaaaccaga ctctgtttgg attaaagaaa 4140
agtagcaagt gcattgctct ctttatttca taattttccg cgcgcgatag gccctagacc 4200
agcgttctcg gtcgttgagg gtgcggtgta tcttctccag gacgtggtag aggtggctct 4260
ggacgttgag atacatgggc atgagcccgt cccgggggtg gaggtagcac cactgcagag 4320
cttcatgctc cggggtggtg ttgtagatga tccagtcgta gcaggagcgc tgggcatggt 4380
gcctaaaaat gtccttcagc agcaggccga tggccagggg gaggcccttg gtgtaagtgt 4440
ttacaaaacg gttaagttgg gaagggtgca ttcggggaga gatgatgtgc atcttggact 4500
gtatttttag attggcgatg tttccgccca gatcccttct gggattcatg ttgtgcagga 4560
ccaccagtac agtgtatccg gtgcacttgg ggaatttgtc atgcagctta gagggaaaag 4620
cgtggaagaa cttggagacg cccttgtggc ctcccagatt ttccatgcat tcgtccatga 4680
tgatggcaat gggcccgcgg gaggcagctt gggcaaagat atttctgggg tcgctgacgt 4740
cgtagttgtg ttccagggtg aggtcgtcat aggccatttt tacaaagcgc gggcggaggg 4800
tgcccgactg ggggatgatg gtcccctctg gccctggggc gtagttgccc tcgcagatct 4860
gcatttccca ggccttaatc tcggaggggg gaatcatatc cacctgcggg gcgatgaaga 4920
aaacggtttc cggagccggg gagattaact gggatgagag caggtttcta agcagctgtg 4980
attttccaca accggtgggc ccataaataa cacctataac cggttgcagc tggtagttta 5040
gagagctgca gctgccgtcg tcccggagga ggggggccac ctcgttgagc atgtccctga 5100
cgcgcatgtt ctccccgacc agatccgcca gaaggcgctc gccgcccagg gacagcagct 5160
cttgcaagga agcaaagttt ttcagcggct tgaggccgtc cgccgtgggc atgtttttca 5220
gggtctggct cagcagctcc aggcggtccc agagctcggt gacgtgctct acggcatctc 5280
tatccagcat atctcctcgt ttcgcgggtt ggggcgactt tcgctgtagg gcaccaagcg 5340
gtggtcgtcc agcggggcca aagtcatgtc cttccatggg cgcagggtcc tcgtcagggt 5400
ggtctgggtc acggtgaagg ggtgcgctcc gggctgagcg cttgccaagg tgcgcttgag 5460
gctggttctg ctggtgctga agcgctgccg gtcttcgccc tgcgcgtcgg ccaggtagca 5520
tttgaccatg gtgtcatagt ccagcccctc cgcggcgtgt cccttggcgc gcagcttgcc 5580
cttggaggtg gcgccgcacg aggggcagag caggctcttg agcgcgtaga gcttgggggc 5640
gaggaagacc gattcggggg agtaggcgtc cgcgccgcag accccgcaca cggtctcgca 5700
ctccaccagc caggtgagct cggggcgcgc cgggtcaaaa accaggtttc ccccatgctt 5760
tttgatgcgt ttcttacctc gggtctccat gaggtggtgt ccccgctcgg tgacgaagag 5820
gctgtccgtg tctccgtaga ccgacttgag gggtcttttc tccagggggg tccctcggtc 5880
ttcctcgtag aggaactcgg accactctga gacgaaggcc cgcgtccagg ccaggacgaa 5940
ggaggctatg tgggaggggt agcggtcgtt gtccactagg gggtccacct tctccaaggt 6000
gtgaagacac atgtcgcctt cctcggcgtc caggaaggtg attggcttgt aggtgtaggc 6060
cacgtgaccg ggggttcctg acgggggggt ataaaagggg gtgggggcgc gctcgtcgtc 6120
actctcttcc gcatcgctgt ctgcgagggc cagctgctgg ggtgagtatt ccctctcgaa 6180
ggcgggcatg acctccgcgc tgaggttgtc agtttccaaa aacgaggagg atttgatgtt 6240
cacctgtccc gaggtgatac ctttgagggt acccgcgtcc atctggtcag aaaacacgat 6300
ctttttattg tccagcttgg tggcgaacga cccgtagagg gcgttggaga gcagcttggc 6360
gatggagcgc agggtctggt tcttgtccct gtcggcgcgc tccttggccg cgatgttgag 6420
ctgcacgtac tcgcgcgcga cgcagcgcca ctcggggaag acggtggtgc gctcgtcggg 6480
caccaggcgc acgcgccagc cgcggttgtg cagggtgacc aggtccacgc tggtggcgac 6540
ctcgccgcgc aggcgctcgt tggtccagca gagacggccg cccttgcgcg agcagaaggg 6600
gggcaggggg tcgagctggg tctcgtccgg ggggtccgcg tccacggtga aaaccccggg 6660
gcgcaggcgc gcgtcgaagt agtctatctt gcaaccttgc atgtccagcg cctgctgcca 6720
gtcgcgggcg gcgagcgcgc gctcgtaggg gttgagcggc gggccccagg gcatggggtg 6780
ggtgagtgcg gaggcgtaca tgccgcagat gtcatagacg tagaggggct cccgcaggac 6840
cccgatgtag gtggggtagc agcggccgcc gcggatgctg gcgcgcacgt agtcatacag 6900
ctcgtgcgag ggggcgagga ggtcggggcc caggttggtg cgggcggggc gctccgcgcg 6960
gaagacgatc tgcctgaaga tggcatgcga gttggaagag atggtggggc gctggaagac 7020
gttgaagctg gcgtcctgca ggccgacggc gtcgcgcacg aaggaggcgt aggagtcgcg 7080
cagcttgtgt accagctcgg cggtgacctg cacgtcgagc gcgcagtagt cgagggtctc 7140
gcggatgatg tcatatttag cctgcccctt ctttttccac agctcgcggt tgaggacaaa 7200
ctcttcgcgg tctttccagt actcttggat cgggaaaccg tccggttccg aacggtaaga 7260
gcctagcatg tagaactggt tgacggcctg gtaggcgcag cagcccttct ccacggggag 7320
ggcgtaggcc tgcgcggcct tgcggagcga ggtgtgggtc agggcgaagg tgtccctgac 7380
catgactttg aggtactggt gcttgaagtc ggagtcgtcg cagccgcccc gctcccagag 7440
cgagaagtcg gtgcgcttct tggagcgggg gttgggcaga gcgaaggtga catcgttgaa 7500
gaggattttg cccgcgcggg gcatgaagtt gcgggtgatg cggaagggcc ccggcacttc 7560
agagcggttg ttgatgacct gggcggcgag cacgatctcg tcgaagccgt tgatgttgtg 7620
gcccacgatg tagagttcca ggaagcgggg ccggcccttt acggtgggca gcttctttag 7680
ctcttcgtag gtgagctcct cgggcgaggc gaggccgtgc tcggccaggg cccagtccgc 7740
gaggtgcggg ttgtctctga ggaaggactc ccagaggtcg cgggccagga gggtctgcag 7800
gcggtccctg aaggtcctga actggcggcc cacggccatt ttttcggggg tgatgcagta 7860
gaaggtgagg gggtcttgct gccagcggtc ccagtcgagc tgcagggcga ggtcgcgcgc 7920
ggcggtgacc aggcgctcgt cgcccccgaa tttcatgacc agcatgaagg gcacgagctg 7980
ctttccgaag gcccccatcc aagtgtaggt ctctacatcg taggtgacaa agaggcgctc 8040
cgtgcgagga tgcgagccga tcgggaagaa ctggatctcc cgccaccagt tggaggagtg 8100
gctgttgatg tggtggaagt agaagtcccg tcgccgggcc gaacactcgt gctggctttt 8160
gtaaaagcga gcgcagtact ggcagcgctg cacgggctgt acctcctgca cgagatgcac 8220
ctttcgcccg cgcacgagga agccgagggg aaatctgagc cccccgcctg gctcgcggca 8280
tggctggtgc tcttctactt tggatgcgtg tccgtctccg tctggctcct cgaggggtgt 8340
tacggtggag cggaccacca cgccgcgcga gccgcaggtc cagatatcgg cgcgcggcgg 8400
tcggagtttg atgacgacat cgcgcagctg ggagctgtcc atggtctgga gctcccgcgg 8460
cggcggcagg tcagccggga gttcttgcag gttcacctcg cagagtcggg ccagggcgcg 8520
gggcaggtct aggtggtacc tgatctctag gggcgtgttg gtggcggcgt cgatggcttg 8580
caggagcccg catccccggg gggcgacgac ggtgccccgc ggggtggtgg tggtggtggt 8640
ggtggtggtg gtggcggtgc agctcagaag cggtgccgcg ggcgggcccc cggaggtagg 8700
gggggctccg gtcccgccgg caggggcggc agcggcacgt cggcgtggag cgcgggcagg 8760
agttggtgct gtgcccggag gttgctggcg aaggcgacga cgcggcggtt gatctcctgg 8820
atctggcgcc tctgcgtgaa gacgacgggc ccggtgagct tgaacctgaa agagagttcg 8880
acagaatcaa tctcggtgtc attgaccgcg gcctggcgca ggatctcctg cacgtctccc 8940
gagttgtctt ggtaggcgat ctcggccatg aactgctcga tctcttcctc ctggaggtct 9000
ccgcgtccgg cgcgttccac ggtggccgcc aggtcgttgg agatgcgccc catgagctgc 9060
gagaaggcgt tgagtccgcc ctcgttccag actcggctgt agaccacgcc cccctggtca 9120
tcgcgggcgc gcatgaccac ctgcgcgagg ttgagctcca cgtgccgcgc gaagacggcg 9180
tagttgcgca gacgctggaa gaggtagttg agggtggtgg cggtgtgctc ggccacgaag 9240
aagttcatga cccagcggcg caacgtggat tcgttgatgt cccccaaggc ctccagccgt 9300
tccatggcct cgtagaagtc cacggcgaag ttgaaaaact gggagttgcg cgccgacacg 9360
gtcaactcct cctccagaag acggatgagc tcggcgacgg tgtcgcgcac ctcgcgctcg 9420
aaggctatgg ggatctcttc ctccgctagc atcaccacct cctcctcttc ctcctcttct 9480
ggcacttcca tgatggcttc ctcctcttcg gggggcggcg gcggcggcgg tgggggaggg 9540
ggcgctctgc gccggcggcg gcgcaccggg aggcggtcca cgaagcgcgc gatcatctcc 9600
ccgcggcggc ggcgcatggt ctcggtgacg gcgcggccgt tctcccgggg gcgcagttgg 9660
aagacgccgc cggacatctg gtgctggggc gggtggccgt gaggcagcga aacggcgctg 9720
acgatgcatc tcaacaattg ctgcgtaggt acgccgccga gggacctgag ggagtccata 9780
tccaccggat ccgaaaacct ttcgaggaag gcgtctaacc agtcgcagtc gcaaggtagg 9840
ctgagcaccg tggcgggcgg cggggggtgg ggggagtgtc tggcggaggt gctgctgatg 9900
atgtaattga agtaggcgga cttgacacgg cggatggtcg acaggagcac catgtccttg 9960
ggtccggcct gctggatgcg gaggcggtcg gctatgcccc aggcttcgtt ctggcatcgg 10020
cgcaggtcct tgtagtagtc ttgcatgagc ctttccaccg gcacctcttc tccttcctct 10080
tctgcttctt ccatgtctgc ttcggccctg gggcggcgcc gcgcccccct gccccccatg 10140
cgcgtgaccc cgaaccccct gagcggttgg agcagggcca ggtcggcgac gacgcgctcg 10200
gccaggatgg cctgctgcac ctgcgtgagg gtggtttgga agtcatccaa gtccacgaag 10260
cggtggtagg cgcccgtgtt gatggtgtag gtgcagttgg ccatgacgga ccagttgacg 10320
gtctggtggc ccggttgcga catctcggtg tacctgagtc gcgagtaggc gcgggagtcg 10380
aagacgtagt cgttgcaagt ccgcaccagg tactggtagc ccaccaggaa gtgcggcggc 10440
ggctggcggt agaggggcca gcgcagggtg gcgggggctc cgggggccag gtcttccagc 10500
atgaggcggt ggtaggcgta gatgtacctg gacatccagg tgatacccgc ggcggtggtg 10560
gaggcgcgcg ggaagtcgcg cacccggttc cagatgttgc gcaggggcag aaagtgctcc 10620
atggtaggcg tgctctgtcc agtcagacgc gcgcagtcgt tgatactcta gaccagggaa 10680
aacgaaagcc ggtcagcggg cactcttccg tggtctggtg aatagatcgc aagggtatca 10740
tggcggaggg cctcggttcg agccccgggt ccgggccgga cggtccgcca tgatccacgc 10800
ggttaccgcc cgcgtgtcga acccaggtgt gcgacgtcag acaacggtgg agtgttcctt 10860
ttggcgtttt tctggccggg cgccggcgtc gcgtaagaga ctaagccgcg aaagcgaaag 10920
cagtaagtgg ctcgctcccc gtagccggag ggatccttgc taagggttgc gttgcggcga 10980
accccggttc gaatcccgta ctcgggccgg ccggacccgc ggctaaggtg ttggattggc 11040
ctccccctcg tataaagacc ccgcttgcgg attgactccg gacacgggga cgagcccctt 11100
ttatttttgc tttccccaga tgcatccggt gctgcggcag atgcgccccc cgccccagca 11160
gcagcaacaa caccagcaag agcggcagca acagcagcgg gagtcatgca gggccccctc 11220
acccaccctc ggcgggccgg ccacctcggc gtccgcggcc gtgtctggcg cctgcggcgg 11280
cggcgggggg ccggctgacg accccgagga gcccccgcgg cgcagggcca gacactacct 11340
ggacctggag gagggcgagg gcctggcgcg gctgggggcg ccgtctcccg agcgccaccc 11400
gcgggtgcag ctgaagcgcg actcgcgcga ggcgtacgtg cctcggcaga acctgttcag 11460
ggaccgcgcg ggcgaggagc ccgaggagat gcgggacagg aggttcagcg cagggcggga 11520
gctgcggcag gggctgaacc gcgagcggct gctgcgcgag gaggactttg agcccgacgc 11580
gcggacgggg atcagccccg cgcgcgcgca cgtggcggcc gccgacctgg tgacggcgta 11640
cgagcagacg gtgaaccagg agatcaactt ccaaaagagt ttcaacaacc acgtgcgcac 11700
gctggtggcg cgcgaggagg tgaccatcgg gctgatgcac ctgtgggact ttgtaagcgc 11760
gctggtgcag aaccccaaca gcaagcctct gacggcgcag ctgttcctga tagtgcagca 11820
cagcagggac aacgaggcgt ttagggacgc gctgctgaac atcaccgagc ccgagggtcg 11880
gtggctgctg gacctgatta acatcctgca gagcatagtg gtgcaggagc gcagcctgag 11940
cctggccgac aaggtggcgg ccatcaacta ctcgatgctg agcctgggca agttttacgc 12000
gcgcaagatc taccagacgc cgtacgtgcc catagacaag gaggtgaaga tcgacggttt 12060
ttacatgcgc atggcgctga aggtgctcac cctgagcgac gacctgggcg tgtaccgcaa 12120
cgagcgcatc cacaaggccg tgagcgtgag ccggcggcgc gagctgagcg accgcgagct 12180
gatgcacagc ctgcagcggg cgctggcggg cgccggcagc ggcgacaggg aggcggagtc 12240
ctacttcgat gcgggggcgg acctgcgctg ggcgcccagc cggcgggccc tggaggccgc 12300
gggggtccgc gaggactatg acgaggacgg cgaggaggat gaggagtacg agctagagga 12360
gggcgagtac ctggactaaa ccgcgggtgg tgtttccggt agatgcaaga cccgaacgtg 12420
gtggacccgg cgctgcgggc ggctctgcag agccagccgt ccggccttaa ctcctcagac 12480
gactggcgac aggtcatgga ccgcatcatg tcgctgacgg cgcgtaaccc ggacgcgttc 12540
cggcagcagc cgcaggccaa caggctctcc gccatcctgg aggcggtggt gcctgcgcgc 12600
tcgaacccca cgcacgagaa ggtgctggcc atagtgaacg cgctggccga gaacagggcc 12660
atccgcccgg acgaggccgg gctggtgtac gacgcgctgc tgcagcgcgt ggcccgctac 12720
aacagcggca acgtgcagac caacctggac cggctggtgg gggacgtgcg cgaggcggtg 12780
gcgcagcgcg agcgcgcgga tcggcagggc aacctgggct ccatggtggc gctgaatgcc 12840
ttcctgagca cgcagccggc caacgtgccg cgggggcagg aagactacac caactttgtg 12900
agcgcgctgc ggctgatggt gaccgagacc ccccagagcg aggtgtacca gtcgggcccg 12960
gactacttct tccagaccag cagacagggc ctgcagacgg tgaacctgag ccaggctttc 13020
aagaacctgc gggggctgtg gggcgtgaag gcgcccaccg gcgaccgggc gacggtgtcc 13080
agcctgctga cgcccaactc gcgcctgctg ctgctgctga tcgcgccgtt cacggacagc 13140
ggcagcgtgt cccgggacac ctacctgggg cacctgctga ccctgtaccg cgaggccatc 13200
gggcaggcgc aggtggacga gcacaccttc caggagatca ccagcgtgag ccgcgcgctg 13260
gggcaggagg acacgagcag cctggaggcg actctgaact acctgctgac caaccggcgg 13320
cagaagattc cctcgctgca cagcctgacc tccgaggagg agcgcatctt gcgctacgtg 13380
cagcagagcg tgagcctgaa cctgatgcgc gacggggtga cgcccagcgt ggcgctggac 13440
atgaccgcgc gcaacatgga accgggcatg tacgccgcgc accggcctta catcaaccgc 13500
ctgatggact acctgcatcg cgcggcggcc gtgaaccccg agtactttac caacgccatc 13560
ctgaacccgc actggctccc gccgcccggg ttctacagcg ggggcttcga ggtcccggag 13620
gccaacgatg gcttcctgtg ggacgacatg gacgacagcg tgttctcccc gcggccgcag 13680
gcgctggcgg aagcgtccct gctgcgtccc aagaaggagg aggaggaggc gagtcgccgc 13740
cgcggcagca gcggcgtggc ttctctgtcc gagctggggg cggcagccgc cgcgcgcccc 13800
gggtccctgg gcggcagccc ctttccgagc ctggtggggt ctctgcacag cgagcgcacc 13860
acccgccctc ggctgctggg cgaggacgag tacctgaata actccctgct gcagccggtg 13920
cgggagaaaa acctgccccc cgccttcccc aacaacggga tagagagcct ggtggacaag 13980
atgagcagat ggaagaccta tgcgcaggag cacagggacg cgcccgcgct ccggccgccc 14040
acgcggcgcc agcgccacga ccggcagcgg gggctggtgt gggatgacga ggactccgcg 14100
gacgatagca gcgtgctgga cctgggaggg agcggcaacc cgttcgcgca cctgcgcccc 14160
cgcctgggga ggatgtttta aaaaaaaaaa aagcaagaag catgatgcaa aattaaataa 14220
aactcaccaa ggccatggcg accgagcgtt ggtttcttgt gttcccttca gtatgcggcg 14280
cgcggcgatg taccaggagg gacctcctcc ctcttacgag agcgtggtgg gcgcggcggc 14340
ggcggcgccc tcttctccct ttgcgtcgca gctgctggag ccgccgtacg tgcctccgcg 14400
ctacctgcgg cctacggggg ggagaaacag catccgttac tcggagctgg cgcccctgtt 14460
cgacaccacc cgggtgtacc tggtggacaa caagtcggcg gacgtggcct ccctgaacta 14520
ccagaacgac cacagcaatt ttttgaccac ggtcatccag aacaatgact acagcccgag 14580
cgaggccagc acccagacca tcaatctgga tgaccggtcg cactggggcg gcgacctgaa 14640
aaccatcctg cacaccaaca tgcccaacgt gaacgagttc atgttcacca ataagttcaa 14700
ggcgcgggtg atggtgtcgc gctcgcacac caaggaagac cgggtggagc tgaagtacga 14760
gtgggtggag ttcgagctgc cagagggcaa ctactccgag accatgacca ttgacctgat 14820
gaacaacgcg atcgtggagc actatctgaa agtgggcagg caaaacgggg tcctggagag 14880
cgacatcggg gtcaagttcg acaccaggaa cttccgcctg gggctggacc ccgtgaccgg 14940
gctggttatg cccggggtgt acaccaacga ggccttccat cccgacatca tcctgctgcc 15000
cggctgcggg gtggacttca cttacagccg cctgagcaac ctcctgggca tccgcaagcg 15060
gcagcccttc caggagggct tcaggatcac ctacgaggac ctggaggggg gcaacatccc 15120
cgcgctcctc gatgtggagg cctaccagga tagcttgaag gaaaatgagg cgggacagga 15180
ggataccacc cccgccgcct ccgccgccgc cgagcagggc gaggatgctg ctgacaccgc 15240
ggccgcggac ggggcagagg ccgaccccgc tatggtggtg gaggctcccg agcaggagga 15300
ggatatgaat gacagtgcgg tgcgcggaga caccttcgtc acccgggggg aggaaaagca 15360
agcggaggcc gaggccgcgg ccgaggaaaa gcaactggcg gcagcagcgg cggcggcggc 15420
gttggccgcg gcggaggctg agtctgaggg gaccaagccc gccaaggagc ccgtgattaa 15480
gcccctgacc gaagatagca agaagcgcag ttacaacctg ctcaaggaca gcaccaacac 15540
cgcgtaccgc agctggtacc tggcctacaa ctacggcgac ccgtcgacgg gggtgcgctc 15600
ctggaccctg ctgtgcacgc cggacgtgac ctgcggctcg gagcaggtgt actggtcgct 15660
gcccgacatg atgcaagacc ccgtgacctt ccgctccacg cggcaggtca gcaacttccc 15720
ggtggtgggc gccgagctgc tgcccgtgca ctccaagagc ttctacaacg accaggccgt 15780
ctactcccag ctcatccgcc agttcacctc tctgacccac gtgttcaatc gctttcctga 15840
gaaccagatt ctggcgcgcc cgcccgcccc caccatcacc accgtcagtg aaaacgttcc 15900
tgctctcaca gatcacggga cgctaccgct gcgcaacagc atcggaggag tccagcgagt 15960
gaccgttact gacgccagac gccgcacctg cccctacgtt tacaaggcct tgggcatagt 16020
ctcgccgcgc gtcctttcca gccgcacttt ttgagcaaca ccaccatcat gtccatcctg 16080
atctcaccca gcaataactc cggctgggga ctgctgcgcg cgcccagcaa gatgttcgga 16140
ggggcgagga agcgttccga gcagcacccc gtgcgcgtgc gcgggcactt ccgcgccccc 16200
tggggagcgc acaaacgcgg ccgcgcgggg cgcaccaccg tggacgacgc catcgactcg 16260
gtggtggagc aggcgcgcaa ctacaggccc gcggtctcta ccgtggacgc ggccatccag 16320
accgtggtgc ggggcgcgcg gcggtacgcc aagctgaaga gccgccggaa gcgcgtggcc 16380
cgccgccacc gccgccgacc cggggccgcc gccaaacgcg ccgccgcggc cctgcttcgc 16440
cgggccaagc gcacgggccg ccgcgccgcc atgagggccg cgcgccgctt ggccgccggc 16500
atcaccgccg ccaccatggc cccccgtacc cgaagacgcg cggccgccgc cgccgccgcc 16560
gccatcagtg acatggccag caggcgccgg ggcaacgtgt actgggtgcg cgactcggtg 16620
accggcacgc gcgtgcccgt gcgcttccgc cccccgcgga cttgagatga tgtgaaaaaa 16680
caacactgag tctcctgctg ttgtgtgtat cccagcggcg gcggcgcgcg cagcgtcatg 16740
tccaagcgca aaatcaaaga agagatgctc caggtcgtcg cgccggagat ctatgggccc 16800
ccgaagaagg aagagcagga ttcgaagccc cgcaagataa agcgggtcaa aaagaaaaag 16860
aaagatgatg acgatgccga tggggaggtg gagttcctgc gcgccacggc gcccaggcgc 16920
ccggtgcagt ggaagggccg gcgcgtaaag cgcgtcctgc gccccggcac cgcggtggtc 16980
ttcacgcccg gcgagcgctc cacccggact ttcaagcgcg tctatgacga ggtgtacggc 17040
gacgaagacc tgctggagca ggccaacgag cgcttcggag agtttgctta cgggaagcgt 17100
cagcgggcgc tggggaagga ggacctgctg gcgctgccgc tggaccaggg caaccccacc 17160
cccagtctga agcccgtgac cctgcagcag gtgctgccga gcagcgcacc ctccgaggcg 17220
aagcggggtc tgaagcgcga gggcggcgac ctggcgccca ccgtgcagct catggtgccc 17280
aagcggcaga ggctggagga tgtgctggag aaaatgaaag tagaccccgg tctgcagccg 17340
gacatcaggg tccgtcccat caagcaggtg gcgccgggcc tcggcgtgca gaccgtggac 17400
gtggtcatcc ccaccggcaa ctcccccgcc gccaccacca ctaccgctgc ctccacggac 17460
atggagacac agaccgatcc cgccgcagcc gcagccgccg ccgcagccgc gacctcctcg 17520
gcggaggtgc agacggaccc ctggctgccg ccggcgatgt cagctccccg cgcgcgccgc 17580
ggacgcagaa agtacggcgc cgccaacgcg ctcctgcccg agtacgcctt gcatccttcc 17640
atcgcgccca cccccggcta ccgaggctat acctaccgcc cgcgaagagc caagggttcc 17700
acccgccgtc cccgccgacg cgccgccgcc accacccgcc gccgccgccg cagacgccag 17760
cccgcactgg ctccagtctc cgtgaggaga gtggcgcgcg acggacacac cctggtgctg 17820
cccagggcgc gctaccaccc cagcatcgtt taaaagcctg ttgtggttct tgcagatatg 17880
gccctcactt gccgcctccg tttcccggtg ccgggatacc gaggaggaag atcgcgccgc 17940
aggaggggtc tggccggccg cggcctgagc ggaggcagcc gccgcgcgca ccggcggcga 18000
cgcgccacca gccgacgcat gcgcggcggg gtgctgcccc tgttaatccc cctgatcgcc 18060
gcggcgatcg gcgccgtgcc cgggatcgcc tccgtggcct tgcaagcgtc ccagaggcat 18120
tgacagactt gcaaacttgc aaatatggaa aaaaaaaaaa aaccccaata aaaagtctag 18180
actctcacgc tcgcttggtc ctgtgactat tttgtagaat ggaagacatc aactttgcgt 18240
cgctggcccc gcgtcacggc tcgcgcccgt tcctgggaca ctggaacgat atcggcacca 18300
gcaacatgag cggtggcgcc ttcagttggg gctctctgtg gagcggcatt aaaagtatcg 18360
ggtctgccgt taaaaattac ggctcccggg cctggaacag cagcacgggc cagatgttga 18420
gagacaagtt gaaagagcag aacttccagc agaaggtggt ggagggcctg gcctccggca 18480
tcaacggggt ggtggacctg gccaaccagg ccgtgcagaa taaaatcaac agcagactgg 18540
acccccggcc gccggtggag gaggtgccgc cggcgctgga gacggtgtcc cccgatgggc 18600
gtggcgagaa gcgcccgcgg cccgataggg aagagaccac tctggtcacg cagaccgatg 18660
agccgccccc gtatgaggag gccctaaagc aaggtctgcc caccacgcgg cccatcgcgc 18720
ccatggccac cggggtggtg ggccgccaca cccccgccac gctggacttg cctccgcccg 18780
ccgatgtgcc gcagcagcag aaggcggcac agccgggccc gcccgcgacc gcctcccgtt 18840
cctccgccgg tcctctgcgc cgcgcggcca gcggcccccg cgggggggtc gcgaggcacg 18900
gcaactggca gagcacgctg aacagcatcg tgggtctggg ggtgcggtcc gtgaagcgcc 18960
gccgatgcta ctgaatagct tagctaacgt gttgtatgtg tgtatgcgcc ctatgtcgcc 19020
gccagaggag ctgctgagtc gccgccgttc gcgcgcccac caccaccgcc actccgcccc 19080
tcaagatggc gaccccatcg atgatgccgc agtggtcgta catgcacatc tcgggccagg 19140
acgcctcgga gtacctgagc cccgggctgg tgcagttcgc ccgcgccacc gagagctact 19200
tcagcctgag taacaagttt aggaacccca cggtggcgcc cacgcacgat gtgaccaccg 19260
accggtctca gcgcctgacg ctgcggttca ttcccgtgga ccgcgaggac accgcgtact 19320
cgtacaaggc gcggttcacc ctggccgtgg gcgacaaccg cgtgctggac atggcctcca 19380
cctactttga catccgcggg gtgctggacc ggggtcccac tttcaagccc tactctggca 19440
ccgcctacaa ctccctggcc cccaagggcg ctcccaactc ctgcgagtgg gagcaagagg 19500
aaactcaggc agttgaagaa gcagcagaag aggaagaaga agatgctgac ggtcaagctg 19560
aggaagagca agcagctacc aaaaagactc atgtatatgc tcaggctccc ctttctggcg 19620
aaaaaattag taaagatggt ctgcaaatag gaacggacgc tacagctaca gaacaaaaac 19680
ctatttatgc agaccctaca ttccagcccg aaccccaaat cggggagtcc cagtggaatg 19740
aggcagatgc tacagtcgcc ggcggtagag tgctaaagaa atctactccc atgaaaccat 19800
gctatggttc ctatgcaaga cccacaaatg ctaatggagg tcagggtgta ctaacggcaa 19860
atgcccaggg acagctagaa tctcaggttg aaatgcaatt cttttcaact tctgaaaacg 19920
cccgtaacga ggctaacaac attcagccca aattggtgct gtatagtgag gatgtgcaca 19980
tggagacccc ggatacgcac ctttcttaca agcccgcaaa aagcgatgac aattcaaaaa 20040
tcatgctggg tcagcagtcc atgcccaaca gacctaatta catcggcttc agagacaact 20100
ttatcggcct catgtattac aatagcactg gcaacatggg agtgcttgca ggtcaggcct 20160
ctcagttgaa tgcagtggtg gacttgcaag acagaaacac agaactgtcc taccagctct 20220
tgcttgattc catgggtgac agaaccagat acttttccat gtggaatcag gcagtggaca 20280
gttatgaccc agatgttaga attattgaaa atcatggaac tgaagacgag ctccccaact 20340
attgtttccc tctgggtggc ataggggtaa ctgacactta ccaggctgtt aaaaccaaca 20400
atggcaataa cgggggccag gtgacttgga caaaagatga aacttttgca gatcgcaatg 20460
aaataggggt gggaaacaat ttcgctatgg agatcaacct cagtgccaac ctgtggagaa 20520
acttcctgta ctccaacgtg gcgctgtacc taccagacaa gcttaagtac aacccctcca 20580
atgtggacat ctctgacaac cccaacacct acgattacat gaacaagcga gtggtggccc 20640
cggggctggt ggactgctac atcaacctgg gcgcgcgctg gtcgctggac tacatggaca 20700
acgtcaaccc cttcaaccac caccgcaatg cgggcctgcg ctaccgctcc atgctcctgg 20760
gcaacgggcg ctacgtgccc ttccacatcc aggtgcccca gaagttcttt gccatcaaga 20820
acctcctcct cctgccgggc tcctacacct acgagtggaa cttcaggaag gatgtcaaca 20880
tggtcctcca gagctctctg ggtaacgatc tcagggtgga cggggccagc atcaagttcg 20940
agagcatctg cctctacgcc accttcttcc ccatggccca caacacggcc tccacgctcg 21000
aggccatgct caggaacgac accaacgacc agtccttcaa tgactacctt tccgccgcca 21060
acatgctcta ccccataccc gccaacgcca ccaacgtccc catctccatc ccctcgcgca 21120
actgggcggc cttccgcggc tgggccttca cccgcctcaa gaccaaggag accccctccc 21180
tgggctcggg attcgacccc tactacacct actcgggctc tattccctac ctggacggca 21240
ccttctacct caaccacact ttcaagaagg tctcggtcac cttcgactcc tcggtcagct 21300
ggccgggcaa cgaccgtctg ctcaccccca acgagttcga gatcaagcgc tcggtcgacg 21360
gggaaggcta caacgtggcc cagtgcaaca tgaccaagga ctggttcctg gtccagatgc 21420
tggccaacta caacatcggc taccagggct tctacatccc agagagctac aaggacagga 21480
tgtactcctt cttcaggaac ttccagccca tgagccggca ggtggtggac cagaccaagt 21540
acaaggacta ccaggaggtg ggcatcatcc accagcacaa caactcgggc ttcgtgggct 21600
acctcgcccc caccatgcgc gagggacagg cctaccccgc caacttcccc tacccgctca 21660
taggcaagac cgcggtcgac agcatcaccc agaaaaagtt cctctgcgac cgcaccctct 21720
ggcgcatccc cttctccagc aacttcatgt ccatgggtgc gctctcggac ctgggccaga 21780
acttgctcta cgccaactcc gcccacgccc tcgacatgac cttcgaggtc gaccccatgg 21840
acgagcccac ccttctctat gttctgttcg aagtctttga cgtggtccgg gtccaccagc 21900
cgcaccgcgg cgtcatcgag accgtgtacc tgcgtacgcc cttctcggcc ggcaacgcca 21960
ccacctaaag aagcaagccg cagtcatcgc cgcctgcatg ccgtcgggtt ccaccgagca 22020
agagctcagg gccatcgtca gagacctggg atgcgggccc tattttttgg gcaccttcga 22080
caagcgcttc cctggctttg tctccccaca caagctggcc tgcgccatcg tcaacacggc 22140
cggccgcgag accgggggcg tgcactggct ggcctttgcc tggaacccgc gctccaaaac 22200
atgcttcctc tttgacccct tcggcttttc ggaccagcgg ctcaagcaaa tctacgagtt 22260
cgagtacgag ggcttgctgc gtcgcagcgc catcgcctcc tcgcccgacc gctgcgtcac 22320
cctcgaaaag tccacccaga ccgtgcaggg gcccgactcg gccgcctgcg gtctcttctg 22380
ctgcatgttt ctgcacgcct ttgtgcactg gcctcagagt cccatggacc gcaaccccac 22440
catgaacttg ctgacggggg tgcccaactc catgctccaa agcccccagg tcgagcccac 22500
cctgcgccgc aaccaggagc agctctacag cttcctggag cgccactcgc cctacttccg 22560
ccgccacagc gcacagatca ggagggccac ctccttctgc cacttgcaag agatgcaaga 22620
agggtaataa cgatgtacac acttttttct caataaatgg catttttttt ttatttatac 22680
aagctctctg gggtattcat ttcccaccac caccacccgc cgttgtcgcc atctggctct 22740
atttagaaat cgaaagggtt ctgccgggag tcgccgtgcg ccacgggcag ggacacgttg 22800
cgatactggt agcgggtgcc ccacttgaac tcgggcacca ccaggcgagg cagctcgggg 22860
aagttttcgc tccacaggct gcgggtcagc accagcgcgt tcatcaggtc gggcgccgag 22920
atcttgaagt cgcagttggg gccgccgccc tgcgcgcgcg agttgcggta caccgggttg 22980
cagcactgga acaccaacag cgccgggtgc ttcacgctgg ccagcacgct gcggtcggag 23040
atcagctcgg cgtccaggtc ctccgcgttg ctcagcgcga acggggtcat cttgggcact 23100
tgccgcccca ggaagggcgc gtgccccggt ttcgagttgc agtcgcagcg cagcgggatc 23160
agcaggtgcc cgtgcccgga ctcggcgttg gggtacagcg cgcgcatgaa ggcctgcatc 23220
tggcggaagg ccatctgggc cttggcgccc tccgagaaga acatgccgca ggacttgccc 23280
gagaactggt ttgcggggca gctggcgtcg tgcaggcagc agcgcgcgtc ggtgttggcg 23340
atctgcacca cgttgcgccc ccaccggttc ttcacgatct tggccttgga cgattgctcc 23400
ttcagcgcgc gctgcccgtt ctcgctggtc acatccatct cgatcacatg ttccttgttc 23460
accatgctgc tgccgtgcag acacttcagc tcgccctccg tctcggtgca gcggtgctgc 23520
cacagcgcgc agcccgtggg ctcgaaagac ttgtaggtca cctccgcgaa ggactgcagg 23580
tacccctgca aaaagcggcc catcatggtc acgaaggtct tgttgctgct gaaggtcagc 23640
tgcagcccgc ggtgctcctc gttcagccag gtcttgcaca cggccgccag cgcctccacc 23700
tggtcgggca gcatcttgaa gttcaccttc agctcattct ccacgtggta cttgtccatc 23760
agcgtgcgcg ccgcctccat gcccttctcc caggccgaca ccagcggcag gctcacgggg 23820
ttcttcacca tcaccgtggc cgccgcctcc gccgcgcttt cgctttccgc cccgctgttc 23880
tcttcctctt cctcctcttc ctcgccgccg cccactcgca gcccccgcac cacggggtcg 23940
tcttcctgca ggcgctgcac cttgcgcttg ccgttgcgcc cctgcttgat gcgcacgggc 24000
gggttgctga agcccaccat caccagcgcg gcctcttctt gctcgtcctc gctgtccaga 24060
atgacctccg gggagggggg gttggtcatc ctcagtaccg aggcacgctt ctttttcttc 24120
ctgggggcgt tcgccagctc cgcggctgcg gccgctgccg aggtcgaagg ccgagggctg 24180
ggcgtgcgcg gcaccagcgc gtcttgcgag ccgtcctcgt cctcctcgga ctcgagacgg 24240
aggcgggccc gcttcttcgg gggcgcgcgg ggcggcggag gcggcggcgg cgacggagac 24300
ggggacgaga catcgtccag ggtgggtgga cggcgggccg cgccgcgtcc gcgctcgggg 24360
gtggtttcgc gctggtcctc ttcccgactg gccatctccc actgctcctt ctcctatagg 24420
cagaaagaga tcatggagtc tctcatgcga gtcgagaagg aggaggacag cctaaccgcc 24480
ccctctgagc cctccaccac cgccgccacc accgccaatg ccgccgcgga cgacgcgccc 24540
accgagacca ccgccagtac caccctcccc agcgacgcac ccccgctcga gaatgaagtg 24600
ctgatcgagc aggacccggg ttttgtgagc ggagaggagg atgaggtgga tgagaaggag 24660
aaggaggagg tcgccgcctc agtgccaaaa gaggataaaa agcaagacca ggacgacgca 24720
gataaggatg agacagcagt cgggcggggg aacggaagcc atgatgctga tgacggctac 24780
ctagacgtgg gagacgacgt gctgcttaag cacctgcacc gccagtgcgt catcgtctgc 24840
gacgcgctgc aggagcgctg cgaagtgccc ctggacgtgg cggaggtcag ccgcgcctac 24900
gagcggcacc tcttcgcgcc gcacgtgccc cccaagcgcc gggagaacgg cacctgcgag 24960
cccaacccgc gtctcaactt ctacccggtc ttcgcggtac ccgaggtgct ggccacctac 25020
cacatcttct tccaaaactg caagatcccc ctctcctgcc gcgctaaccg cacccgcgcc 25080
gacaaaaccc tgaccctgcg gcagggcgcc cacatacctg atattgcctc tctggaggaa 25140
gtgcccaaga tcttcgaggg tctcggtcgc gacgagaaac gggcggcgaa cgctctgcac 25200
ggagacagcg aaaacgagag tcactcgggg gtgctggtgg agctcgaggg cgacaacgcg 25260
cgcctggccg tactcaagcg cagcatagag gtcacccact ttgcctaccc ggcgctcaac 25320
ctgcccccca aggtcatgag tgtggtcatg ggcgagctca tcatgcgccg cgctcagccc 25380
ctggccgcgg atgcaaactt gcaagagtcc tccgaggaag gcctgcccgc ggtcagcgac 25440
gagcagctag cgcgctggct ggagacccgc gaccccgcgc agctggagga gcggcgcaag 25500
ctcatgatgg ccgcggtgct ggtcaccgtg gagctcgagt gtctgcagcg cttcttcgcg 25560
gaccccgaga tgcagcgcaa gctcgaggag accctgcact acaccttccg ccagggctac 25620
gtgcgccagg cctgcaagat ctccaacgtg gagctctgca acctggtctc ctacctgggc 25680
atcctgcacg agaaccgcct cgggcagaac gtcctgcact ccaccctcaa aggggaggcg 25740
cgccgcgact acatccgcga ctgcgcctac ctcttcctct gctacacctg gcagacggcc 25800
atgggggtct ggcagcagtg cctggaggag cgcaacctca aggagctgga aaagctactc 25860
aagcgcaccc tcagggacct ctggacgggc ttcaacgagc gctcggtggc cgccgcgctg 25920
gcggacatca tcttccccga gcgcctgctc aagaccctgc agcagggcct gcccgacttc 25980
accagccaga gcatgctgca gaactttagg actttcatcc tggagcgctc gggcatcctg 26040
cctgccactt gctgcgcgct gcccagcgac ttcgtgccca tcaagtacag ggagtgcccg 26100
ccgccgctct ggggccactg ctacctcttc cagctggcca actacctcgc ctaccactcg 26160
gacctcatgg aagacgtgag cggcgagggc ctgctcgagt gccactgccg ctgcaacctc 26220
tgcacgcccc accgctctct agtctgcaac ccgcagctgc tcagcgagag tcagattatc 26280
ggtaccttcg agctgcaggg tccctcgcct gacgagaagt ccgcggctcc ggggctgaaa 26340
ctcactccgg ggctgtggac ttccgcctac ctacgcaaat ttgtacctga ggactaccac 26400
gcccacgaga tcaggttcta cgaagaccaa tcccgcccgc ccaaggcgga gctcaccgcc 26460
tgcgtcatca cccaggggca catcctgggc caattgcaag ccatcaacaa agcccgccga 26520
gagttcttgc tgaaaaaggg tcggggggtg tacctggacc cccagtccgg cgaggagcta 26580
aacccgctac ccccgccgcc gccccagcag cgggaccttg cttcccagga tggcacccag 26640
aaagaagcag cagccgccgc cgccgcagcc atacatgctt ctggaggaag aggaggagga 26700
ctgggacagt caggcagagg aggtttcgga cgaggagcag gaggagatga tggaagactg 26760
ggaggaggac agcagcctag acgaggaagc ttcagaggcc gaagaggtgg cagacgcaac 26820
accatcaccc tcggtcgcag ccccctcgcc ggggcccctg aaatcctccg aacccagcac 26880
cagcgctata acctccgctc ctccggcgcc ggcgccaccc gcccgcagac ccaaccgtag 26940
atgggacacc acaggaaccg gggtcggtaa gtccaagtgc ccgccgccgc caccgcagca 27000
gcagcagcag cgccagggct accgctcgtg gcgcgggcac aagaacgcca tagtcgcctg 27060
cttgcaagac tgcgggggca acatctcttt cgcccggcgc ttcctgctat tccaccacgg 27120
ggtcgccttt ccccgcaatg tcctgcatta ctaccgtcat ctctacagcc cctactgcag 27180
cggcgaccca gaggcggcag cggcagccac agcggcgacc accacctagg aagatatcct 27240
ccgcgggcaa gacagcggca gcagcggcca ggagacccgc ggcagcagcg gcgggagcgg 27300
tgggcgcact gcgcctctcg cccaacgaac ccctctcgac ccgggagctc agacacagga 27360
tcttccccac tttgtatgcc atcttccaac agagcagagg ccaggagcag gagctgaaaa 27420
taaaaaacag atctctgcgc tccctcaccc gcagctgtct gtatcacaaa agcgaagatc 27480
agcttcggcg cacgctggag gacgcggagg cactcttcag caaatactgc gcgctcactc 27540
ttaaagacta gctccgcgcc cttctcgaat ttaggcggga gaaaactacg tcatcgccgg 27600
ccgccgccca gcccgcccag ccgagatgag caaagagatt cccacgccat acatgtggag 27660
ctaccagccg cagatgggac tcgcggcggg agcggcccag gactactcca cccgcatgaa 27720
ctacatgagc gcgggacccc acatgatctc acaggtcaac gggatccgcg cccagcgaaa 27780
ccaaatactg ctggaacagg cggccatcac cgccacgccc cgccataatc tcaacccccg 27840
aaattggccc gccgccctcg tgtaccagga aaccccctcc gccaccaccg tactacttcc 27900
gcgtgacgcc caggccgaag tccagatgac taactcaggg gcgcagctcg cgggcggctt 27960
tcgtcacggg gcgcggccgc tccgaccagg tataagacac ctgatgatca gaggccgagg 28020
tatccagctc aacgacgagt cggtgagctc ttcgctcggt ctccgtccgg acggaacttt 28080
ccagctcgcc ggatccggcc gctcttcgtt cacgccccgc caggcgtacc tgactctgca 28140
gacctcgtcc tcggagcccc gctccggagg catcggaacc ctccagttcg tggaggagtt 28200
cgtgccctcg gtctacttca accccttctc gggacctccc ggacgctacc ccgaccagtt 28260
cattccgaac tttgacgcgg tgaaggactc ggcggacggc tacgactgaa tgtcaggtgc 28320
cgaggcagag cagcttcgcc tgagacacct cgagcactgc cgccgccaca agtgcttcgc 28380
ccgcggttcc ggtgagttct gctactttca gctacccgag gagcataccg aggggccggc 28440
gcacggcgtc cgcctgacca cccagggcga ggttacctgt tccctcatcc gggagttcac 28500
cctccgtccc ctgctagtgg agcgggagcg gggtccctgt gtcctaacta tcgcctgcaa 28560
ctgccctaac cctggattac atcaagatct ttgctgtcat ctctgtgctg agtttaataa 28620
acgctgagat cagaatctac tggggctcct gtcgccatcc tgtgaacgcc accgtcttca 28680
cccaccccga ccaggcccag gcgaacctca cctgcggtct gcatcggagg gccaagaagt 28740
acctcacctg gtacttcaac ggcaccccct ttgtggttta caacagcttc gacggggacg 28800
gagtctccct gaaagaccag ctctccggtc tcagctactc catccacaag aacaccaccc 28860
tccaactctt ccctccctac ctgccgggaa cctacgagtg cgtcaccggc cgctgcaccc 28920
acctcacccg cctgatcgta aaccagagct ttccgggaac agataactcc ctcttcccca 28980
gaacaggagg tgagctcagg aaactccccg gggaccaggg cggagacgta ccttcgaccc 29040
ttgtggggtt aggatttttt attaccgggt tgctggctct tttaatcaaa gcttccttga 29100
gatttgttct ttccttctac gtgtatgaac acctcagcct ccaataactc taccctttct 29160
tcggaatcag gtgacttctc tgaaatcggg cttggtgtgc tgcttactct gttgattttt 29220
ttccttatca tactcagcct tctgtgcctc aggctcgccg cctgctgcgc acacatctat 29280
atctactgct ggttgctcaa gtgcaggggt cgccacccaa gatgaacagg tacatggtcc 29340
tatcgatcct aggcctgctg gccctggcgg cctgcagcgc cgccaaaaaa gagattacct 29400
ttgaggagcc cgcttgcaat gtaactttca agcccgaggg tgaccaatgc accaccctcg 29460
tcaaatgcgt taccaatcat gagaggctgc gcatcgacta caaaaacaaa actggccagt 29520
ttgcggtcta tagtgtgttt acgcccggag acccctctaa ctactctgtc accgtcttcc 29580
agggcggaca gtctaagata ttcaattaca ctttcccttt ttatgagtta tgcgatgcgg 29640
tcatgtacat gtcaaaacag tacaacctgt ggcctccctc tccccaggcg tgtgtggaaa 29700
atactgggtc ttactgctgt atggctttgg caatcactac gctcgctcta atctgcacgg 29760
tgctatacat aaaattcagg cagaggcgaa tctttatcga tgaaaagaaa atgccttgat 29820
cgctaacacc ggctttctat ctgcagaatg aatgcaatca cctccctact aatcaccacc 29880
accctccttg cgattgccca tgggttgaca cgaatcgaag tgccagtggg gtccaatgtc 29940
accatggtgg gccccgccgg caattccacc ctcatgtggg aaaaatttgt ccgcaatcaa 30000
tgggttcatt tctgctctaa ccgaatcagt atcaagccca gagccatctg cgatgggcaa 30060
aatctaactc tgatcaatgt gcaaatgatg gatgctgggt actattacgg gcagcgggga 30120
gaaatcatta attactggcg accccacaag gactacatgc tgcatgtagt cgaggcactt 30180
cccactacca cccccactac cacctctccc accaccacta ccaccactac tactactact 30240
actaccacta ccgctgcccg ccatacccgc aaaagcacca tgattagcac aaagccccct 30300
cgtgctcact cccacgccgg cgggcccatc ggtgcgacct cagaaaccac cgagctttgc 30360
ttctgccaat gcactaacgc cagcgctcat gaactgttcg acctggagaa tgaggatgcc 30420
cagcagagct ccgcttgcct gacccaggag gctgtggagc ccgttgccct gaagcagatc 30480
ggtgattcaa taattgactc ttcttctttt gccactcccg aataccctcc cgattctact 30540
ttccacatca cgggtaccaa agaccctaac ctctctttct acctgatgct gctgctctgt 30600
atctctgtgg tctcttccgc gctgatgtta ctggggatgt tctgctgcct gatctgccgc 30660
agaaagagaa aagctcgctc tcagggccaa ccactgatgc ccttccccta ccccccggat 30720
tttgcagata acaagatatg agctcgctgc tgacactaac cgctttacta gcctgcgctc 30780
taacccttgt cgcttgcgac tcgagattcc acaatgtcac agctgtggca ggagaaaatg 30840
ttactttcaa ctccacggcc gatacccagt ggtcgtggag tggctcaggt agctacttaa 30900
ctatctgcaa tagctccact tcccccagca tatccccaac caagtaccaa tgcaatgcca 30960
gcctgttcac cctcatcaac gcttccaccc tggacaatgg actctatgta ggctatgtac 31020
cctttggtgg gcaaggaaag acccacgctt acaacctgga agttcgccag cccagaacca 31080
ctacccaagc ttctcccacc accaccacca ccaccaccac caccatcacc agcagcagca 31140
gcagccacag cagcagcagc agattattga ctttggtttt ggccagctca tctgccgcta 31200
cccaggccat ctacagctct gtgcccgaaa ccactcagat ccaccgccca gaaacgacca 31260
ccgccaccac cctacacacc tccagcgatc agatgccgac caacatcacc cccttggctc 31320
ttcaaatggg acttacaagc cccactccaa aaccagtgga tgcggccgag gtctccgccc 31380
tcgtcaatga ctgggcgggg ctgggaatgt ggtggttcgc cataggcatg atggcgctct 31440
gcctgcttct gctctggctc atctgctgcc tccaccgcag gcgagccaga ccccccatct 31500
atagacccat cattgtcctg aaccccgata atgatgggat ccatagattg gatggcctga 31560
aaaacctact tttttctttt acagtatgat aaattgagac atgcctcgca ttttcttgta 31620
catgttcctt ctcccacctt ttctggggtg ttctacgctg gccgctgtgt ctcacctgga 31680
ggtagactgc ctctcaccct tcactgtcta cctgctttac ggattggtca ccctcactct 31740
catctgcagc ctaatcacag taatcatcgc cttcatccag tgcattgatt acatctgtgt 31800
gcgcctcgca tacttcagac accacccgca gtaccgagac aggaacattg cccaacttct 31860
aagactgctc taatcatgca taagactgtg atctgccttc tgatcctctg catcctgccc 31920
accctcacct cctgccagta caccacaaaa tctccgcgca aaagacatgc ctcctgccgc 31980
ttcacccaac tgtggaatat acccaaatgc tacaacgaaa agagcgagct ctccgaagct 32040
tggctgtatg gggtcatctg tgtcttagtt ttctgcagca ctgtctttgc cctcatgatc 32100
tacccctact ttgatttggg atggaacgcg atcgatgcca tgaattaccc cacctttccc 32160
gcacccgaga taattccact gcgacaagtt gtacccgttg tcgttaatca acgcccccca 32220
tcccctacgc ccactgaaat cagctacttt aacctaacag gcggagatga ctgacgccct 32280
agatctagaa atggacggca tcagtaccga gcagcgtctc ctagagaggc gcaggcaggc 32340
ggctgagcaa gagcgcctca atcaggagct ccgagatctc gttaacctgc accagtgcaa 32400
aagaggcatc ttttgtctgg taaagcaggc caaagtcacc tacgagaaga ccggcaacag 32460
ccaccgcctc agttacaaat tgcccaccca gcgccagaag ctggtgctca tggtgggtga 32520
gaatcccatc accgtcaccc agcactcggt agagaccgag gggtgtctgc actctccctg 32580
tcggggtcca gaagacctct gcaccctggt aaagaccctg tgcggtctca gagatttagt 32640
cccctttaac taatcaaaca ctggaatcaa taaaaagaat cacttactta aaatcagaca 32700
gcaggtctct gtccagttta ttcagcagca cctccttccc ctcctcccaa ctctggtact 32760
ccaaacgcct tctggcggca aacttcctcc acaccctgaa gggaatgtca gattcttgct 32820
cctgtccctc cgcacccact atcttcatgt tgttgcagat gaagcgcacc aaaacgtctg 32880
acgagagctt caaccccgtg tacccctatg acacggaaag cggccctccc tccgtccctt 32940
tcctcacccc tcccttcgtg tctcccgatg gattccaaga aagccccccc ggggtcctgt 33000
ctctgaacct ggccgagccc ctggtcactt cccacggcat gctcgccctg aaaatgggaa 33060
gtggcctctc cctggacgac gctggcaacc tcacctctca agatatcacc accgctagcc 33120
ctcccctcaa aaaaaccaag accaacctca gcctagaaac ctcatccccc ctaactgtaa 33180
gcacctcagg cgccctcacc gtagcagccg ccgctcccct ggcagtggcc ggcacctccc 33240
tcaccatgca atcagaggcc cccctgacag tacaggatgc aaaactcacc ctggccacca 33300
aaggccccct gaccgtgtct gaaggcaaac tggccttgca aacatcggcc ccgctgacgg 33360
ccgctgacag cagcaccctc accgttagcg ccacaccacc aattaatgta agcagtggaa 33420
gtttaggctt agacatggaa gaccctatgt atactcacga tggaaaactg ggaataagaa 33480
ttgggggtcc actaagagta gtagacagct tgcacacact cactgtagtt accggaaatg 33540
gactaactgt agataacaat gccctccaaa ctagagttac gggcgcccta ggttatgaca 33600
catcaggaaa tctacaattg agagctgcag gaggtatgcg aattgatgca aatggccaac 33660
ttatccttaa tgtggcatac ccatttgatg ctcagaacaa tctcagcctt agacttggtc 33720
agggacccct gtatataaac acagaccaca acctggattt gaattgcaac agaggtctaa 33780
ccacaactac caccaacaac acaaaaaaac ttgagactaa aattagctca ggcttagact 33840
atgacaccaa tggtgctgtc attattaaac ttggcactgg tctaagcttc gacaacacag 33900
gcgccctaac tgtgggaaac actggtgatg ataaactgac tctgtggacg accccagacc 33960
catctccaaa ttgcagaatt cactcagaca aagactgcaa gtttactcta gtcctaacta 34020
agtgtggaag ccaaatcctg gcctctgtcg ccgccctagc ggtatcagga aatctggctt 34080
cgataacagg caccgttgcc agcgttacca tctttctcag atttgatcag aatggagtgc 34140
ttatggaaaa ctcctcgcta gacaggcagt actggaactt cagaaatggc aactcaacta 34200
acgctgcccc ctacaccaat gcagttgggt tcatgccaaa cctcgcagca taccccaaaa 34260
cgcaaagcca gactgctaaa aacaacattg taagtcaggt ttacttgaat ggagacaaat 34320
ccaaacccat gacccttacc atcaccctca atggaactaa tgaatccagt gaaactagcc 34380
aggtgagtca ctactccatg tcatttacat gggcttggga aagtgggcaa tatgccactg 34440
aaacctttgc caccaactcc ttcacctttt cttacattgc tgaacaataa aaagcatgac 34500
actgatgttc atttctgatt cttattttat tattttcaaa cacaacaaaa tcattcaagt 34560
cattcttcca tcttagctta atagacacag tagcttaata gacccagtag tgcaaagccc 34620
cattctagct tatagatcag acagtgataa ttaaccacca ccaccaccat accttttgat 34680
tcaggaaatc atgatcatca caggatccta gtcttcaggc cgccccctcc ctcccaagac 34740
acagaataca cagtcctctc cccccgactg gctttaaata acaccatctg gttggtcaca 34800
gacatgttct taggggttat attccacacg gtctcctgcc gcgccaggcg ctcgtcggtg 34860
atgttgataa actctcccgg cagctcgctc aagttcacgt cgctgtccag cggctgaacc 34920
tccggctgac gcgataactg tgcgaccggc tgctggacaa acggaggccg cgcctacaag 34980
ggggtagagt cataatcctc ggtcaggata gggcggtgat gcagcagcag cgagcgaaac 35040
atctgctgcc gccgccgctc cgtccggcag gaaaacaaca agccggtggt ctcctccgcg 35100
ataatccgca ccgcccgcag catcagcttc ctcgttctcc gcgcgcagca cctcaccctg 35160
atctcgctca agtcggcgca gtaggtacag cacagcacca cgatgttatt catgatccca 35220
cagtgcaggg cgctgtatcc aaagctcatg ccgggaacca ccgcccccac gtggccatcg 35280
taccacaagc gcacgtaaat taagtgtcga cccctcatga acgtgctgga cacaaacatt 35340
acttccttgg gcatgttgta attcaccacc tcccggtacc agataaacct ctggttaaac 35400
agggcacctt ccaccaccat cctgaaccaa gaggccagaa cctgcccacc ggctatgcac 35460
tgcagggaac ccgggttgga acaatgacaa tgcagactcc aaggctcgta accgtggatc 35520
atccggctgc tgaaggcatc gatgttggca caacacagac acacgtgcat gcactttctc 35580
atgattagca gctcttccct cgtcaggatc atatcccaag gaataaccca ttcttgaatc 35640
aacgtaaaac ccacacagca gggaaggcct cgcacataac tcacgttgtg catggtcagc 35700
gtgttgcatt ctggaaacag cggatgatcc tccagtatcg aggcgcgggt ctccttctca 35760
cagggaggta aagggtccct gctgtacgga ctgcgccggg acgaccgaga tcgtgttgag 35820
cgtagtgtca tggaaaaggg aacgccggac gtggtcatac ttcttgaagc agaaccaggt 35880
tcgcgcgtgg caggcctcct tgcgtctgcg gtctcgccgt ctagctcgct ccgtgtgata 35940
gttgtagtac agccactccc gcagagcgtc gaggcgcacc ctggcttccg gatctatgta 36000
gactccgtct tgcaccgcgg ccctgataat atccaccacc gtagaataag caacacccag 36060
ccaagcaata cactcgctct gcgagcggca gacaggagga gcgggcagag atgggagaac 36120
catgataaaa aacttttttt aaagaatatt ttccaattct tcgaaagtaa gatctatcaa 36180
gtggcagcgc tcccctccac tggcgcggtc aaactctacg gccaaagcac agacaacggc 36240
atttctaaga tgttccttaa tggcgtccaa aagacacacc gctctcaagt tgcagtaaac 36300
tatgaatgaa aacccatccg gctgattttc caatatagac gcgccggcgg cgtccaccaa 36360
acccagataa ttttcttctc tccagcggtt tagaatctgt ctaagcaaat cccttatatc 36420
aagtccggcc atgccaaaaa tctgctcaag agcgccctcc accttcatga ccaagcagcg 36480
catcatgatt gcaaaaattc aggttcttca gagacctgta taagattcaa aatgggaaca 36540
ttaacaaaaa ttcctctgtc gcgcagatcc cttcgcaggg caagctgaac ataatcagac 36600
aggtctgaac ggaccagtga ggccaaatcc ccaccaggaa ccagatccag agaccctata 36660
ctgattatga cgcgcatact cggggctatg ctgaccagcg tagcgccgat gtaggcgtgc 36720
tgcatgggcg gcgagataaa atgcaaagtg ctggttaaaa aatcaggcaa agcctcgcgc 36780
aaaaaagcta acacatcata atcatgctca tgcaggtagt tgcaggtaag ctcaggaacc 36840
aaaacggaat aacacacgat tttcctctca aacatgactt cgcggatact gcgtaaaaca 36900
aaaattataa ataaaaaatt aattaactta aacattggaa gcctgtctca caacaggaaa 36960
aaccacttta atcaacataa gacgggccac gggcatgccg gcatagccgt aaaaaaattg 37020
gtccccgtga ttaacaagta ccacagacag ctccccggtc atgtcggggg tcatcatgtg 37080
agactctgta tacacgtctg gattgtgaac atcagacaaa caaagaaatc gagccacgta 37140
gcccggaggt ataatcaccc gcaggcggag gtacagcaaa acgaccccca taggaggaat 37200
cacaaaatta gtaggagaaa aaaatacata aacaccagaa aaaccctgtt gctgaggcaa 37260
aatagcgccc tcccgatcca aaacaacata aagcgcttcc acaggagcag ccataacaaa 37320
gacccgagtc ttaccagtaa aagaaaaaag atctctcaac gcagcaccag caccaacact 37380
tcgcagtgta aaaggccaag tgccgagaga gtatatatag gaataaaaag tgacgtaaac 37440
gggcaaagtc caaaaaacgc ccagaaaaac cgcacgcgaa cctacgcccc gaaacgaaag 37500
ccaaaaaaca ctagacactc ccttccggcg tcaacttccg ctttcccacg ctacgtcact 37560
tgccccagtc aaacaaacta catatcccga acttccaagt cgccacgccc aaaacaccgc 37620
ctacacctcc ccgcccgccg gcccgccccc aaacccgcct cccgccccgc gccccgcctc 37680
gcgccgccca tctcattatc atattggctt caatccaaaa taaggtatat tattgatgat 37740
g 37741
<210> 2
<211> 36648
<212> DNA
<213> 黑猩猩腺病毒-ChAd6基因组
<400> 2
catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agccgtttga 60
atttggggat gcggggcgct gattggctgc gggagcggcg accgttaggg gcggggcggg 120
tgacgttttg atgacgtgtt tgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180
gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240
ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300
aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360
ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420
ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480
tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540
cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600
gtaatgtttt cctggctact gggaacgaga ttctggaact ggtggtggac gccatgatgg 660
gtgacgaccc tcctgagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720
atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780
gcgatgccgc gctgctggcc gccgagcagg ctaatacgga ctctggctca gacagcgatt 840
cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900
aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960
aggaggcgat tcgagctgca gcgagcgagg gagtgaaagc tgcgggcgag agctttagcc 1020
tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080
ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140
acagtaagtg tgattaactt tagctgggaa ggcagagggt gactgggtgc tgactggttt 1200
atttatgtat atgtttttta tgtgtaggtc ccgtctctga cgtagatgag acccccactt 1260
cagagtgcat ttcatcaccc ccagaaattg gcgaggaacc gcccgaagat attattcata 1320
gaccagttgc agtgagagtc accgggcgga gagcagctgt ggagagtttg gatgacttgc 1380
tacagggtgg ggatgaacct ttggacttgt gtacccggaa acgccccagg cactaagtgc 1440
cacacatgtg tgtttactta aggtgatgtc agtatttata gggtgtggag tgcaataaaa 1500
tccgtgttga ctttaagtgt gtggtttatg actcaggggt ggggactgtg ggtatataag 1560
caggtgcaga cctgtgtggt cagttcagag caggactcat ggagatctgg acggtcttgg 1620
aagactttca ccagactaga cagctgctag agaactcatc ggaggaagtc tcttacctgt 1680
ggagattttg cttcggtggg gctctagcta agctagtcta tagggccaaa caggattata 1740
aggatcaatt tgaggatatt ttgagagagt gtcctagtat ttttgactct ctcaacttgg 1800
gccatcagtc tcactttaac cagagtattc tgagagccct tgacttttct actcctggca 1860
gaactaccgc cgcggtagcc ttttttgcct ttattcttga caaatggagt caagaaaccc 1920
atttcagcag ggattaccgt ctggactgct tagcagtagc tttgtggaga acatggaggt 1980
gccagcgcct gaatgcaatc tccggctact tgccagtaca gccggtagac acgctgagga 2040
tcctgagtct ccagtcaccc caggaacacc aacgccgcca gcagccgcag caggagcagc 2100
agcaagagga ggaggaggag gaggaccgag aagagaaccc gagagccggt ctggaccctc 2160
cggtggcgga ggaggaggag tagctgactt gtttcccgag ctgcgccggg tgctgactag 2220
gtcttccagt ggacgggaga gggggattaa gcgggagagg catgaggaga ctagtcacag 2280
aactgaactg actgtcagtc tgatgagccg caggcgccca gaatcggtgt ggtggcatga 2340
ggttcagtcg caggggatag atgaggtctc ggtaatgcat gagaaatatt ccctagaaca 2400
agtcaagact tgttggttgg agcccgagga tgattgggag gtagccatca ggaattatgc 2460
caagctggct ctgaggccag acaagaagta caagattacc aaactgatta atatcagaaa 2520
ttcctgctac atttcgggga atggggccga ggtggagatc agtacccagg agagggtggc 2580
cttcagatgt tgtatgatga atatgtaccc gggggtggtg ggcatggagg gagtcacctt 2640
tatgaacgcg aggtttaggg gtgatgggta taatggggtg gtctttatgg ccaacaccaa 2700
gctgacagtg cacggatgct ccttctttgg cttcaataac atgtgcatcg aggcctgggg 2760
cagtgtttca gtgaggggat gcagcttttc agccaactgg atgggggtcg tgggcagaac 2820
caagagcgtg gtgtcagtga agaaatgcct gttcgagagg tgccacctgg gggtgatgag 2880
cgagggcgaa gccaaagtca aacactgcgc ctctaccgag acgggctgct ttgtgatgat 2940
caagggcaat gccaaagtca agcataacat gatttgtggg gcctcggatg agcgcggcta 3000
ccagatgctg acctgtgccg gtgggaacag ccatatgctg gccaccgtgc atgtggcctc 3060
gcacccccgc aagacatggc ccgagttcga gcacaacgtc atgacccgct gcaatgtgca 3120
cctggggtcc cgccgaggca tgttcatgcc ctaccagtgc aacatgcaat ttgtgaaggt 3180
gctgctggag cccgatgcca tgtccagagt gagcctggtg ggggtgtttg acatgaatgt 3240
ggaggtgtgg aaaattctga gatatgatga atccaagacc aggtgccggg cctgcgaatg 3300
cggaggcaag cacgccaggc ttcagcccgt gtgtgtggag gtgacggagg acctgcgacc 3360
cgatcatttg gtgttgtcct gcaacgggac ggagttcggc tccagcgggg aagaatctga 3420
ctagagtgag tagtgtttgg gggtgggtgg gagtctgcat gatgggcaga atgactaaaa 3480
tctgtgtttt tctgcgcagc agcatgagcg gaagcgcctc ctttgaggga ggggtattca 3540
gcccttatct gacggggcgt ctcccctcct gggcgggagt gcgtcagaat gtgatgggat 3600
ccacggtgga cggccggccc gtgcagcccg cgaactcttc aaccctgacc tacgcgaccc 3660
tgagctcctc gtccgtggac gcagctgccg ccgcagctgc tgcttccgcc gccagcgccg 3720
tgcgcggaat ggccttgggc gccggctact acagctctct ggtggccaac tcgagttcca 3780
ccaataatcc cgccagcctg aacgaggaga agctgctgct gctgatggcc cagctcgagg 3840
ccctgaccca gcgcctgggc gagctgaccc agcaggtggc tcagctgcag gcggagacgc 3900
gggccgcggt tgccacggtg aaaaccaaat aaaaaatgaa tcaataaata aacggagacg 3960
gttgttgatt ttaacacaga gtcttgatct ttatttgatt tttcgcgcgc ggtaggccct 4020
ggaccaccgg tctcgatcat tgagcacccg gtggattttt tccaggaccc ggtagaggtg 4080
ggcttggatg ttgaggtaca tgggcatgag cccgtcccgg gggtggaggt agctccattg 4140
cagggcctcg tgctcggggg tggtgttgta aatcacccag tcatagcagg ggcgcagggc 4200
gtggtgctgc acgatgtcct tgaggaggag actgatggcc acgggcagcc ccttggtgta 4260
ggtgttgacg aacctgttga gctgggaggg atgcatgcgg ggggagatga gatgcatctt 4320
ggcctggatc ttgagattgg cgatgttccc gcccagatcc cgccgggggt tcatgttgtg 4380
caggaccacc agcacggtgt atccggtgca cttggggaat ttgtcatgca acttggaagg 4440
gaaggcgtga aagaatttgg agacgccctt gtgaccgccc aggttttcca tgcactcatc 4500
catgatgatg gcgatgggcc cgtgggcggc ggcctgggca aagacgtttc gggggtcgga 4560
cacatcgtag ttgtggtcct gggtgagctc gtcataggcc attttaatga atttggggcg 4620
gagagtgccc gactggggga cgaaggtgcc ctcgatcccg ggggcgtagt tcccctcgca 4680
gatctgcatc tcccaggcct tgagctcgga gggggggatc atgtccacct gcggggcgat 4740
gaaaaaaacg gtttccgggg cgggggagat gagctgggcc gaaagcaggt tccggagcag 4800
ctgggacttg ccgcagccgg tgggaccgta gatgaccccg atgaccggct gcaggtggta 4860
gttgagggag agacagctgc catcctcgcg gaggaggggg gccacctcgt tcatcatctc 4920
gcgcacatgc atgttctcgc gcacgagttc cgccaggagg cgctcgcccc ccagcgagag 4980
gagctcttgc agcgaggcga agtttttcag cggcttgagc ccgtcggcca tgggcatttt 5040
ggagagggtc tgttgcaaga gttccagacg gtcccagagc tcggtgatgt gctctagggc 5100
atctcgatcc agcagacctc ctcgtttcgc gggttggggc gactgcggga gtagggcacc 5160
aggcgatggg cgtccagcga ggccagggtc cggtccttcc agggtcgcag ggtccgcgtc 5220
agcgtggtct ccgtcacggt gaaggggtgc gcgccgggct gggcgcttgc gagggtgcgc 5280
ttcaggctca tccggctggt cgagaaccgc tcccggtcgg cgccctgcgc gtcggccagg 5340
tagcaattga gcatgagttc gtagttgagc gcctcggccg cgtggccctt ggcgcggagc 5400
ttacctttgg aagtgtgtcc gcagacggga cagaggaggg acttgagggc gtagagcttg 5460
ggggcgagga agacggactc gggggcgtag gcgtccgcgc cgcagctggc gcagacggtc 5520
tcgcactcca cgagccaggt gaggtcgggg cggtcggggt caaaaacgag gtttcctccg 5580
tgctttttga tgcgtttctt acctctggtc tccatgagct cgtgtccccg ctgggtgaca 5640
aagaggctgt ccgtgtcccc gtagaccgac tttatgggcc ggtcctcgag cggggtgccg 5700
cggtcctcgt cgtagaggaa ccccgcccac tccgagacga aggcccgggt ccaggccagc 5760
acgaaggagg ccacgtggga ggggtagcgg tcgttgtcca ccagcgggtc caccttctcc 5820
agggtatgca agcacatgtc cccctcgtcc acatccagga aggtgattgg cttgtaagtg 5880
taggccacgt gaccgggggt cccggccggg ggggtataaa agggggcggg cccctgctcg 5940
tcctcactgt cttccggatc gctgtccagg agcgccagct gttggggtag gtattccctc 6000
tcgaaggcgg gcatgacctc ggcactcagg ttgtcagttt ctagaaacga ggaggatttg 6060
atattgacgg tgccgttgga gacgcctttc atgagcccct cgtccatctg gtcagaaaag 6120
acgatctttt tgttgtcgag cttggtggcg aaggagccgt agagggcgtt ggagaggagc 6180
ttggcgatgg agcgcatggt ctggttcttt tccttgtcgg cgcgctcctt ggcggcgatg 6240
ttgagctgca cgtactcgcg cgccacgcac ttccattcgg ggaagacggt ggtgagctcg 6300
tcgggcacga ttctgacccg ccagccgcgg ttgtgcaggg tgatgaggtc cacgctggtg 6360
gccacctcgc cgcgcagggg ctcgttggtc cagcagaggc gcccgccctt gcgcgagcag 6420
aaggggggca gcgggtccag catgagctcg tctggggggt cggcgtccac ggtgaagatg 6480
ccgggcagga gctcggggtc gaagtagctg atggaagtgg ccagatcgtc cagggaagct 6540
tgccagtcgc gcacggccag cgcgcgctcg taggggctga ggggcgtgcc ccagggcatg 6600
gggtgcgtga gcgcggaggc gtacatgccg cagatgtcgt agacgtagag gggctcctcg 6660
aggatgccga tgtaggtggg gtagcagcgc cccccgcgga tgctggcgcg cacgtagtcg 6720
tacagctcgt gcgagggcgc gaggagcccc gtgccgagat tggagcgctg cggcttttcg 6780
gcgcggtaga cgatctggcg gaagatggcg tgggagttgg aggagatggt gggcctctgg 6840
aagatgttga agtgggcgtg gggcaggccg accgagtccc tgatgaagtg ggcgtaggag 6900
tcctgcagct tggcgacgag ctcggcggtg acgaggacgt ccagggcgca gtagtcgagg 6960
gtctcttgga tgatgtcata cttgagctgg cccttctgct tccacagctc gcggttgaga 7020
aggaactctt cgcggtcctt ccagtactct tcgaggggga acccgtcctg atcggcacgg 7080
taagagccca ccatgtagaa ctggttgacg gccttgtagg cgcagcagcc cttctccacg 7140
gggagggcgt aagcttgcgc ggccttgcgc agggaggtgt gggtgagggc gaaggtgtcg 7200
cgcaccatga ccttgaggaa ctggtgcttg aagtcgaggt cgtcgcagcc gccctgctcc 7260
cagagttgga agtccgtgcg cttcttgtag gcggggttgg gcaaagcgaa agtaacatcg 7320
ttgaagagga tcttgcccgc gcggggcatg aagttgcgag tgatgcggaa aggctggggc 7380
acctcggccc ggttgttgat gacctgggcg gcgaggacga tctcgtcgaa gccgttgatg 7440
ttgtgcccga cgatgtagag ttccacgaat cgcgggcggc ccttgacgtg gggcagcttc 7500
ttgagctcgt cgtaggtgag ctcggcgggg tcgctgagcc cgtgctgttc gagggcccag 7560
tcggcgacgt gggggttggc gctgaggaag gaagtccaga gatccacggc cagggcggtc 7620
tgcaagcggt cccggtactg acggaactgc tggcccacgg ccattttttc gggggtgacg 7680
cagtagaagg tgcgggggtc gccgtgccag cggtcccact tgagctggag ggcgaggtcg 7740
tgggcgagct cgacgagcgg tgggtccccg gagagtttca tgaccagcat gaaggggacg 7800
agctgcttgc cgaaggaccc catccaggtg taggtttcca catcgtaggt gaggaagagc 7860
ctttcggtgc gaggatgcga gccgatgggg aagaactgga tctcctgcca ccagttggag 7920
gaatggctgt tgatgtgatg gaagtagaaa tgccgacggc gcgccgagca ctcgtgcttg 7980
tgtttataca agcgtccgca gtgctcgcaa cgctgcacgg gatgcacgtg ctgcacgagc 8040
tgtacctgag ttcctttgac gaggaatttc agtgggcagt ggagcgctgg cggctgcatc 8100
tggtgctgta ctacgtcctg gccatcggcg tggccatcgt ctgcctcgat ggtggtcatg 8160
ctgacgaggc cgcgcgggag gcaggtccag acctcggctc ggacgggtcg gagagcgagg 8220
acgagggcgc gcaggccgga gctgtccagg gtcctgagac gctgcggagt caggtcagtg 8280
ggcagcggcg gcgcgcggtt gacttgcagg agcttttcca gggcgcgcgg gaggtccaga 8340
tggtacttga tctccacggc gccgttggtg gcgacgtcca cggcttgcag ggtcccgtgc 8400
ccctggggcg ccaccaccgt gccccgtttc ttcttgggcg ctggttccat gccggtcaga 8460
agcggcggcg aggacgcgcg ccgggcggca ggggcggctc ggggcccgga ggcaggggcg 8520
gcaggggcac gtcggcgccg cgcgcgggca ggttctggta ctgcgcccgg agaagactgg 8580
cgtgagcgac gacgcgacgg ttgacgtcct ggatctgacg cctctgggtg aaggccacgg 8640
gacccgtgag tttgaacctg aaagagagtt cgacagaatc aatctcggta tcgttgacgg 8700
cggcctgccg caggatctct tgcacgtcgc ccgagttgtc ctggtaggcg atctcggtca 8760
tgaactgctc gatctcctcc tcctgaaggt ctccgcggcc ggcgcgctcg acggtggccg 8820
cgaggtcgtt ggagatgcgg cccatgagct gcgagaaggc gttcatgccg gcctcgttcc 8880
agacgcggct gtagaccacg gctccgtcgg ggtcgcgcgc gcgcatgacc acctgggcga 8940
ggttgagctc gacgtggcgc gtgaagaccg cgtagttgca gaggcgctgg tagaggtagt 9000
tgagcgtggt ggcgatgtgc tcggtgacga agaagtacat gatccagcgg cggagcggca 9060
tctcgctgac gtcgcccagg gcttccaagc gctccatggc ctcgtagaag tccacggcga 9120
agttgaaaaa ctgggagttg cgcgccgaga cggtcaactc ctcctccaga agacggatga 9180
gctcggcgat ggtggcgcgc acctcgcgct cgaaggcccc ggggggctcc tcttcttcca 9240
tctcctcctc ctcttcctcc tccactaaca tctcttctac ttcctcctca ggaggcggtg 9300
gcgggggagg ggccctgcgt cgccggcggc gcacgggcag acggtcgatg aagcgctcga 9360
tggtctcccc gcgccggcga cgcatggtct cggtgacggc gcgcccgtcc tcgcggggcc 9420
gcagcgtgaa gacgccgccg cgcatctcca ggtggccgcc gggggggtct ccgttgggca 9480
gggagagggc gctgacgatg catcttatca attggcccgt agggactccg cgcaaggacc 9540
tgagcgtctc gagatccacg ggatccgaaa accgctgaac gaaggcttcg agccagtcgc 9600
agtcgcaagg taggctgagc ccggtttctt cgggtatttg gtcgggaggc gggcgggcga 9660
tgctgctggt gatgaagttg aagtaggcgg tcctgagacg gcggatggtg gcgaggagca 9720
ccaggtcctt gggcccggct tgctggatgc gcagacggtc ggccatgccc caggcgtggt 9780
cctgacacct ggcgaggtcc ttgtagtagt cctgcatgag ccgctccacg ggcacctcct 9840
cctcgcccgc gcggccgtgc atgcgcgtga gcccgaaccc gcgctgcggc tggacgagcg 9900
ccaggtcggc gacgacgcgc tcggcgagga tggcctgctg gatctgggtg agggtggtct 9960
ggaagtcgtc gaagtcgacg aagcggtggt aggctccggt gttgatggtg tatgagcagt 10020
tggccatgac ggaccagttg acggtctggt ggccggggcg cacgagctcg tggtacttga 10080
ggcgcgagta ggcgcgcgtg tcgaagatgt agtcgttgca ggtgcgcacg aggtactggt 10140
atccgacgag gaagtgcggc ggcggctggc ggtagagcgg ccatcgctcg gtggcggggg 10200
cgccgggcgc gaggtcctcg agcatgaggc ggtggtagcc gtagatgtac ctggacatcc 10260
aggtgatgcc ggcggcggtg gtggaggcgc gcgggaactc gcggacgcgg ttccagatgt 10320
tgcgcagcgg caggaagtag ttcatggtgg ccgcggtctg gcccgtgagg cgcgcgcagt 10380
cgtggatgct ctatacgggc aaaaacgaaa gcggtcagcg gctcgactcc gtggcctgga 10440
ggctaagcga acgggttggg ctgcgcgtgt accccggttc gaatctcgaa tcaggctgga 10500
gccgcagcta acgtggtact ggcactcccg tctcgaccca agcctgcaca aaacctccag 10560
gatacggagg cgggtcgttt tgcaactttt tgaggccgga aatgaaacta gtaagcgcga 10620
aaagcggccg accgcgatgg ctcgctgccg tagtctggag aagaatcgcc agggttgcgt 10680
tgcggtgtgc cccggttcga ggccggccgg attccgcggc taacgagggc gtggctgccc 10740
cgtcgtttcc aagaccccta gccagccgac ttctccagtt acggagcgag cccctctttt 10800
gttttgtttg tttttgccag atgcatcccg tactgcggca gatgcgcccc caccaccctc 10860
caccgcaaca acagcccact ccacagccgg cgcttctgcc cccgccccag cagcagcaac 10920
ttccagccac gaccgccgcg gccgccgtga gcggggctgg acagacttct cagtatgacc 10980
acctggcctt ggaagagggc gaggggctgg cgcgcctggg ggcgtcgtcg ccggagcggc 11040
acccgcgcgt gcagatgaaa cgggacgctc gcgaggccta cgtgcccaag cagaacctgt 11100
tcagagacag gagcggcgag gagcccgagg agatgcgcgc ggcccggttc cacgcggggc 11160
gggagctgcg gcgcggcctg gaccgaaaga gggtgctgag ggacgaggat ttcgaggcgg 11220
acgagctgac ggggatcagc cccgcgcgcg cgcacgtggc cgcggccaac ctggtcacgg 11280
cgtacgagca gaccgtgaag gaggagagca acttccaaaa atccttcaac aaccacgtgc 11340
gcaccctgat cgcgcgcgag gaggtgaccc tgggcctgat gcacctgtgg gacctgctgg 11400
aggccatcgt gcagaacccc accagcaagc cgctgacggc gcagctgttc ctggtggtgc 11460
agcacagtcg ggacaacgag gcgttcaggg aggcgctgct gaatatcacc gagcccgagg 11520
gccgctggct cctggacctg gtgaacattc tgcagagcat cgtggtgcag gagcgcgggc 11580
tgccgctgtc cgagaagctg gcggccatca acttctcggt gctgagtctg ggcaagtact 11640
acgctaggaa gatctacaag accccgtacg tgcccataga caaggaggtg aagatcgacg 11700
ggttttacat gcgcatgacc ctgaaagtgc tgaccctgag cgacgatctg ggggtgtacc 11760
gcaacgacag gatgcaccgc gcggtgagcg ccagccgccg gcgcgagctg agcgaccagg 11820
agctgatgca cagcctgcag cgggccctga ccggggccgg gaccgagggg gagagctact 11880
ttgacatggg cgcggacctg cgctggcagc ccagccgccg ggccttggaa gctgccggcg 11940
gttcccccta cgtggaggag gtggacgatg aggaggagga gggcgagtac ctggaagact 12000
gatggcgcga ccgtattttt gctagatgca gcaacagcca ccgccgcctc ctgatcccgc 12060
gatgcgggcg gcgctgcaga gccagccgtc cggcattaac tcctcggacg attggaccca 12120
ggccatgcaa cgcatcatgg cgctgacgac ccgcaatccc gaagccttta gacagcagcc 12180
tcaggccaac cggctctcgg ccatcctgga ggccgtggtg ccctcgcgct cgaaccccac 12240
gcacgagaag gtgctggcca tcgtgaacgc gctggtggag aacaaggcca tccgcggcga 12300
cgaggccggg ctggtgtaca acgcgctgct ggagcgcgtg gcccgctaca acagcaccaa 12360
cgtgcagacg aacctggacc gcatggtgac cgacgtgcgc gaggcggtgt cgcagcgcga 12420
gcggttccac cgcgagtcga acctgggctc catggtggcg ctgaacgcct tcctgagcac 12480
gcagcccgcc aacgtgcccc ggggccagga ggactacacc aacttcatca gcgcgctgcg 12540
gctgatggtg gccgaggtgc cccagagcga ggtgtaccag tcggggccgg actacttctt 12600
ccagaccagt cgccagggct tgcagaccgt gaacctgagc caggctttca agaacttgca 12660
gggactgtgg ggcgtgcagg ccccggtcgg ggaccgcgcg acggtgtcga gcctgctgac 12720
gccgaactcg cgcctgctgc tgctgctggt ggcgcccttc acggacagcg gcagcgtgag 12780
ccgcgactcg tacctgggct acctgcttaa cctgtaccgc gaggccatcg ggcaggcgca 12840
cgtggacgag cagacctacc aggagatcac ccacgtgagc cgcgcgctgg gccaggagga 12900
cccgggcaac ctggaggcca ccctgaactt cctgctgacc aaccggtcgc agaagatccc 12960
gccccagtac gcgctgagca ccgaggagga gcgcatcctg cgctacgtgc agcagagcgt 13020
ggggctgttc ctgatgcagg agggggccac gcccagcgcc gcgctcgaca tgaccgcgcg 13080
caacatggag cccagcatgt acgcccgcaa ccgcccgttc atcaataagc tgatggacta 13140
cttgcatcgg gcggccgcca tgaactcgga ctactttacc aacgccatct tgaacccgca 13200
ctggctcccg ccgcccgggt tctacacggg cgagtatgac atgcccgacc ccaacgacgg 13260
gttcctgtgg gatgacgtgg acagcagcgt gttctcgccg cgccccgcca ccaccgtgtg 13320
gaagaaagag ggcggggacc ggcggccgtc ctcggcgctg tccggtcgcg cgggtgctgc 13380
cgcggcggtg cccgaggccg ccagcccctt cccgagcctg cccttttcgc tgaacagcgt 13440
gcgcagcagc gagctgggac ggctgacgcg gccgcgcctg ctgggcgagg aggagtacct 13500
gaacgactcc ttgttgaggc ccgagcgcga gaagaacttc cccaataacg ggatagagag 13560
cctggtggac aagatgagcc gctggaagac gtacgcgcac gagcacaggg acgagccgcg 13620
agctagcagc agcaccggcg cccgtagacg ccagcggcac gacaggcagc ggggactggt 13680
gtgggacgat gaggattccg ccgacgacag cagcgtgttg gacttgggtg ggagtggtgg 13740
tggtaacccg ttcgctcacc tgcgcccccg tatcgggcgc ctgatgtaag aatctgaaaa 13800
aataaaaaac ggtactcacc aaggccatgg cgaccagcgt gcgttcttct ctgttgtttg 13860
tagtagtatg atgaggcgcg tgtacccgga gggtcctcct ccctcgtacg agagcgtgat 13920
gcagcaggcg gtggcggcgg cgatgcagcc cccgctggag gcgccttacg tgcccccgcg 13980
gtacctggcg cctacggagg ggcggaacag cattcgttac tcggagctgg cacccttgta 14040
cgataccacc cggttgtacc tggtggacaa caagtcggcg gacatcgcct cgctgaacta 14100
ccagaacgac cacagcaact tcctgaccac cgtggtgcag aacaacgatt tcacccccac 14160
ggaggccagc acccagacca tcaactttga cgagcgctcg cggtggggcg gccagctgaa 14220
aaccatcatg cacaccaaca tgcccaacgt gaacgagttc atgtacagca acaagttcaa 14280
ggcgcgggtc atggtctcgc gcaagacccc caacggggtc gcggtagggg atgattatga 14340
tggtagtcag gacgagctga cctacgagtg ggtggagttt gagctgcccg agggcaactt 14400
ctcggtgacc atgaccatcg atctgatgaa caacgccatc atcgacaatt acttggcggt 14460
gggacggcag aacggggtgc tggagagcga catcggcgtg aagttcgaca cgcgcaactt 14520
ccggctgggc tgggaccccg tgaccgagct ggtgatgccg ggcgtgtaca ccaacgaggc 14580
cttccacccc gacatcgtcc tgctgcccgg ctgcggcgtg gacttcaccg agagccgcct 14640
cagcaacctg ctgggcatcc gcaagcggca gcccttccag gagggcttcc agatcctgta 14700
cgaggacctg gaggggggca acatccccgc gctcttggat gtcgaagcct atgaagaaag 14760
taaggaaaaa gcagaggctg aggcaactgc agccgtggct actgccgctg tcaccgatgc 14820
agatgcagct actaccaggg gcgatacatt cgccactgtg gctgaagaag cagccgccgt 14880
agcggcgacc gatgatagtg aaagtaagat agtcatcaag ccggtggaga aggacagcaa 14940
gaacaggagc tacaacgttc tatcggatgg aaagaacacc gcctaccgca gctggtacct 15000
ggcctacaac tacggcgacc ccgagaaggg cgtgcgctcc tggacgctgc tcaccacctc 15060
ggacgtcacc tgcggcgtgg agcaagtcta ctggtcgctg cccgacatga tgcaagaccc 15120
ggtcaccttc cgctccacgc gtcaagttag caactacccg gtggtgggcg ccgagctcct 15180
gcccgtctac tccaagagct tcttcaacga gcaggccgtc tactcgcagc agctgcgcgc 15240
cttcacctcg ctcacgcacg tcttcaaccg cttccccgag aaccagatcc tcgtccgccc 15300
gcccgcgccc accattacca ccgtcagtga aaacgttcct gctctcacag atcacgggac 15360
cctgccgctg cgcagcagta tccggggagt ccagcgcgtg accgtcactg acgccagacg 15420
ccgcacctgc ccctacgtct acaaggccct gggcgtagtc gcgccgcgcg tcctctcgag 15480
ccgcaccttc taaaaaatgt ccattctcat ctcgcccagt aataacaccg gttggggcct 15540
gcgcgcgccc agcaagatgt acggaggcgc tcgccaacgc tccacgcaac accccgtgcg 15600
cgtgcgcggg cacttccgcg ctccctgggg cgccctcaag ggccgcgtgc gctcgcgcac 15660
caccgtcgac gacgtgatcg accaggtggt ggccgacgcg cgcaactaca cgcccgccgc 15720
cgcgcccgtc tccaccgtgg acgccgtcat cgacagcgtg gtggccgacg cgcgccggta 15780
cgcccgcgcc aagagccggc ggcggcgcat cgcccggcgg caccggagca cccccgccat 15840
gcgcgcggcg cgagccttgc tgcgcagggc caggcgcacg ggacgcaggg ccatgctcag 15900
ggcggccaga cgcgcggcct ctggcagcag cagcgccggc aggacccgca gacgcgcggc 15960
cacggcggcg gcggcggcca tcgccagcat gtcccgcccg cggcgcggca acgtgtactg 16020
ggtgcgcgac gccgccaccg gtgtgcgcgt gcccgtgcgc acccgccccc ctcgcacttg 16080
aagatgctga cttcgcgatg ttgatgtgtc ccagcggcga ggaggatgtc caagcgcaaa 16140
ttcaaggaag agatgctcca ggtcatcgcg cctgagatct acggccccgc ggcggcggtg 16200
aaggaggaaa gaaagccccg caaactgaag cgggtcaaaa aggacaaaaa ggaggaggaa 16260
gatgtggacg gactggtgga gtttgtgcgc gagttcgccc cccggcggcg cgtgcagtgg 16320
cgcgggcgga aagtgaaacc ggtgctgcga cccggcacca ccgtggtctt cacgcccggc 16380
gagcgttccg gctccgcctc caagcgctcc tacgacgagg tgtacgggga cgaggacatc 16440
ctcgagcagg cggccgagcg tctgggcgag tttgcttacg gcaagcgcag ccgccccgcg 16500
cccttgaaag aggaggcggt gtccatcccg ctggaccacg gcaaccccac gccgagtctg 16560
aagccggtga ccctgcagca ggtgctgccg agcgcggcgc cgcgccgggg cttcaagcgc 16620
gagggcggcg aggatctgta cccgaccatg cagctgatgg tgcccaagcg ccagaagctg 16680
gaggacgtgc tggagcacat gaaggtggac cccgaggtgc agcccgaggt caaggtgcgg 16740
cccatcaagc aggtggcccc gggcctgggc gtgcagaccg tggacatcaa gatccccacg 16800
gagcccatgg aaacgcagac cgagcccgtg aagcccagca ccagcaccat ggaggtgcag 16860
acggatccct ggatgccggc gccggcttcc accaccacca ctcgccgaag acgcaagtac 16920
ggcgcggcca gcctgctgat gcccaactac gcgctgcatc cttccatcat ccccacgccg 16980
ggctaccgcg gcacgcgctt ctaccgcggc tacagcagcc gccgcaagac caccacccgc 17040
cgccgccgtc gtcgcacccg ccgcagcagc accgcgactt ccgccgcctt ggtgcggaga 17100
gtgtaccgca gcgggcgcga gcctctgacc ctgccgcgcg cgcgctacca cccgagcatc 17160
gccatttaac tctgccgtcg cctcctactt gcagatatgg ccctcacatg ccgcctccgc 17220
gtccccatta cgggctaccg aggaagaaag ccgcgccgta gaaggctgac ggggaacggg 17280
ctgcgtcgcc atcaccaccg gcggcggcgc gccatcagca agcggttggg gggaggcttc 17340
ctgcccgcgc tgatccccat catcgccgcg gcgatcgggg cgatccccgg catagcttcc 17400
gtggcggtgc aggcctctca gcgccactga gacacagctt ggaaaatttg taataaaaaa 17460
tggactgacg ctcctggtcc tgtgatgtgt gtttttagat ggaagacatc aatttttcgt 17520
ccctggcacc gcgacacggc acgcggccgt ttatgggcac ctggagcgac atcggcaaca 17580
gccaactgaa cgggggcgcc ttcaattgga gcagtctctg gagcgggctt aagaatttcg 17640
ggtccacgct caaaacctat ggcaacaagg cgtggaacag cagcacaggg caggcgctga 17700
gggaaaagct gaaagagcag aacttccagc agaaggtggt cgatggcctg gcctcgggca 17760
tcaacggggt ggtggacctg gccaaccagg ccgtgcagaa acagatcaac agccgcctgg 17820
acgcggtccc gcccgcgggg tccgtggaga tgccccaggt ggaggaggag ctgcctcccc 17880
tggacaagcg cggcgacaag cgaccgcgtc ccgatgcaga ggagacgctg ctgacgcaca 17940
cggacgagcc gcccccgtac gaggaggcgg tgaaactggg tctgcccacc acgcggcccg 18000
tggcgcctct ggccaccggg gtgctgaaac ccagcagcag cagccagccc gcgaccctgg 18060
acttgcctcc gcctgcttcc cgcccctcca cagtggctaa gcccctgccg ccggtggccg 18120
tcgcgtcgcg cgccccccga ggccgccccc aggcgaactg gcagagcact ctgaacagca 18180
tcgtgggtct gggagtgcag agtgtgaagc gccgccgctg ctattaaaag acactgtagc 18240
gcttaacttg cttgtctgtg tgtatatgta tgtccgccga ccagaaggaa gaggcgcgtc 18300
gccgagttgc aagatggcca ccccatcgat gctgccccag tgggcgtaca tgcacatcgc 18360
cggacaggac gcttcggagt acctgagtcc gggtctggtg cagttcgccc gcgccacaga 18420
cacctacttc agtctgggga acaagtttag gaaccccacg gtggcgccca cgcacgatgt 18480
gaccaccgac cgcagccagc ggctgacgct gcgcttcgtg cccgtggacc gcgaggacaa 18540
cacctactcg tacaaagtgc gctacacgct ggccgtgggc gacaaccgcg tgctggacat 18600
ggccagcacc tactttgaca tccgcggcgt gctggatcgg ggccccagct tcaaacccta 18660
ctccggcacc gcctacaaca gcctggctcc caagggagcg cccaacacct cacagtggat 18720
aaccaaagac aatggaactg ataagacata cagttttgga aatgctccag tcagaggatt 18780
ggacattaca gaagagggtc tccaaatagg acccgatgag tcagggggtg aaagcaagaa 18840
aatttttgca gacaaaacct atcagcctga acctcagctt ggagatgagg aatggcatga 18900
tactattgga gctgaagaca agtatggagg cagagcgctt aaacctgcca ccaacatgaa 18960
accctgctat gggtctttcg ccaagccaac taatgctaag ggaggtcagg ctaaaagcag 19020
aaccaaggac gatggcacta ctgagcctga tattgacatg gccttctttg acgatcgcag 19080
tcagcaagct agtttcagtc cagaacttgt tttgtatact gagaatgtcg atctggacac 19140
cccggatacc cacattattt acaaacctgg cactgatgaa acaagttctt ctttcaactt 19200
gggtcagcag tccatgccca acagacccaa ctacatcggc ttcagagaca actttatcgg 19260
tctcatgtac tacaacagta ctggcaatat gggtgtacta gctggacagg cctcccagct 19320
gaatgctgtg gtggacttgc aggacagaaa cactgaactg tcctaccagc tcttgcttga 19380
ctctctgggt gacagaacca ggtatttcag tatgtggaac caggcggtgg acagctacga 19440
ccccgatgtg cgcattattg aaaatcacgg tgtggaggat gaactaccca actattgctt 19500
ccctttgaat ggtgtgggct ttacagatac attccaggga attaaggtta aaactaccaa 19560
taacggaaca gcaaatgcta cagagtggga atctgatacc tctgtcaata atgctaatga 19620
gattgccaag ggcaatcctt tcgccatgga gatcaacatc caggccaacc tgtggcggaa 19680
cttcctctac gcgaacgtgg cgctgtacct gcccgactcc tacaagtaca cgccggccaa 19740
catcacgctg cccgccaaca ccaacaccta cgattacatg aacggccgcg tggtagcgcc 19800
ctcgctggtg gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggacaa 19860
cgtcaacccc ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg 19920
caacgggcgc tacgtgccct tccacatcca ggtgccccaa aagtttttcg ccatcaagag 19980
cctcctgctc ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat 20040
gatcctgcag agctccctcg gcaacgacct gcgcacggac ggggcctcca tcgccttcac 20100
cagcatcaac ctctacgcca ccttcttccc catggcgcac aacaccgcct ccacgctcga 20160
ggccatgctg cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa 20220
catgctctac cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa 20280
ctgggccgcc ttccgcggct ggtccttcac gcgcctcaag acccgcgaga cgccctcgct 20340
cggctccggg ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac 20400
cttctacctc aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg 20460
gcccggcaac gaccgcctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg 20520
agaggggtac aacgtggccc agtgcaacat gaccaaggac tggttcctgg ttcagatgct 20580
ggcccactac aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat 20640
gtactccttc ttccgcaact tccagcccat gagccgccag gtcgtggacg aggtcaacta 20700
caaggactac caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta 20760
cctcgcgccc accatgcgcc agggacagcc ctaccccgcc aactacccct acccgctcat 20820
cggcaagagc gccgtcgcca gcgtcaccca gaaaaagttc ctctgcgacc gggtcatgtg 20880
gcgcatcccc ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa 20940
catgctctac gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga 21000
tgagtccacc cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc 21060
ccaccgcggc gtcatcgagg ccgtctacct gcgcacgccc ttctcggccg gtaacgccac 21120
cacctaagcc ccgctcttgc ttcttgcaag atgacggcct gtgcgggctc cggcgagcag 21180
gagctcaggg ccatcctccg cgacctgggc tgcgggccct gcttcctggg caccttcgac 21240
aagcgcttcc cgggattcat ggccccgcac aagctggcct gcgccatcgt caacacggcc 21300
ggccgcgaga ccgggggcga gcactggctg gccttcgcct ggaacccgcg ctcccacacc 21360
tgctacctct tcgacccctt cgggttctcg aacgagcgcc tcaagcagat ctaccagttc 21420
gagtacgagg gcctgctgcg ccgcagcgcc ctggccaccg aggaccgctg cgtcaccctg 21480
gaaaagtcca cccagaccgt gcagggtccg cgctcggccg cctgcgggct cttctgctgc 21540
atgttcctgc acgccttcgt gcactggccc gaccgcccca tggacaagaa ccccaccatg 21600
aacttgctga cgggggtgcc caacggcatg ctccagtcgc cccaggtgga acccaccctg 21660
cgccgcaacc aggaagcgct ctaccgcttc ctcaacgccc actccgccta ctttcgctcc 21720
caccgcgcgc gcatcgagaa ggccaccgcc ttcgaccgca tgaatcaaga catgtaaacc 21780
gtgtgtgtat gtgaatgctt tattcataat aaacagcaca tgtttatgcc accttctctg 21840
aggctctgac tttatttaga aatcgaaggg gttctgccgg ctctcggcat gccccgcggg 21900
cagggatacg ttgcggaact ggtacttggg cagccacttg aactcgggga tcagcagctt 21960
gggcacgggg aggtcgggga acgagtcgct ccacagcttg cgcgtgagtt gcagggcgcc 22020
cagcaggtcg ggcgcggaga tcttgaaatc gcagttggga cccgcgttct gcgcgcgaga 22080
gttgcggtac acggggttgc agcactggaa caccatcagg gccgggtgct tcacgctcgc 22140
cagcaccgtc gcgtcggtga tgccctccac gtccagatcc tcggcgttgg ccatcccgaa 22200
gggggtcatc ttgcaggtct gccgccccat gctgggcacg cagccgggct tgtggttgca 22260
atcgcagtgc agggggatca gcatcatctg ggcctgctcg gagctcatgc ccgggtacat 22320
ggccttcatg aaagcctcca gctggcggaa ggcctgctgc gccttgccgc cctcggtgaa 22380
gaagaccccg caggacttgc tagagaactg gttggtggcg cagcccgcgt cgtgcacgca 22440
gcagcgcgcg tcgttgttgg ccagctgcac cacgctgcgc ccccagcggt tctgggtgat 22500
cttggcccgg tcggggttct ccttcagcgc gcgctgtccg ttctcgctcg ccacatccat 22560
ctcgatcgtg tgctccttct ggatcatcac ggtcccgtgc aggcaccgca gcttgctctc 22620
ggcctcggtg cacccgtgca gccacagcgc gcagccggtg ctctcccagt tcttgtgggc 22680
gatctgggag tgcgagtgca cgaagccctg caggaagcgg cccatcatcg cggtcagggt 22740
cttgttgctg gtgaaggtca gcgggatgcc gcggtgctcc tcgttcacat acaggtggca 22800
gatgcggcgg tacacctcgc cctgctcggg catcagctgg aaggcggact tcaggtcgct 22860
ctccacgcgg taccggtcca tcagcagcgt catgacttcc atgcccttct cccaggccga 22920
aacgatcggc aggctcaggg ggttcttcac cgttgtcatc ttagtcgccg ccgccgaggt 22980
cagggggtcg ttctcgtcca gggtctcaaa cactcgcttg ccgtccttct cgatgatgcg 23040
cacggggggg aagctgaagc ccacggccgc cagctcctcc tcggcctgcc tttcgtcctc 23100
gctgtcctgg ctgatgtctt gcaaaggcac atgcttggtc ttgcggggtt tctttttggg 23160
cggcagaggc ggcggcggag acgtgctggg cgagcgcgag ttctcgctca ccacgactat 23220
ttcttcttct tggccgtcgt ccgagaccac gcggcggtag gcatgcctct tctggggcag 23280
aggcggaggc gacgggctct cgcggttcgg cgggcggctg gcagagcccc ttccgcgttc 23340
gggggtgcgc tcctggcggc gctgctctga ctgacttcct ccgcggccgg ccattgtgtt 23400
ctcctaggga gcaacaacaa gcatggagac tcagccatcg tcgccaacat cgccatctgc 23460
ccccgccgcc gacgagaacc agcagaatga aagcttaacc gccccgccgc ccagccccac 23520
ctccgacgcc gcggccccag acatgcaaga gatggaggaa tccatcgaga ttgacctggg 23580
ctacgtgacg cccgcggagc acgaggagga gctggcagcg cgcttttcag ccccggaaga 23640
gaaccaccaa gagcagccag agcaggaagc agagagcgag cagaaccagg ctgggctcga 23700
gcatggcgac tacctgagcg gggcagagga cgtgctcatc aagcatctga cccgccaatg 23760
catcatcgtc aaggacgcgc tgctcgaccg cgccgaggtg cccctcagcg tggcggagct 23820
cagccgcgcc tacgagcgca acctcttctc gccgcgcgtg ccccccaagc gccagcccaa 23880
cggcacctgc gagcccaacc cgcgcctcaa cttctacccg gtcttcgcgg tgcccgaggc 23940
cctggccacc taccacctct ttttcaagaa ccaaaggatc cccgtctcct gccgcgccaa 24000
ccgcacccgc gccgacgccc tgctcaacct gggccccggc gcccgcctac ctgatatcac 24060
ctccttggaa gaggttccca agatcttcga gggtctgggc agcgacgaga ctcgggccgc 24120
gaacgctctg caaggaagcg gagaggaaca tgagcaccac agcgccctgg tggagttgga 24180
aggcgacaac gcgcgcctgg cggtgctcaa gcgcacggtc gagctgaccc acttcgccta 24240
cccggcgctc aacctgcccc ccaaggtcat gagcgccgtc atggaccagg tgctcatcaa 24300
gcgcgcctcg cccattgagg acatgcagga ccccgagagc tcggacgagg gcaagcccgt 24360
ggtcagcgac gagcagctgg cgcgctggct gggagcgagt agcacccccc agagcctgga 24420
agagcggcgc aagctcatga tggccgtggt cctggtgacc gtggagctgg agtgtctgcg 24480
ccgcttcttc gccgacgcag agaccctgcg caaggtcgag gagaacctgc actacctctt 24540
caggcacggg ttcgtgcgcc aggcctgcaa gatctccaac gtggagctga ccaacctggt 24600
ctcctacatg ggcatcctgc acgagaaccg cctggggcag aacgtgctgc acaccaccct 24660
gcgcggggag gcccgccgcg actacatccg cgactgcgtc tacctgtacc tctgccacac 24720
ctggcagacg ggcatgggcg tgtggcagca gtgcctggag gagcagaacc tgaaagagct 24780
ctgcaagctc ctgcagaaga acctcaaggc cctgtggacc gggttcgacg agcgcaccac 24840
cgcctcggac ctggccgacc tcatcttccc cgagcgcctg cggctgacgc tgcgcaacgg 24900
gctgcccgac tttatgagcc aaagcatgtt gcaaaacttt cgctctttca tcctcgaacg 24960
ctccgggatc ctgcccgcca cctgctccgc gctgccctcg gacttcgtgc cgctgacctt 25020
ccgcgagtgc cccccgccgc tctggagcca ctgctacttg ctgcgcctgg ccaactacct 25080
ggcctaccac tcggacgtga tcgaggacgt cagcggcgag ggtctgctgg agtgccactg 25140
ccgctgcaac ctctgcacgc cgcaccgctc cctggcctgc aacccccagc tgctgagcga 25200
gacccagatc atcggcacct tcgagttgca aggccccggc gaggagggca aggggggtct 25260
gaaactcacc ccggggctgt ggacctcggc ctacttgcgc aagttcgtgc ccgaggacta 25320
ccatcccttc gagatcaggt tctacgagga ccaatcccag ccgcccaagg ccgagctgtc 25380
ggcctgcgtc atcacccagg gggccatcct ggcccaattg caagccatcc agaaatcccg 25440
ccaagaattt ctgctgaaaa agggccacgg ggtctacttg gacccccaga ccggagagga 25500
gctcaacccc agcttccccc aggatgcccc gaggaagcag caagaagctg aaagtggagc 25560
tgccgccgcc ggaggatttg gaggaagact gggagagcag tcaggcagag gaggagatgg 25620
aagactggga cagcactcag gcagaggagg acagcctgca agacagtctg gaggaggaag 25680
acgaggtgga ggaggaggag gcagaggaag aagcagccgc cgccagaccg tcgtcctcgg 25740
cggagaaagc aagcagcacg gataccatct ccgctccggg tcggggtcgc ggcggccggg 25800
cccacagtag gtgggacgag accgggcgct tcccgaaccc caccacccag accggtaaga 25860
aggagcggca gggatacaag tcctggcggg ggcacaaaaa cgccatcgtc tcctgcttgc 25920
aagcctgcgg gggcaacatc tccttcaccc ggcgctacct gctcttccac cgcggggtga 25980
acttcccccg caacatcttg cattactacc gtcacctcca cagcccctac tactgtttcc 26040
aagaagaggc agaaacccag cagcagcaga aaaccagcga cagcggcagc agctagaaaa 26100
tccacagcgg caggtggact gaggatcgcg gcgaacgagc cggcgcagac ccgggagctg 26160
aggaaccgga tctttcccac cctctatgcc atcttccagc agagtcgggg gcaggagcag 26220
gaactgaaag tcaagaaccg ttctctgcgc tcgctcaccc gcagttgtct gtatcacaag 26280
agcgaagacc aacttcagcg cactctcgag gacgccgagg ctctcttcaa caagtactgc 26340
gcgctcactc ttaaagagta gcccgcgccc gcccacacac ggaaaaaggc gggaattacg 26400
tcaccacctg cgcccttcgc ccgaccatca tcatgagcaa agagattccc acgccttaca 26460
tgtggagcta ccagccccag atgggtctgg ccgccggcgc cgcccaggac tactccaccc 26520
gcatgaactg gctcagtgcc gggcccgcga tgatctcacg ggtgaatgac atccgcgccc 26580
atcgaaacca gatactccta gaacagtcag cgatcaccgc cacgccccgc catcacctta 26640
atccgcgtaa ttggcccgcc gccctggtgt accaggaaat tccccagccc acgaccgtac 26700
tacttccgcg agacgcccag gccgaagtcc agctgactaa ctcaggtgtc cagctggccg 26760
gcggcgccgc cctgtgtcgt caccgccccg ctcagggtat aaagcggctg gtgatccgag 26820
gcagaggcac acagctcaac gacgaggtgg tgagctcttc gctgggtctg cgacctgacg 26880
gagtcttcca actcgccgga tcggggagat cttccttcac gcctcgtcag gccgtcctga 26940
ctttggagag ttcgtcctcg cagccccgct cgggcggcat cggcactctc cagttcgtgg 27000
aggagttcac tccctcggtc tacttcaacc ccttctccgg ctcccccggc cactacccgg 27060
acgagttcat cccgaacttc gacgccatca gcgagtcggt ggacggctac gattgaatgt 27120
cccatggtgg cgcagctgac ctagctcggc ttcgacacct ggaccactgc cgccgcttcc 27180
gctgcttcgc tcgggatctc gccgagtttg cctactttga gctgcccgag gagcaccctc 27240
agggcccggc ccacggagtg cggatcatca tcgaaggggg cctcgactcc cacctgcttc 27300
ggatcttcag ccagcgaccg atcctggtcg agcgcgagca aggacagacc cgtctgaccc 27360
tgtactgcat ctgcaaccac cccggcctgc atgaaagtct ttgttgtctg ctgtgtactg 27420
agtataataa aagctgagat cagcgactac tccggactcg attgtggtgt tcctgctatc 27480
aaccggtccc tgttcttcac cgggaacgag accgagctcc agctccagtg taagccccac 27540
aagaagtacc tcacctggct gttccagggc tctccgatcg ccgttgtcaa ccactgcgac 27600
aacgacggag tcctgctgag cggccctgcc aaccttactt tttccacccg cagaagcaag 27660
ctccagctct tccaaccctt cctccccggg acctatcagt gcgtctcggg accctgccat 27720
cacaccttcc acctgatccc gaataccaca gcgccgctcc ccgctactaa caaccaaact 27780
acccaccaac gccaccgtcg cgacctttcc tctgaatcta atactaccac ccacaccgga 27840
ggtgagctcc gaggtcgacc aacctctggg atttactacg gcccctggga ggtggtgggg 27900
ttaatagcgc taggcctagt tgtgggtggg cttttggctc tctgctacct atacctccct 27960
tgctgttcgt acttagtggt gctgtgttgc tggtttaaga aatggggaag atcaccctag 28020
tgagctgcgg tgtgctggtg gcggtgttgc tttcgattgt gggactgggc ggcgcggctg 28080
tagtgaagga ggagaaggcc gatccctgct tgcatttcaa tcccgacaaa tgccagctga 28140
gttttcagcc cgatggcaat cggtgcacgg tgctgatcaa gtgcggatgg gaatgtgaga 28200
acgtgagaat cgagtacaat aacaagactc ggaacaatac tctcgcgtcc gtgtggcaac 28260
ccggggaccc cgagtggtac accgtctctg tccccggtgc tgacggctcc ccgcgcaccg 28320
tgaataatac tttcattttt gcgcacatgt gcgacacggt catgtggatg agcaagcagt 28380
acgatatgtg gccccccacg aaggagaaca tcgtggtctt ctccatcgct tacagcgtgt 28440
gcacggcgct aatcaccgct atcgtgtgcc tgagcattca catgctcatc gctattcgcc 28500
ccagaaataa tgccgaaaaa gagaaacagc cataacacgt tttttcacac acctttttca 28560
gaccatggcc tctgttactg ccctaattat ttttttgggt ctcgtgggca ctagcagcac 28620
ttttcagcat ataaacaaaa ctgtttatgc tggttctaat tctgtattac ctgggcatca 28680
atcacaccag aaagtttcat ggtactggta tgataaaaat aacacgccag tcacactctg 28740
caagggtcat caaacaccca taaaccgtag tggaattttt tttaaatgta atcataataa 28800
tattacacta ctttcaatta caaagcacta ttctggtact tactatggaa ccaattttaa 28860
cataaaacag gacacttact atagtgtcac agtattggat ccaactactc ctagaacaac 28920
tacaaaaccc acaactacta agaggcacac taaacctaaa actaccaaga aaaccactgt 28980
caaaacaaca actaggacca ccacaactac agaggctacc accagcacaa cacttgctgc 29040
aactacacac acacacactg agctaacctt acagaccact aatgatttga tagccctgtt 29100
gcaaaagggg gataacagca ccacttccga tgaggaaata cccaaatcca tgattggcat 29160
tattgttgct gtagtggtgt gcatgttgat catcgccttg tgcatggtgt actatgcctt 29220
ctgctacaga aagcacagac tgaacgacaa gctggaacac ttactaagtg ttgaatttta 29280
attttttaga accatgaaga tcctaggcct tttagttttt tctatcatta cctctgctct 29340
ttgtgaatca gtgaataaag atgttactat taccactggt tctaattata cactgaaagg 29400
gccaccctca ggtatgcttt cgtggtattg ctattttgga actgacactg atcaaactga 29460
attatgcaat tttcaaaaag gcaaaacctc aaactctaaa atctctaatt atcaatgcaa 29520
tggcactgat ctgatactac tcaatgtcac gaaagcatat ggtggcagtt attcttgccc 29580
tggacaaaac actgaagaaa tgatttttta caaagtggaa gtggttgatc ccactactcc 29640
acccaccacc acaactactc acaccacaca cacagaacaa accacagcag aggaggcagc 29700
aaagttagcc ttgcaggtcc aagacagttc atttgttggc attaccccta cacctgatca 29760
gcggtgtccg gggctgctag tcagcggcat tgtcggtgtg ctttcgggat tagcagtcat 29820
aatcatctgc atgttcattt ttgcttgctg ctatagaagg ctttaccgac aaaaatcaga 29880
cccactgctg aacctctatg tttaattttt tccagagcca tgaaggcagt tagcactcta 29940
gttttttgtt ctttgattgg cattgttttt agtgctgggt ttttgaaaaa tcttaccatt 30000
tatgaaggtg agaatgccac tctagtgggc atcagtggtc aaaatgtcag ctggctaaaa 30060
taccatctag atgggtggaa agacatttgc gattggaatg tcactgtgta tacatgtaat 30120
ggagttaacc tcaccattac taatgccacc caagatcaga atggtaggtt taagggtcag 30180
agtttcacta gaaataatgg gtatgaatcc cataacatgt ttatctatga cgtcactgtc 30240
atcagaaatg agaccgccac caccacacag atgcccacta cacacagttc taccactact 30300
accaagcaaa ccacacagac aaccactttt tatacatcaa ctcagcatat gaccaccact 30360
acagcagcaa agccaagtag cgcagcgcct cagccacagg ctttggcttt gaaagctgca 30420
caacctagta caactactaa gaccaatgag cagactactg attttttgtc cactgtcgag 30480
agccacacca cagctacctc cagtgccttc tctagcaccg ccaatctctc ctcgctttcc 30540
tctacaccaa tcagtcccgc tactactcct agccccgctc ctcttcccac tcccctgaag 30600
caaacagacg gcggcatgca atggcagatc accctgctca ttgtgatcgg gttggtcatc 30660
ctggccgtgt tgctctacta catcttctgc cgccgcattc ccaacgcgca ccgcaagccg 30720
gtctacaagc ccatcgttgt cgggcagccg gagccgcttc aggtggaagg gggtctaagg 30780
aatcttctct tctcttttac agtatggtga ttgaactatg attcctagac aattcttgat 30840
cactattctt atctgcctcc tccaagtctg tgccaccctc gctctggtgg ccaacgccag 30900
tccagactgt attgggccct tcgcctccta cgtgctcttt gccttcatca cctgcatctg 30960
ctgttgtagc atagtctgcc tgcttatcac cttcttccag ttcattgact ggatctttgt 31020
gcgcatcgcc tacctgcgcc accaccccca gtaccgcgac cagcgagtgg cgcgactgct 31080
caggctcctc tgataagcat gcgggctctg ctacttctcg cgcttctgct gttagtgctc 31140
ccccgtcccg tcgacccccg gtcccccgag gaggtccgca aatgcaaatt ccaagaaccc 31200
tggaaattcc tcaaatgcta ccgccaaaaa tcagacatgc atcccagctg gatcatgatc 31260
attgggatcg tgaacattct ggcctgcacc ctcatctcct ttgtgattta cccctgcttt 31320
gactttggtt ggaactcgcc agaggcactc tatctcccgc ctgagcctga cacaccacca 31380
cagcagcaac ctcaggcaca cgcactacca ccaccacagc ctaggccaca atacatgccc 31440
atattagact atgaggccga gccacagcga cccatgctcc ccgctattag ttacttcaat 31500
ctaaccggcg gagatgactg acccactggc caacaacaac gtcaacgacc ttctcctgga 31560
catggacggc cgcgcctcgg agcagcgact cgcccaactc cgcatccgcc agcagcagga 31620
gagagccgtc aaggagctgc aggatgcggt ggccatccac cagtgcaaga aaggcatctt 31680
ctgcctggtg aagcaggcca agatctccta cgaggtcacc cagaccgacc atcgcctctc 31740
ctacgagctc ctgcagcagc gccagaagtt cacctgcctg gtcggagtca accccatcgt 31800
catcacccag cagtcgggcg ataccaaggg gtgcatccac tgctcctgcg actcccccga 31860
gtgcgttcac accatgatca agaccctctg cggcctccgc gacctcctcc ccatgaacta 31920
atcaccccct tatccagtga aataaagatc atattgatga tgatttaaat aaaaaaataa 31980
tcatttgatt tgaaataaag atacaatcat attgatgatt tgagtttaac aaaaataaag 32040
aatcacttac ttgaaatctg ataccaggtc tctgtccatg ttttctgcca acaccacctc 32100
actcccctct tcccagctct ggtactgcag gccccggcgg gctgcaaact tcctccacac 32160
gctgaagggg atgtcaaatt cctcctgtcc ctcaatcttc attttctctt ctatcagatg 32220
tccaaaaagc gcgcgcgggt ggatgatgac ttcgaccccg tgtaccccta cgatgcagac 32280
aacgcaccga ctgtgccctt catcaaccct cccttcgtct cttcagatgg attccaagaa 32340
aagcccctgg gggtgttgtc cctgcgactg gccgatcccg tcaccaccaa gaacggggct 32400
gtcaccctca agctggggga gggggtggac ctcgacgact cgggaaaact catctccaaa 32460
aatgccacca aggccactgc ccctctcagt atttccaaca acaccatttc ccttaacatg 32520
gatacccctc tttacaacaa caatggaaag ctaggtatga aggtaaccgc accattaaag 32580
atattagaca cagatctact aaaaacactt gttgttgctt atgggcaggg attaggaaca 32640
aacaccaatg gtgctcttgt tgcccaacta gcatacccac ttgtttttaa taccgctagc 32700
aaaattgccc ttaatttagg caatggacca ttaaaagtgg atgcaaatag actgaacatt 32760
aattgcaaaa gaggtatcta tgtcactacc acaaaagatg cactggagat taatatcagt 32820
tgggcaaatg ctatgacatt tataggaaat gccattggtg tcaatattga cacaaaaaaa 32880
ggcctacagt tcggcacttc aagcactgaa acagatgtta aaaatgcttt tccactccaa 32940
gtaaaacttg gagctggtct tacatttgac agcacaggtg ccattgttgc ttggaacaaa 33000
gaagatgaca aacttacact gtggaccaca gccgatccat ctccaaactg tcacatatat 33060
tctgcaaagg atgctaagct tacactctgc ttgacaaagt gtggtagtca gatactgggc 33120
actgtttctc tcatagctgt tgatactggt agcttaaatc caataacagg aaaagtaacc 33180
actgctcttg tttcacttaa attcgatgcc aatggagttt tgcaagccag ttcaacacta 33240
gataaagaat attggaattt cagaaaagga gatgtgacac ctgctgaccc ctacactaat 33300
gctataggct ttatgcccaa ccttaatgca tacccaaaaa acacaaacgc agctgcaaaa 33360
agtcacattg ttggaaaagt atacctacat ggggatgaaa gcaagccact agacttgata 33420
attacattta atgaaaccag tgatgaatcc tgtacttatt gcattaactt tcagtggcag 33480
tggggaactg accaatataa agatgaaaca cttgcagtca gttcattcac cttctcatac 33540
attgctaaag aataacatcc accctgcatg ccaacccatt tccctctatc tatacatgga 33600
aaactctgaa gcagaaaaaa taaagttcaa gtgttttatt gattcaacag tttttacaga 33660
attcgagtag ttattttccc tccaccctcc caactcatgg aatacaccat cctctcccca 33720
cgcacagcct taaacatctg aatgccattg gtaatggaca tggttttggc ctccacattc 33780
cacacagttt cagagcgagc cagtctcggg tcggtcaggg agatgaaacc ctccgggcac 33840
tcctgcatct gcacctcaca gttcaacagc tgagggctgt cctcggtggt cgggatcaca 33900
gttatctgga agaagagcga tgagagtcat aatccgcgaa cgggatcggg cggttgtggc 33960
gcatcaggcc ccgcagcagt cgctgtctgc gccgctccgt caagctgctg ctcaaggggt 34020
ccgggtccag ggactccccg cgcatgatgc cgatggccct gagcatcagt cgcctggtgc 34080
ggcgggcgca gcagcggatg cggatctcac tcaggtcgga acagtacgtg cagcacagca 34140
ctaccaagtt gttcaacagt ccatagttca acgtgctcca gccaaaactc atctgtggaa 34200
ctatgctgcc cacatgtcca tcgtaccaga tcctgatgta aatcaggtgg cgccccctcc 34260
agaacacact gcccatgtac atgatctcct tgggcatgtg caggttcacc acctcccggt 34320
accacatcac ccgctggttg aacatgcagc cccggatgat cctgcggaac cacagggcca 34380
gcaccgcccc gcccgccatg cagcgcaggg accccgggtc ctggcaatgg cagtggatga 34440
tccaccgctc gtacccgtgg atcatctggg agctgaacaa gtctatgttg gcacagcaca 34500
ggcacacgct catgcatctc ttcagcactc tcagctcctc gggggtcaaa accatatccc 34560
agggtacggg gaactcttgc aggacagcga accccgcaga acagggcaaa cctcgcacag 34620
aacttacatt gtgcatggac agggtatcgc aatcaggcag caccgggtga tcctccacca 34680
gggaagcgcg ggtctcgatt tcctcacagc gtggtaaggg ggccggtcga tacgggtgat 34740
ggcgggacgc ggctgatcgt gttcgcgatc gtgtcatgat gcagttgctt tcggacattt 34800
tcgtacttgc tatagcagaa cctggtccgg gcgctgcaca ccgatcgccg gcggcggtct 34860
cggcgcttgg aacgctccgt gttgaaattg taaaacagcc actctctcag accgtgcagc 34920
agatctaggg cctcaggagt gatgaagatc ccatcatgcc tgatggctct gatcacatcg 34980
accaccgtgg aatgggccag acccagccag atgatgcaat tttgttgggt ttcggtgacg 35040
gcgggggagg gaagaacagg aagaaccatg attaacttta atccaaacgg tctcggagca 35100
cttcaaaatg aaggtcgcgg agatggcacc tctcgccccc gctgtgttgg tggaaaataa 35160
cagccaggtc aaaggtgata cggttctcga gatgttccac ggtggcttcc agcaaagcct 35220
ccacgcgcac atccagaaac aagacaatag cgaaagcggg agggttctct aattcctcaa 35280
tcatcatgtt acactcctgc accatcccca gataattttc atttttccag ccttgaatga 35340
ttcgaactag ttcctgaggt aaatccaagc cagccatgat aaagagctcg cgcagagcgc 35400
cctccaccgg cattcttaag cacaccctca taattccaag atattctgct cctggttcac 35460
ctgcagcaga ttgacaagcg gaatatcaaa ctctctgccg cgatccctaa gctcctccct 35520
cagcaataac tgtaagtact ctctcatatc ctctccgaaa tttttagcca taggaccgcc 35580
aggaataaga ttagggcaag ccacagtaca gataaaccga agtcctcccc agtgagcatt 35640
gccaaatgca agactgctat aagcatgctg gctagacccg gtgatatctt ccagataatt 35700
ggacagaaaa tcgcccaggc aatttttaag aaaatcaaca aaagaaaaat cctccaggtg 35760
cacgtttaga gcctcgggaa caacgatgga gtaaatgcaa gcggtgcgtt ccagcatggt 35820
tagttagctg atctgtagaa aaaacaaaaa tgaacattaa accatgctag cctggcgaac 35880
aggtgggtaa atcgttcttt ccagcaccag gcaggccacg gggtctccgg cgcgaccctc 35940
gtaaaaattg tcgctatgat tgaaaaccat cacagagaga cgttcccggt ggccggcgtg 36000
aatgattcga caagacgaat acacccccgg aacattggcg tccgcgagtg aaaaaaagcg 36060
cccgaggaag caataaggca ctacaatgct cagtctcaag tccagcaaag cgatgccatg 36120
cggatgaagc acaaaattct caggtgcgta caaaatgtaa ttactcccct cctgcacagg 36180
cagcaaagcc cccgatccct ccaggtacac atacaaagcc tcagcgtcca tagcttaccg 36240
agcagcagcg gcacacaaca ggcgcaaaag tcagagaaag gctgagagct ctaacctgtc 36300
cacccgctct ctgctcaata tatagcccag atctacactg acgtaaaggc caaagtctaa 36360
aaatacccgc caaataatca cacacgccca gcacacgccc agaaaccggt gacacactca 36420
gaaaaatacg cgcacttcct caaacgccca aactgccgtc atttccgggt tcccacgcta 36480
cgtcatcaaa attcaacttt caaattccgt cgaccgttaa aaacgtcacc cgccccgccc 36540
ctaacggtcg ccgctcccgc agccaatcag cgccccgcat ccccaaattc aaacggctca 36600
tttgcatatt aacgcgcacc aaaagtttga ggtatattat tgatgatg 36648
<210> 3
<211> 36606
<212> DNA
<213> 黑猩猩Pan 6 (CV32)基因组
<400> 3
catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agctgtttga 60
atttggggag ggaggaaggt gattggctgc gggagcggcg accgttaggg gcggggcggg 120
tgacgttttg atgacgtggc tatgaggcgg agccggtttg caagttctcg tgggaaaagt 180
gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240
ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300
aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360
ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420
ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480
tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540
cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600
gtaatgtttt cctggctact gggaacgaga ttctggaatt ggtggtggac gccatgatgg 660
gtgacgaccc tccagagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720
atctggaggt ggatgtgccc gagagcgacc ctaacgagga ggcggtgaat gatttgttta 780
gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840
cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900
aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960
aggaggcgat tcgagctgcg gtgaaccagg gagtgaaaac tgcgggcgag agctttagcc 1020
tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080
ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140
acagtaagtg tgattaactt tagttgggaa ggcagagggt gactgggtgc tgactggttt 1200
atttatgtat atgttttttt atgtgtaggt cccgtctctg acgtagatga gacccccact 1260
tcagagtgca tttcatcacc cccagaaatt ggcgaggaac cgcccgaaga tattattcat 1320
agaccagttg cagtgagagt caccgggcgg agagcagctg tggagagttt ggatgacttg 1380
ctacagggtg gggatgaacc tttggacttg tgtacccgga aacgccccag gcactaagtg 1440
ccacacatgt gtgtttactt aaggtgatgt cagtatttat agggtgtgga gtgcaataaa 1500
atccgtgttg actttaagtg cgtgttttat gactcagggg tggggactgt gggtatataa 1560
gcaggtgcag acctgtgtgg tcagttcaga gcaggactca tggagatctg gactgtcttg 1620
gaagactttc accagactag acagttgcta gagaactcat cggagggagt ctcttacctg 1680
tggagattct gcttcggtgg gcctctagct aagctagtct atagggccaa acaggattat 1740
aaggaacaat ttgaggatat tttgagagag tgtcctggta tttttgactc tctcaacttg 1800
ggccatcagt ctcactttaa ccagagtatt ctgagagccc ttgacttttc tactcctggc 1860
agaactaccg ccgcggtagc cttttttgcc tttattcttg acaaatggag tcaagaaacc 1920
catttcagca gggattaccg tctggactgc ttagcagtag ctttgtggag aacatggagg 1980
tgccagcgcc tgaatgcaat ctccggctac ttgccagtac agccggtaga cacgctgagg 2040
atcctgagtc tccagtcacc ccaggaacac caacgccgcc agcagccgca gcaggagcag 2100
cagcaagagg aggaccgaga agagaacccg agagccggtc tggaccctcc ggtggcggag 2160
gaggaggagt agctgacttg tttcccgagc tgcgccgggt gctgactagg tcttccagtg 2220
gacgggagag ggggattaag cgggagaggc atgaggagac tagccacaga actgaactga 2280
ctgtcagtct gatgagccgc aggcgcccag aatcggtgtg gtggcatgag gtgcagtcgc 2340
aggggataga tgaggtctcg gtgatgcatg agaaatattc cctagaacaa gtcaagactt 2400
gttggttgga gcccgaggat gattgggagg tagccatcag gaattatgcc aagctggctc 2460
tgaagccaga caagaagtac aagattacca aactgattaa tatcagaaat tcctgctaca 2520
tttcagggaa tggggccgag gtggagatca gtacccagga gagggtggcc ttcagatgtt 2580
gtatgatgaa tatgtacccg ggggtggtgg gcatggaggg agtcaccttt atgaacacga 2640
ggttcagggg tgatgggtat aatggggtgg tctttatggc caacaccaag ctgacagtgc 2700
acggatgctc cttctttggc ttcaataaca tgtgcatcga ggcctggggc agtgtttcag 2760
tgaggggatg cagcttttca gccaactgga tgggggtcgt gggcagaacc aagagcaagg 2820
tgtcagtgaa gaaatgcctg ttcgagaggt gccacctggg ggtgatgagc gagggcgaag 2880
ccaaagtcaa acactgcgcc tctaccgaga cgggctgctt tgtgctgatc aagggcaatg 2940
cccaagtcaa gcataacatg atctgtgggg cctcggatga gcgcggctac cagatgctga 3000
cctgcgccgg tgggaacagc catatgctgg ccaccgtgca tgtggcctcg cacccccgca 3060
agacatggcc cgagttcgag cacaacgtca tgacccgctg caatgtgcac ctgggctccc 3120
gccgaggcat gttcatgccc taccagtgca acatgcaatt tgtgaaggtg ctgctggagc 3180
ccgatgccat gtccagagtg agcctgacgg gggtgtttga catgaatgtg gagctgtgga 3240
aaattctgag atatgatgaa tccaagacca ggtgccgggc ctgcgaatgc ggaggcaagc 3300
acgccaggct tcagcccgtg tgtgtggagg tgacggagga cctgcgaccc gatcatttgg 3360
tgttgtcctg caacgggacg gagttcggct ccagcgggga agaatctgac tagagtgagt 3420
agtgtttggg gctgggtgtg agcctgcatg aggggcagaa tgactaaaat ctgtggtttt 3480
ctgtgtgttg cagcagcatg agcggaagcg cctcctttga gggaggggta ttcagccctt 3540
atctgacggg gcgtctcccc tcctgggcgg gagtgtgtca gaatgttatg gnatccacgg 3600
tggacggccg gcccgtgcag cccgcgaact cttcaaccct gacctacgcg accctgagct 3660
cctcgtccgt ggacgcagct gccgccgcag ctgctgcttc cgccgccagc gccgtgcgcg 3720
gaatggccct gggcgccggc tactacagct ctctggtggc caactcgagt tccaccaata 3780
atcccgccag cctgaacgag gagaagctgc tgctgctgat ggcccagctc gaggccctga 3840
cccagcgcct gggcgagctg acccagcagg tggctcagct gcaggcggag acgcgggccg 3900
cggttgccac ggtgaaaacc aaataaaaaa tgaatcaata aataaacgga gacggttgtt 3960
gattttaaca cagagtcttg aatctttatt tgatttttcg cgcgcggtag gccctggacc 4020
accggtctcg atcattgagc acccggtgga tcttttccag gacccggtag aggtgggctt 4080
ggatgttgag gtacatgggc atgagcccgt cccgggggtg gaggtagctc cattgcaggg 4140
cctcgtgctc ggggatggtg ttgtaaatca cccagtcata gcaggggcgc agggcgtggt 4200
gctgcacgat gtccttgagg aggagactga tggccacggg cagccccttg gtgtaggtgt 4260
tgacgaacct gttgagctgg gagggatgca tgcgggggga gatgagatgc atcttggcct 4320
ggatcttgag attggcgatg ttcccgccca gatcccgccg ggggttcatg ttgtgcagga 4380
ccaccagcac ggtgtatccg gtgcacttgg ggaatttgtc atgcaacttg gaagggaagg 4440
cgtgaaagaa tttggagacg cccttgtgac cgcccaggtt ttccatgcac tcatccatga 4500
tgatggcgat gggcccgtgg gcggcggcct gggcaaagac gtttcggggg tcggacacat 4560
cgtagttgtg gtcctgggtg agctcgtcat aggccatttt aatgaatttg gggcggaggg 4620
tgcccgactg ggggacgaag gtgccctcga tcccgggggc gtagttgccc tcgcagatct 4680
gcatctccca ggccttgagc tcggaggggg ggatcatgtc cacctgcggg gcgatgaaaa 4740
aaacggtttc cggggcgggg gagatgagct gggccgaaag caggttccgg agcagctggg 4800
acttgccgca accggtgggg ccgtagatga ccccgatgac cggctgcagg tggtagttga 4860
gggagagaca gctgccgtcc tcgcggagga ggggggccac ctcgttcatc atctcgcgca 4920
catgcatgtt ctcgcgcacg agttccgcca ggaggcgctc gccccccagc gagaggagct 4980
cttgcagcga ggcgaagttt ttcagcggct tgagtccgtc ggccatgggc attttggaga 5040
gggtctgttg caagagttcc agacggtccc agagctcggt gatgtgctct agggcatctc 5100
gatccagcag acctcctcgt ttcgcgggtt ggggcgactg cgggagtagg gcaccaggcg 5160
atgggcgtcc agcgaggcca gggtccggtc cttccagggc cgcagggtcc gcgtcagcgt 5220
ggtctccgtc acggtgaagg ggtgcgcgcc gggctgggcg cttgcgaggg tgcgcttcag 5280
gctcatccgg ctggtcgaga accgctcccg gtcggcgccc tgcgcgtcgg ccaggtagca 5340
attgagcatg agttcgtagt tgagcgcctc ggccgcgtgg cccttggcgc ggagcttacc 5400
tttggaagtg tgtccgcaga cgggacagag gagggacttg agggcgtaga gcttgggggc 5460
gaggaagacg gactcggggg cgtaggcgtc cgcgccgcag ctggcgcaga cggtctcgca 5520
ctccacgagc caggtgaggt cggggcggtt ggggtcaaaa acgaggtttc ctccgtgctt 5580
tttgatgcgt ttcttacctc tggtctccat gagctcgtgt ccccgctggg tgacaaagag 5640
gctgtccgtg tccccgtaga ccgactttat gggccggtcc tcgagcgggg tgccgcggtc 5700
ctcgtcgtag aggaaccccg cccactccga gacgaaggcc cgggtccagg ccagcacgaa 5760
ggaggccacg tgggaggggt agcggtcgtt gtccaccagc gggtccacct tctccagggt 5820
atgcaagcac atgtccccct cgtccacatc caggaaggtg attggcttgt aagtgtaggc 5880
cacgtgaccg ggggtcccgg ccgggggggt ataaaagggg gcgggcccct gctcgtcctc 5940
actgtcttcc ggatcgctgt ccaggagcgc cagctgttgg ggtaggtatt ccctctcgaa 6000
ggcgggcatg acctcggcac tcaggttgtc agtttctaga aacgaggagg atttgatatt 6060
gacggtgccg ttggagacgc ctttcatgag cccctcgtcc atttggtcag aaaagacgat 6120
ctttttgttg tcgagcttgg tggcgaagga gccgtagagg gcgttggaga gcagcttggc 6180
gatggagcgc atggtctggt tcttttcctt gtcggcgcgc tccttggcgg cgatgttgag 6240
ctgcacgtac tcgcgcgcca cgcacttcca ttcggggaag acggtggtga gctcgtcggg 6300
cacgattctg acccgccagc cgcggttgtg cagggtgatg aggtccacgc tggtggccac 6360
ctcgccgcgc aggggctcgt tggtccagca gaggcgcccg cccttgcgcg agcagaaggg 6420
gggcagcggg tccagcatga gctcgtcggg ggggtcggcg tccacggtga agatgccggg 6480
caggagctcg gggtcgaagt agctgatgca ggtgcccaga ttgtccagcg ccgcttgcca 6540
gtcgcgcacg gccagcgcgc gctcgtaggg gctgaggggc gtgccccagg gcatggggtg 6600
cgtgagcgcg gaggcgtaca tgccgcagat gtcgtagacg tagaggggct cctcgaggac 6660
gccgatgtag gtggggtagc agcgcccccc gcggatgctg gcgcgcacgt agtcgtacag 6720
ctcgtgcgag ggcgcgagga gccccgtgcc gaggttggag cgttgcggct tttcggcgcg 6780
gtagacgatc tggcggaaga tggcgtggga gttggaggag atggtgggcc tttggaagat 6840
gttgaagtgg gcgtggggca ggccgaccga gtccctgatg aagtgggcgt aggagtcctg 6900
cagcttggcg acgagctcgg cggtgacgag gacgtccagg gcgcagtagt cgagggtctc 6960
ttggatgatg tcatacttga gctggccctt ctgcttccac agctcgcggt tgagaaggaa 7020
ctcttcgcgg tccttccagt actcttcgag ggggaacccg tcctgatcgg cacggtaaga 7080
gcccaccatg tagaactggt tgacggcctt gtaggcgcag cagcccttct ccacggggag 7140
ggcgtaagct tgcgcggcct tgcgcaggga ggtgtgggtg agggcgaagg tgtcgcgcac 7200
catgaccttg aggaactggt gcttgaagtc gaggtcgtcg cagccgccct gctcccagag 7260
ttggaagtcc gtgcgcttct tgtaggcggg gttaggcaaa gcgaaagtaa catcgttgaa 7320
gaggatcttg cccgcgcggg gcatgaagtt gcgagtgatg cggaaaggct ggggcacctc 7380
ggcccggttg ttgatgacct gggcggcgag gacgatctcg tcgaagccgt tgatgttgtg 7440
cccgacgatg tagagttcca cgaatcgcgg gcggcccttg acgtggggca gcttcttgag 7500
ctcgtcgtag gtgagctcgg cggggtcgct gagcccgtgc tgctcgaggg cccagtcggc 7560
gacgtggggg ttggcgctga ggaaggaagt ccagagatcc acggccaggg cggtctgcaa 7620
gcggtcccgg tactgacgga actgttggcc cacggccatt ttttcggggg tgacgcagta 7680
gaaggtgcgg gggtcgccgt gccancggtc ccacttgagc tggagggcga ggtcgtgggc 7740
gagctcgacg agcggcgggt ccccggagag tttcatgacc agcatgaagg ggacgagctg 7800
cttgccgaag gaccccatcc aggtgtaggt ttccacatcg taggtgagga agagcctttc 7860
ggtgcgagga tgcgagccga tggggaagaa ctggatctcc tgccaccagt tggaggaatg 7920
gctgttgatg tgatggaagt agaaatgccg acggcgcgcc gagcactcgt gcttgtgttt 7980
atacaagcgt ccgcagtgct cgcaacgctg cacgggatgc acgtgctgca cgagctgtac 8040
ctgggttcct ttggcgagga atttcagtgg gcagtggagc gctggcggct gcatctcgtg 8100
ctgtactacg tcttggccat cggcgtggcc atcgtctgcc tcgatggtgg tcatgctgac 8160
gagcccgcgc gggaggcagg tccagacctc ggctcggacg ggtcggagag cgaggacgag 8220
ggcgcgcagg ccggagctgt ccagggtcct gagacgctgc ggagtcaggt cagtgggcag 8280
cggcggcgcg cggttgactt gcaggagctt ttccagggcg cgcgggaggt ccagatggta 8340
cttgatctcc acggcgccgt tggtggctac gtccacggct tgcagggtgc cgtgcccctg 8400
gggcgccacc accgtgcccc gtttcttctt gggcgctgct tccatgtcgg tcagaagcgg 8460
cggcgaggac gcgcgccggg cggcaggggc ggctcggggc ccggaggcag gggcggcagg 8520
ggcacgtcgg cgccgcgcgc gggcaggttc tggtactgcg cccggagaag actggcgtga 8580
gcgacgacgc gacggttgac gtcctggatc tgacgcctct gggtgaaggc cacgggaccc 8640
gtgagtttga acctgaaaga gagttcgaca gaatcaatct cggtatcgtt gacggcggcc 8700
tgccgcagga tctcttgcac gtcgcccgag ttgtcctggt aggcgatctc ggtcatgaac 8760
tgctcgatct cctcctcctg aaggtctccg cggccggcgc gctcgacggt ggccgcgagg 8820
tcgttggaga tgcggcccat gagctgcgag aaggcgttca tgccggcctc gttccagacg 8880
cggctgtaga ccacggctcc gtcggggtcg cgcgcgcgca tgaccacctg ggcgaggttg 8940
agctcgacgt ggcgcgtgaa gaccgcgtag ttgcagaggc gctggtagag gtagttgagc 9000
gtggtggcga tgtgctcggt gacgaagaag tacatgatcc agcggcggag cggcatctcg 9060
ctgacgtcgc ccagggcttc caagcgttcc atggcctcgt agaagtccac ggcgaagttg 9120
aaaaactggg agttgcgcgc cgagacggtc aactcctcct ccagaagacg gatgagctcg 9180
gcgatggtgg cgcgcacctc gcgctcgaag gccccggggg gctcctcttc catctcctcc 9240
tcttcctcct ccactaacat ctcttctact tcctcctcag gaggcggtgg cgggggaggg 9300
gccctgcgtc gccggcggcg cacgggcaga cggtcgatga agcgctcgat ggtctccccg 9360
cgccggcgac gcatggtctc ggtgacggcg cgcccgtcct cgcggggccg cagcatgaag 9420
acgccgccgc gcatctccag gtggccgccg ggggggtctc cgttgggcag ggagagggcg 9480
ctgacgatgc atcttatcaa ttgacccgta gggactccgc gcaaggacct gagcgtctcg 9540
agatccacgg gatccgaaaa ccgctgaacg aaggcttcga gccagtcgca gtcgcaaggt 9600
aggctgagcc cggtttcttg ttcttcgggt atttggtcgg gaggcggcgg gcgatgctgc 9660
tggtgatgaa gttgaagtag gcggtcctga gacggcggat ggtggcgagg agcaccaggt 9720
ccttgggccc ggcttgctgg atgcgcagac ggtcggccat gccccaggcg tggtcctgac 9780
acctggcgag gtccttgtag tagtcctgca tgagccgctc cacgggcacc tcctcctcgc 9840
ccgcgcggcc gtgcatgcgc gtgagcccga acccgcgctg cggctggacg agcgccaggt 9900
cggcgacgac gcgctcggtg aggatggcct gctggatctg ggtgagggtg gtctggaagt 9960
cgtcgaagtc gacgaagcgg tggtaggctc cggtgttgat ggtgtaggag cagttggcca 10020
tgacggacca gttgacggtc tggtggccgg gtcgcacgag ctcgtggtac ttgaggcgcg 10080
agtaggcgcg cgtgtcgaag atgtagtcgt tgcaggcgcg cacgaggtac tggtatccga 10140
cgaggaagtg cggcggcggc tggcggtaga gcggccatcg ctcggtggcg ggggcgccgg 10200
gcgcgaggtc ctcgagcatg aggcggtggt agccgtagat gtacctggac atccaggtga 10260
tgccggcggc ggtggtggag gcgcgcggga actcgcggac gcggttccag atgttgcgca 10320
gcggcaggaa gtagttcatg gtggccgcgg tctggcccgt gaggcgcgcg cagtcgtgga 10380
tgctctagac atacgggcaa aaacgaaagc ggtcagcggc tcgactccgt ggcctggagg 10440
ctaagcgaac gggttgggct gcgcgtgtac cccggttcga atctcgaatc aggctggagc 10500
cgcagctaac gtggtactgg cactcccgtc tcgacccaag cctgctaacg aaacctccag 10560
gatacggagg cgggtcgttt tttggccttg gtcgctggtc atgaaaaact agtaagcgcg 10620
gaaagcggcc gcccgcgatg gctcgctgcc gtagtctgga gaaagaatcg ccagggttgc 10680
gttgcggtgt gccccggttc gagcctcagc gctcggcgcc ggccggattc cgcggctaac 10740
gtgggcgtgg ctgccccgtc gtttccaaga ccccttagcc agccgacttc tccagttacg 10800
gagcgagccc ctcttttttt ttcttgtgtt tttgccagat gcatcccgta ctgcggcaga 10860
tgcgccccca ccctccacca caaccgcccc taccgcagca gcagcaacag ccggcgcttc 10920
tgcccccgcc ccagcagcag ccagccacta ccgcggcggc cgccgtgagc ggagccggcg 10980
ttcagtatga cctggccttg gaagagggcg aggggctggc gcggctgggg gcgtcgtcgc 11040
cggagcggca cccgcgcgtg cagatgaaaa gggacgctcg cgaggcctac gtgcccaagc 11100
agaacctgtt cagagacagg agcggcgagg agcccgagga gatgcgcgcc tcccgcttcc 11160
acgcggggcg ggagctgcgg cgcggcctga accgaaagcg ggtgctgagg gacgaggatt 11220
tcgaggcgga cgagctgacg gggatcagcc ccgtgcgcgc gcacgtggtc gnggncaacc 11280
tggtcacggc gtacgagcag accgtgaagg aggagagcaa cttccaaaaa tccttcaaca 11340
accacgtgcg caccttgatc gcgcgcgagg aggtgaccct gggcctgatg cacctgtggg 11400
acctgctgga ggccatcgtg cagaacccca cgagcaagcc gctgacggcg cagctgtttc 11460
tggtggtgca gcacagtcgg gacaacgaga cgttcaggga ggcgctgctg aatatcaccg 11520
agcccgaggg ccgctggctc ctggacctgg tgaacatttt gcagagcatc gtggtgcagg 11580
agcgcgggct gccgctgtcc gagaagctgg cggccatcaa cttctcggtg ctgagtctgg 11640
gcaagtacta cgctaggaag atctacaaga ccccgtacgt gcccatagac aaggaggtga 11700
agatcgacgg gttttacatg cgcatgaccc tgaaagtgct gaccctgagc gacgatctgg 11760
gggtgtaccg caacgacagg atgcaccgcg cggtgagcgc cagccgccgg cgcgagctga 11820
gcgaccagga gctgatgcac agcctgcagc gggccctgac cggggccggg accgaggggg 11880
agagctactt tgacatgggc gcggacctgc gctggcagcc cagccgccgg gccttggaag 11940
ctgccggcgg ttccccctac gtggaggagg tggacgatga ggaggaggag ggcgagtacc 12000
tggaagactg atggcgcgac cgtatttttg ctagatgcag caacagccac cgccgccgcc 12060
tcctgatccc gcgatgcggg cggcgctgca gagccagccg tccggcatta actcctcgga 12120
cgattggacc caggccatgc aacgcatcat ggcgctgacg acccgcaatc ccgaagcctt 12180
tagacagcag cctcaggcca accggctctc ggccatcctg gaggccgtgg tgccctcgcg 12240
ctcgaacccc acgcacgaga aggtgctggc catcgtgaac gcgctggtgg agaacaaggc 12300
catccgcggt gacgaggccg ggctggtgta caacgcgctg ctggagcgcg tggcccgcta 12360
caacagcacc aacgtgcaga cgaacctgga ccgcatggtg accgacgtgc gcgaggcggt 12420
gtcgcagcgc gagcggttcc accgcgagtc gaacctgggc tccatggtgg cgctgaacgc 12480
cttcctgagc acgcagcccg ccaacgtgcc ccggggccag gaggactaca ccaacttcat 12540
cagcgcgctg cggctgatgg tggccgaggt gccccagagc gaggtgtacc agtcggggcc 12600
ggactacttc ttccagacca gtcgccaggg cttgcagacc gtgaacctga gccaggcttt 12660
caagaacttg cagggactgt ggggcgtgca ggccccggtc ggggaccgcg cgacggtgtc 12720
gagcctgctg acgccgaact cgcgcctgct gctgctgctg gtggcgccct tcacggacag 12780
cggcagcgtg agccgcgact cgtacctggg ctacctgctt aacctgtacc gcgaggccat 12840
cggacaggcg cacgtggacg agcagaccta ccaggagatc acccacgtga gccgcgcgct 12900
gggccaggag gacccgggca acctggaggc caccctgaac ttcctgctga ccaaccggtc 12960
gcagaagatc ccgccccagt acgcgctgag caccgaggag gagcgcatcc tgcgctacgt 13020
gcagcagagc gtggggctgt tcctgatgca ggagggggcc acgcccagcg cggcgctcga 13080
catgaccgcg cgcaacatgg agcccagcat gtacgcccgc aaccgcccgt tcatcaataa 13140
gctgatggac tacttgcatc gggcggccgc catgaactcg gactacttta ccaacgccat 13200
cttgaacccg cactggctcc cgccgcccgg gttctacacg ggcgagtacg acatgcccga 13260
ccccaacgac gggttcctgt gggacgacgt ggacagcagc gtgttctcgc cgcgtccagg 13320
aaccaatgcc gtgtggaaga aagagggcgg ggaccggcgg ccgtcctcgg cgctgtccgg 13380
tcgcgcgggt gctgccgcgg cggtgcccga ggccgccagc cccttcccga gcctgccctt 13440
ttcgctgaac agcgtgcgca gcagcgagct gggtcggctg acgcgaccgc gcctgctggg 13500
cgaggaggag tacctgaacg actccttgtt gaggcccgag cgcgagaaga acttccccaa 13560
taacgggata gagagcctgg tggacaagat gagccgctgg aagacgtacg cgcacgagca 13620
cagggacgag ccccgagcta gcagcgcagg cacccgtaga cgccagcggc acgacaggca 13680
gcggggactg gtgtgggacg atgaggattc cgccgacgac agcagcgtgt tggacttggg 13740
tgggagtggt ggtaacccgt tcgctcacct gcgcccccgt atcgggcgcc tgatgtaaga 13800
atctgaaaaa ataaaagacg gtactcacca aggccatggc gaccagcgtg cgttcttctc 13860
tgttgtttgt agtagtatga tgaggcgcgt gtacccggag ggtcctcctc cctcgtacga 13920
gagcgtgatg cagcaggcgg tggcggcggc gatgcagccc ccgctggagg cgccttacgt 13980
gcccccgcgg tacctggcgc ctacggaggg gcggaacagc attcgttact cggagctggc 14040
acccttgtac gataccaccc ggttgtacct ggtggacaac aagtcggcag acatcgcctc 14100
gctgaactac cagaacgacc acagcaactt cctgaccacc gtggtgcaga acaacgattt 14160
cacccccacg gaggccagca cccagaccat caactttgac gagcgctcgc ggtggggcgg 14220
ccagctgaaa accatcatgc acaccaacat gcccaacgtg aacgagttca tgtacagcaa 14280
caagttcaag gcgcgggtga tggtctcgcg caagaccccc aacggggtgg atgatgatta 14340
tgatggtagt caggacgagc tgacctacga gtgggtggag tttgagctgc ccgagggcaa 14400
cttctcggtg accatgacca tcgatctgat gaacaacgcc atcatcgaca actacttggc 14460
ggtggggcgg cagaacgggg tgctggagag cgacatcggc gtgaagttcg acacgcgcaa 14520
cttccggctg ggctgggacc ccgtgaccga gctggtgatg ccgggcgtgt acaccaacga 14580
ggccttccac cccgacatcg tcctgctgcc cggctgcggc gtggacttca ccgagagccg 14640
cctcagcaac ctgctgggca tccgcaagcg gcagcccttc caggagggct tccagatcct 14700
gtacgaggac ctggaggggg gcaacatccc cgcgctcttg gatgtcgaag cctacgagaa 14760
aagcaaggag gatagcaccg ccgcggcgac cgcagccgtg gccaccgcct ctaccgaggt 14820
gcggggcgat aattttgcta gcgctgcggc agcggccgag gcggctgaaa ccgaaagtaa 14880
gatagtcatc cagccggtgg agaaggacag caaggacagg agctacaacg tgctcgcgga 14940
caagaaaaac accgcctacc gcagctggta cctggcctac aactacggcg accccgagaa 15000
gggcgtgcgc tcctggacgc tgctcaccac ctcggacgtc acctgcggcg tggagcaagt 15060
ctactggtcg ctgcccgaca tgatgcaaga cccggtcacc ttccgctcca cgcgtcaagt 15120
tagcaactac ccggtggtgg gcgccgagct cctgcccgtc tactccaaga gcttcttcaa 15180
cgagcaggcc gtctactcgc agnagctgcg cgccttcacc tcgctcacgc acgtcttcaa 15240
ccgcttcccc gagaaccaga tcctcgtccg ccgccgcgcc caccattacc accgtcagtg 15300
aaaacgttcc tgctctcaca gatcacggga ccctgccgct gcgcagcagt atccggggag 15360
tccagcgcgt gaccgtcact gacgccagac gccgcacctg cccctacgtc tacaaggccc 15420
tgggcgtagt cgcgccgcgc gtcctctcga gccgcacctt ctaaaaaatg tccattctca 15480
tctcgcccag taataacacc ggttggggcc tgcgcgcgcc cagcaagatg tacggaggcg 15540
ctcgccaacg ctccacgcaa caccccgtgc gcgtgcgcgg gcacttccgc gctccctggg 15600
gcgccctcaa gggccgcgtg cgctcgcgca ccaccgtcga cgacgtgatc gaccaggtgg 15660
tggccgacgc gcgcaactac acgcccgccg ccgcgcccgt ctccaccgtg gacgccgtca 15720
tcgacagcgt ggtggccgac gcgcgccggt acgcccgcac caagagccgg cggcggcgca 15780
tcgcccggcg gcaccggagc acccccgcca tgcgcgcggc gcgagccttg ctgcgcaggg 15840
ccaggcgcac gggacgcagg gccatgctca gggcggccag acgcgcggcc tccggcagca 15900
gcagcgccgg caggacccgc agacgcgcgg ccacggcggc ggcggcggcc atcgccagca 15960
tgtcccgccc gcggcgcggc aacgtgtact gggtgcgcga cgccgccacc ggtgtgcgcg 16020
tgcccgtgcg cacccgcccc cctcgcactt gaagatgctg acttcgcgat gttgatgtgt 16080
cccagcggcg aggaggatgt ccaagcgcaa atacaaggaa gagatgctcc aggtcatcgc 16140
gcctgagatc tacggccccg cggcggcggt gaaggaggaa agaaagcccc gcaaactgaa 16200
gcgggtcaaa aaggacaaaa aggaggagga agatgacgga ctggtggagt ttgtgcgcga 16260
gttcgccccc cggcggcgcg tgcagtggcg cgggcggaaa gtgaaaccgg tgctgcggcc 16320
cggcaccacg gtggtcttca cgcccggcga gcgttccggc tccgcctcca agcgctccta 16380
cgacgaggtg tacggggacg aggacatcct cgagcaggcg gtcgagcgtc tgggcgagtt 16440
tgcgtacggc aagcgcagcc gccccgcgcc cttgaaagag gaggcggtgt ccatcccgct 16500
ggaccacggc aaccccacgc cgagcctgaa gccggtgacc ctgcagcagg tgctaccgag 16560
cgcggcgccg cgccggggct tcaagcgcga gggcggcgag gatctgtacc cgaccatgca 16620
gctgatggtg cccaagcgcc agaagctgga ggacgtgctg gagcacatga aggtggaccc 16680
cgaggtgcag cccgaggtca aggtgcggcc catcaagcag gtggccccgg gcctgggcgt 16740
gcagaccgtg gacatcaaga tccccacgga gcccatggaa acgcagaccg agcccgtgaa 16800
gcccagcacc agcaccatgg aggtgcagac ggatccctgg atgccagcac cagcttccac 16860
cagcactcgc cgaagacgca agtacggcgc ggccagcctg ctgatgccca actacgcggc 16920
tgcatccttc catcatcccc acgccgggct accgcggcac gcgcttctac cgcggctaca 16980
ccagcagccg ccgccgcaag accaccaccc gccgccgtcg tcgcagccgc cgcagcagca 17040
ccgcgacttc cgccttggtg cggagagtgt atcgcagcgg gcgcgagcct ctgaccctgc 17100
cgcgcgcgcg ctaccacccg agcatcgcca tttaactacc gcctcctact tgcagatatg 17160
gccctcacat gccgcctccg cgtccccatt acgggctacc gaggaagaaa gccgcgccgt 17220
agaaggctga cggggaacgg gctgcgtcgc catcaccacc ggcggcggcg cgccatcagc 17280
aagcggttgg ggggaggctt cctgcccgcg ctgatcccca tcatcgccgc ggcgatcggg 17340
gcgatccccg gcatagcttc cgtggcggtg caggcctctc agcgccactg agacacaaaa 17400
aagcatggat ttgtaataaa aaaaaaaatg gactgacgct cctggtcctg tgatgtgtgt 17460
ttttagatgg aagacatcaa tttttcgtcc ctggcaccgc gacacggcac gcggccgttt 17520
atgggcacct ggagcgacat cggcaacagc caactgaacg ggggcgcctt caattggagc 17580
agtctctgga gcgggcttaa gaatttcggg tccacgctca aaacctatgg caacaaggcg 17640
tggaacagca gcacagggca ggcgctgagg gaaaagctga aagaacagaa cttccagcag 17700
aaggtggttg atggcctggc ctcaggcatc aacggggtgg ttgacctggc caaccaggcc 17760
gtgcagaaac agatcaacag ccgcctggac gcggtcccgc ccgcggggtc cgtggagatg 17820
ccccaggtgg aggaggagct gcctcccctg gacaagcgcg gcgacaagcg accgcgtccc 17880
gacgcggagg agacgctgct gacgcacacg gacgagccgc ccccgtacga ggaggcggtg 17940
aaactgggcc tgcccaccac gcggcccgtg gcgcctctgg ccaccggagt gctgaaaccc 18000
agcagcagcc agcccgcgac cctggacttg cctccgcctc gcccctccac agtggctaag 18060
cccctgccgc cggtggccgt cgcgtcgcgc gccccccgag gccgccccca ggcgaactgg 18120
cagagcactc tgaacagcat cgtgggtctg ggagtgcaga gtgtgaagcg ccgccgctgc 18180
tattaaaaga cactgtagcg cttaacttgc ttgtctgtgt gtatatgtat gtccgccgac 18240
cagaaggagg agtgtgaaga ggcgcgtcgc cgagttgcaa gatggccacc ccatcgatgc 18300
tgccccagtg ggcgtacatg cacatcgccg gacaggacgc ttcggagtac ctgagtccgg 18360
gtctggtgca gttcgcccgc gccacagaca cctacttcag tctggggaac aagtttagga 18420
accccacggt ggcgcccacg cacaatgtga ccaccgaccg cagccagcgg ctgacggtgc 18480
gcttcgtgcc cgtggaccgc gaggacaaca cctactcgta caaagtgcgc tacacgctgg 18540
ccgtgggcga caaccgcgtg ctggacatgg ccagcaccta ctttgacatc cgcggcgtgc 18600
tggaccgggg ccctagcttc aaaccctact ctggcaccgc ctacaacagc ctagctccca 18660
agggagctcc caattccagc cagtgggagc aagcaaaaac aggcaatggg ggaactatgg 18720
aaacacacac atatggtgtg gccccaatgg gcggagagaa tattacaaaa gatggtcttc 18780
aaattggaac tgacgttaca gcgaatcaga ataaaccaat ttatgccgac aaaacatttc 18840
aaccagaacc gcaagtagga gaagaaaatt ggcaagaaac tgaaaacttt tatggcggta 18900
gagctcttaa aaaagacaca aacatgaaac cttgctatgg ctcctatgct agacccacca 18960
atgaaaaagg aggtcaagct aaacttaaag ttggagatga tggagttcca accaaagaat 19020
tcgacataga cctggctttc tttgatactc ccggtggcac cgtgaacggt caagacgagt 19080
ataaagcaga cattgtcatg tataccgaaa acacgtattt ggaaactcca gacacgcatg 19140
tggtatacaa accaggcaag gatgatgcaa gttctgaaat taacctggtt cagcagtcta 19200
tgcccaacag acccaactac attgggttca gggacaactt tatcggtctt atgtactaca 19260
acagcactgg caatatgggt gtgcttgctg gtcaggcctc ccagctgaat gctgtggttg 19320
atttgcaaga cagaaacacc gagctgtcct accagctctt gcttgactct ttgggtgaca 19380
gaacccggta tttcagtatg tggaaccagg cggtggacag ttatgacccc gatgtgcgca 19440
tcatcgaaaa ccatggtgtg gaggatgaat tgccaaacta ttgcttcccc ttggacggct 19500
ctggcactaa cgccgcatac caaggtgtga aagtaaaaga tggtcaagat ggtgatgttg 19560
agagtgaatg ggaaaatgac gatactgttg cagctcgaaa tcaattatgt aaaggtaaca 19620
ttttcgccat ggagattaat ctccaggcta acctgtggag aagtttcctc tactcgaacg 19680
tggccctgta cctgcccgac tcctacaagt acacgccgac caacgtcacg ctgccgacca 19740
acaccaacac ctacgattac atgaatggca gagtgacacc tccctcgctg gtagacgcct 19800
acctcaacat cggggcgcgc tggtcgctgg accccatgga caacgtcaac cccttcaacc 19860
accaccgcaa cgcgggcctg cgctaccgct ccatgctcct gggcaacggg cgctacgtgc 19920
ccttccacat ccaggtgccc caaaagtttt tcgccatcaa gagcctcctg ctcctgcccg 19980
ggtcctacac ctacgagtgg aacttccgca aggacgtcaa catgatcctg cagagctccc 20040
taggcaacga cctgcgcacg gacggggcct ccatcgcctt caccagcatc aacctctacg 20100
ccaccttctt ccccatggcg cacaacaccg cctccacgct cgaggccatg ctgcgcaacg 20160
acaccaacga ccagtccttc aacgactacc tctcggcggc caacatgctc taccccatcc 20220
cggccaacgc caccaacgtg cccatctcca tcccctcgcg caactgggcc gccttccgcg 20280
gatggtcctt cacgcgcctg aagacccgcg agacgccctc gctcggctcc gggttcgacc 20340
cctacttcgt ctactcgggc tccatcccct acctagacgg caccttctac ctcaaccaca 20400
ccttcaagaa ggtctccatc accttcgact cctccgtcag ctggcccggc aacgaccgcc 20460
tcctgacgcc caacgagttc gaaatcaagc gcaccgtcga cggagaggga tacaacgtgg 20520
cccagtgcaa catgaccaag gactggttcc tggtccagat gctggcccac tacaacatcg 20580
gctaccaggg cttctacgtg cccgagggct acaaggaccg catgtactcc ttcttccgca 20640
acttccagcc catgagccgc caggtcgtgg acgaggtcaa ctacaaggac taccaggccg 20700
tcaccctggc ctaccagcac aacaactcgg gcttcgtcgg ctacctcgcg cccaccatgc 20760
gccagggcca gccctacccc gccaactacc cctacccgct catcggcaag agcgccgtcg 20820
ccagcgtcac ccagaaaaag ttcctctgcg accgggtcat gtggcgcatc cccttctcca 20880
gcttcctcaa tgcccactcc gcctactttc gctcccaccg cgcgcgcatc gagaaggcca 20940
gcaacttcat gtccatgggc gcgctcaccg acctcggcca gaacatgctc tacgccaact 21000
ccgcccacgc gctagacatg aatttcgaag tcgaccccat ggatgagtcc acccttctct 21060
atgttgtctt cgaagtcttc gacgtcgtcc gagtgcacca gccccaccgc ggcgtcatcg 21120
aagccgtcta cctgcgcacg cccttctcgg ccggcaacgc caccacctaa gccgctcttg 21180
cttcttgcaa gatgacggcg ggctccggcg agcaggagct cagggccatc ctccgcgacc 21240
tgggctgcgg gccctgcttc ctgggcacct tcgacaagcg cttccctgga ttcatggccc 21300
cgcacaagct ggcctgcgcc atcgtgaaca cggccggccg cgagaccggg ggcgagcact 21360
ggctggcctt cgcctggaac ccgcgctccc acacatgcta cctcttcgac cccttcgggt 21420
tctcggacga gcgcctcaag cagatctacc agttcgagta cgagggcctg ctgcgtcgca 21480
gcgccctggc caccgaggac cgctgcgtca ccctggaaaa gtccacccag accgtgcagg 21540
gtccgcgctc ggccgcctgc gggctcttct gctgcatgtt cctgcacgcc ttcgtgcact 21600
ggcccgaccg ccccatggac aagaacccca ccatgaactt actgacgggg gtgcccaacg 21660
gcatgctcca gtcgccccag gtggaaccca ccctgcgccg caaccaggaa gcgctctacc 21720
ccgccttcga ccgcatgaat caagacatgt aaaaaaccgg tgtgtgtatg tgaatgcttt 21780
attcataata aacagcacat gtttatgcca ccttctctga ggctctgact ttatttagaa 21840
atcgaagggg ttctgccggc tctcggcatg gcccgcgggc agggatacgt tgcggaactg 21900
gtacttgggc agccacttga actcggggat cagcagcttg ggcacgggga ggtcggggaa 21960
cgagtcgctc cacagcttgc gcgtgagttg cagggcgccc agcaggtcgg gcgcggagat 22020
cttgaaatcg cagttgggac ccgcgttctg cgcgcgagag ttgcggtaca cggggttgca 22080
gcactggaac accatcaggg ccgggtgctt cacgcttgcc agcaccgtcg cgtcggtgat 22140
gccctccacg tccagatcct cggcgttggc catcccgaag ggggtcatct tgcaggtctg 22200
ccgccccatg ctgggcacgc agccgggctt gtggttgcaa tcgcagtgca gggggatcag 22260
catcatctgg gcctgctcgg agctcatgcc cgggtacatg gccttcatga aagccttcag 22320
ctggcggaag gcctgctgcg ccttgccgcc ctcggtgaag aagaccccgc aggacttgct 22380
agagaactgg ttggtggcgc agccggcgtc gtgcacgcag cagcgcgcgt cgttgttggc 22440
cagctgcacc acgctgcgcc cccagcggtt ctgggtgatc ttggcccggt tggggttctc 22500
cttcagcgcg cgctgcccgt tctcgctcgc cacatccatc tcgatagtgt gctccttctg 22560
gatcatcacg gtcccgtgca ggcaccgcag cttgccctcg gcttcggtgc agccgtgcag 22620
ccacagcgcg cagccggtgc actcccagtt cttgtgggcg atctgggagt gcgagtgcac 22680
gaagccctgc aggaagcggc ccatcatcgc ggtcagggtc ttgttgctgg tgaaggtcag 22740
cgggatgccg cggtgctcct cgttcacata caggtggcag atgcggcggt acacctcgcc 22800
ctgctcgggc atcagctgga aggcggactt caggtcgctc tccacgcggt accggtccat 22860
cagcagcgtc atcacttcca tgcccttctc ccaggccgaa acgatcggca ggctcagggg 22920
gttcttcacc gccattgtca tcttagtcgc cgccgccgag gtcagggggt cgttctcgtc 22980
cagggtctca aacactcgct tgccgtcctt ctcgatgatg cgcacggggg gaaagctgaa 23040
gcccacggcc gccagctcct cctcggcctg cctttcgtcc tcgctgtcct ggctgatgtc 23100
ttgcaaaggc acatgcttgg tcttgcgggg tttctttttg ggcggcagag gcggcggcga 23160
tgtgctggga gagcgcgagt tctcgttcac cacgactatt tcttcttctt ggccgtcgtc 23220
cgagaccacg cggcggtagg catgcctctt ctggggcaga ggcggaggcg acgggctctc 23280
gcggttcggc gggcggctgg cagagcccct tccgcgttcg ggggtgcgct cctggcggcg 23340
ctgctctgac tgacttcctc cgcggccggc cattgtgttc tcctagggag caacaacaag 23400
catggagact cagccatcgt cgccaacatc gccatctgcc cccgccgcca ccgccgacga 23460
gaaccagcag cagaatgaaa gcttaaccgc cccgccgccc agccccacct ccgacgccgc 23520
ggccccagac atgcaagaga tggaggaatc catcgagatt gacctgggct acgtgacgcc 23580
cgcggagcac gaggaggagc tggcagcgcg cttttcagcc ccggaagaga accaccaaga 23640
gcagccagag caggaagcag agaacgagca gaaccaggct gggcacgagc atggcgacta 23700
cctgagcggg gcagaggacg tgctcatcaa gcatctggcc cgccaatgca tcatcgtcaa 23760
ggacgcgctg ctcgaccgcg ccgaggtgcc cctcagcgtg gcggagctca gccgcgccta 23820
cgagcgcaac ctcttctcgc cgcgcgtgcc ccccaagcgc cagcccaacg gcacctgtga 23880
gcccaacccg cgcctcaact tctacccggt cttcgcggtg cccgaggccc tggccaccta 23940
ccacctcttt ttcaagaacc aaaggatccc cgtctcctgc cgcgccaacc gcacccgcgc 24000
cgacgccctg ctcaacctgg gccccggcgc ccgcctacct gatatcacct ccttggaaga 24060
ggttcccaag atcttcgagg gtctgggcag cgacgagact cgggccgcga acgctctgca 24120
aggaagcgga gaggagcatg agcaccacag cgccctggtg gagttggaag gcgacaacgc 24180
gcgcctggcg gtcctcaagc gcacggtcga gctgacccac ttcgcctacc cggcgctcaa 24240
cctgcccccc aaggtcatga gcgccgtcat ggaccaggtg ctcatcaagc gcgcctcgcc 24300
cctctcggag gaggagatgc aggaccccga gagttcggac gagggcaagc ccgtggtcag 24360
cgacgagcag ctggcgcgct ggctgggagc gagtancacc ccccagagcc tggaagagcg 24420
gcgcaagctc atgatggccg tggtcctggt gaccgtggag ctggagtgtc tgcgccgctt 24480
ctttgccgac gcggagaccc tgcgcaaggt cgaggagaac ctgcactacc tcttcaggca 24540
cgggttcgtg cgccaggcct gcaagatctc caacgtggag ctgaccaacc tggtctccta 24600
catgggcatc ctgcacgaga accgcctggg gcaaaacgtg ctgcacacca ccctgcgcgg 24660
ggaggcccgc cgcgactaca tccgcgactg cgtctacctg tacctctgcc acacctggca 24720
gacgggcatg ggcgtgtggc agcagtgcct ggaggagcag aacctgaaag agctctgcaa 24780
gctcctgcag aagaacctca aggccctgtg gaccgggttc gacgagcgta ccaccgcctc 24840
ggacctggcc gacctcatct tccccgagcg cctgcggctg acgctgcgca acgggctgcc 24900
cgactttatg agccaaagca tgttgcaaaa ctttcgctct ttcatcctcg aacgctccgg 24960
gatcctgccc gccacctgct ccgcgctgcc ctcggacttc gtgccgctga ccttccgcga 25020
gtgccccccg ccgctctgga gccactgcta cttgctgcgc ctggccaact acctggccta 25080
ccactcggac gtgatcgagg acgtcagcgg cgagggtctg ctggagtgcc actgccgctg 25140
caacctctgc acgccgcacc gctccctggc ctgcaacccc cagctgctga gcgagaccca 25200
gatcatcggc accttcgagt tgcaaggccc cggcgacggc gagggcaagg ggggtctgaa 25260
actcaccccg gggctgtgga cctcggccta cttgcgcaag ttcgtgcccg aggactacca 25320
tcccttcgag atcaggttct acgaggacca atcccagccg cccaaggccg agctgtcggc 25380
ctgcgtcatc acccaggggg ccatcctggc ccaattgcaa gccatccaga aatcccgcca 25440
agaatttctg ctgaaaaagg gccacggggt ctacttggac ccccagaccg gagaggagct 25500
caaccccagc ttcccccagg atgccccgag gaagcagcaa gaagctgaaa gtggagctgc 25560
cgccgccgga ggatttggag gaagactggg agagcagtca ggcagaggag gaggagatgg 25620
aagactggga cagcactcag gcagaggagg acagcctgca agacagtctg gaggaggaag 25680
acgaggtgga ggaggcagag gaagaagcag ccgccgccag accgtcgtcc tcggcggaga 25740
aagcaagcag cacggatacc atctccgctc cgggtcgggg tcgcggcggc cgggcccaca 25800
gtaggtggga cgagaccggg cgcttccgaa ccccaccacc cagaccggta agaaggagcg 25860
gcagggatac aagtcctggc gggggcacaa aaacgccatc gtctcctgct tgcaagcctg 25920
cgggggcaac atctccttca cccggcgcta cctgctcttt caccgcgggg tgaacttccc 25980
ccgcaacatc ttgcattact accgtcacct ccacagcccc tactactgtt tccaagaaga 26040
ggcagaaacc cagcagcagc agaaaaccag cggcagcagc agctagaaaa tccacagcgg 26100
cggcaggtgg actgaggatc gcggcgaacg agccggcgca gacccgggag ctgaggaacc 26160
ggatctttcc caccctctat gccatcttcc agcagagtcg ggggcaggag caggaactga 26220
aagtcaagaa ccgttctctg cgctcgctca cccgcagttg tctgtatcac aagagcgaag 26280
accaacttca gcgcactctc gaggacgccg aggctctctt caacaagtac tgcgcgctca 26340
ctcttaaaga gtagcccgcg cccgcccaca cacggaaaaa ggcgggaatt acgtcaccac 26400
ctgcgccctt cgcccgacca tcatgagcaa agagattccc acgccttaca tgtggagcta 26460
ccagccccag atgggcctgg ccgccggcgc cgcccaggac tactccaccc gcatgaactg 26520
gctcagtgcc gggcccgcga tgatctcacg ggtgaatgac atccgcgccc accgaaacca 26580
gatactccta gaacagtcag cgatcaccgc cacgccccgc catcacctta atccgcgtaa 26640
ttggcccgcc gccctggtgt accaggaaat tccccagccc acgaccgtac tacttccgcg 26700
agacgcccag gccgaagtcc agctgactaa ctcaggtgtc cagctggccg gcggcgccgc 26760
cctgtgtcgt caccgccccg ctcagggtat aaagcggctg gtgatccgag gcagaggcac 26820
acagctcaac gacgaggtgg tgagctcttc gctgggtctg cgacctgacg gagtcttcca 26880
actcgccgga tcggggagat cttccttcac gcctcgtcag gccgtcctga ctttggagag 26940
ttcgtcctcg cagccccgct cgggcggcat cggcactctc cagttcgtgg aggagttcac 27000
tccctcggtn tacttcaacc ccttctccgg ctcccccggc cactacccgg acgagttcat 27060
cccgaacttc gacgccatca gcgagtcggt ggacggctac gattgaatgt cccatggtgg 27120
cgcagctgac ctagctcggc ttcgacacct ggaccactgc cgccgcttcc gctgcttcgc 27180
tcgggatctc gccgagtttg cctactttga gctgcccgag gagcaccctc agggcccagc 27240
ccacggagtg cggatcatcg tcgaaggggg cctcgactcc cacctgcttc ggatcttcag 27300
ccagcgaccg atcctggtcg agcgcgaaca aggacagacc cttcttactt tgtactgcat 27360
ctgcaaccac cccggcctgc atgaaagtct ttgttgtctg ctgtgtactg agtataataa 27420
aagctgagat cagcgactac tccggactcg attgtggtgt tcctgctatc aaccggtccc 27480
tgttcttcac cgggaacgag accgagctcc agctccagtg taagccccac aagaagtacc 27540
tcacctggct gttccagggc tccccgatcg ccgttgtcaa ccactgcgac aacgacggag 27600
tcctgctgag cggccctgcc aaccttactt tttccacccg cagaagcaag ctccagctct 27660
tccaaccctt cctccccggg acctatcagt gcgtctcagg accctgccat cacaccttcc 27720
acctgatccc gaataccaca gcgccgctcc ccgctactaa caaccaaact acccaccaac 27780
gccaccgtcg cgacctttcc tctgaatcta ataccactac cggaggtgag ctccgaggtc 27840
gaccaacctc tgggatttac tacggcccct gggaggtggt ggggttaata gcgctaggcc 27900
tagttgcggg tgggcttttg gttctctgct acctatacct cccttgctgt tcgtacttag 27960
tggtgctgtg ttgctggttt aagaaatggg gaagatcacc ctagtgagct gcggtgcgct 28020
ggtggcggtg ttgctttcga ttgtgggact gggcggcgcg gctgtagtga aggagaaggc 28080
cgatccctgc ttgcatttca atcccaacaa atgccagctg agttttcagc ccgatggcaa 28140
tcggtgcgcg gtactgatca agtgcggatg ggaatgcgag aacgtgagaa tcgagtacaa 28200
taacaagact cggaacaata ctctcgcgtc cgtgtggcag cccggggacc ccgagtggta 28260
caccgtctct gtccccggtg ctgacggctc cccgcgcacc gtgaataata ctttcatttt 28320
tgcgcacatg tgcaacacgg tcatgtggat gagcaagcag tacgatatgt ggccccccac 28380
gaaggagaac atcgtggtct tctccatcgc ttacagcctg tgcacggcgc taatcaccgc 28440
tatcgtgtgc ctgagcattc acatgctcat cgctattcgc cccagaaata atgccgagaa 28500
agagaaacag ccataacacg ttttttcaca caccttgttt ttacagacaa tgcgtctgtt 28560
aaatttttta aacattgtgc tcagtattgc ttatgcctct ggttatgcaa acatacagaa 28620
aaccctttat gtaggatctg atggtacact agagngtacc caatcacaag ccaaggttgc 28680
atggtatttt tatagaacca acactgatcc agttaaactt tgtaagggtg aattgccgcg 28740
tacacataaa actccactta catttagttg cagcaataat aatcttacac ttttttcaat 28800
tacaaaacaa tatactggta cttattacag tacaaacttt catacaggac aagataaata 28860
ttatactgtt aaggtagaaa atcctaccac tcctagaact accaccacca ccactactgc 28920
aaagcccact gtgaaaacta caactaggac caccacaact acagaaacca ccaccagcac 28980
aacacttgct gcaactacac acacacacac taagctaacc ttacagacca ctaatgattt 29040
gatcgccctg ctgcaaaagg gggataacag caccacttcc aatgaggaga tacccaaatc 29100
catgattggc attattgttg ctgtagtggt gtgcatgttg atcatcgcct tgtgcatggt 29160
gtactatgcc ttctgctaca gaaagcacag actgaacgac aagctggaac acttactaag 29220
tgttgaattt taatttttta gaaccatgaa gatcctaggc ctttttagtt tttctatcat 29280
tacctctgct ctttgtgaat cagtggatag agatgttact attaccactg gttctaatta 29340
tacactgaaa gggccaccct caggtatgct ttcgtggtat tgctattttg gaactgacac 29400
tgatcaaact gaattatgca attttcaaaa aggcaaaacc tcaaactcta aaatctctaa 29460
ttatcaatgc aatggcactg atctgatact actcaatgtc acgaaagcat atggtggcag 29520
ttattattgc cctggacaaa acactgaaga aatgattttt tacaaagtgg aagtggttga 29580
tcccactaca ccacccacca ccacaactat tcataccaca cacacagaac aaacaccaga 29640
ggcaacagaa gcagagttgg ccttccaggt tcacggagat tcctttgctg tcaatacccc 29700
tacacccgat cagcggtgtc cggggccgct agtcagcggc attgtcggtg tgctttcggg 29760
attagcagtc ataatcatct gcatgttcat ttttgcttgc tgctatagaa ggctttaccg 29820
acaaaaatca gacccactgc tgaacctcta tgtttaattt tttccagagc catgaaggca 29880
gttagcgctc tagttttttg ttctttgatt ggcattgttt ttaatagtaa aattaccaga 29940
gttagcttta ttaaacatgt taatgtaact gaaggagata acatcacact agcaggtgta 30000
gaaggtgctc aaaacaccac ctggacaaaa taccatctag gatggagaga tatttgcacc 30060
tggaatgtaa cttattattg cataggagtt aatcttacca ttgttaacgc taaccaatct 30120
cagaatgggt taattaaagg acagagtgtt agtgtgacca gtgatgggta ctatacccag 30180
catagtttta actacaacat tactgtcata ccactgccta cgcctagccc acctagcact 30240
accacacaga caaccacata cagtacatca aatcagccta ccaccactac agcagcagag 30300
gttgccagct cgtctggggt ccgagtggca tttttgatgt tggccccatc tagcagtccc 30360
actgctagta ccaatgagca gactactgaa tttttgtcca ctgtcgagag ccacaccaca 30420
gctacctcca gtgccttctc tagcaccgcc aatctctcct cgctttcctc tacaccaatc 30480
agccccgcta ctactcctag ccccgctcct cttcccactc ccctgaagca aacagacggc 30540
ggcatgcaat ggcagatcac cctgctcatt gtgatcgggt tggtcatcct ggccgtgttg 30600
ctctactaca tcttctgccg ccgcattccc aacgcgcacc gcaagccggc ctacaagccc 30660
atcgttatcg ggcagccgga gccgcttcag gtggaagggg gtctaaggaa tcttctcttc 30720
tcttttacag tatggtgatt gaantatgat tcctagacaa ttcttgatca ctattcttat 30780
ctgcctcctc caagtctgtg ccaccctcgc tctggtggcc aacgccagtc cagactgtat 30840
tgggcccttc gcctcctacg tgctctttgc cttcgtcacc tgcatctgct gctgtagcat 30900
agtctgcctg cttatcacct tcttccagtt cattgactgg atctttgtgc gcatcgccta 30960
cctgcgccac cacccccagt accgcgacca gcgagtggcg cagctgctca ggctcctctg 31020
ataagcatgc gggctctgct acttntcgcg cttctgctgt tagtgctccc ccgtcccgtc 31080
gacccccggt cccccactca gtcccccgag gaggttcgca aatgcaaatt ccaagaaccc 31140
tggaaattcc tcaaatgcta ccgccaaaaa tcagacatgc atcccagctg gatcatgatc 31200
attgggatcg tgaacattct ggcctgcacc ctcatctcct ttgtgattta cccctgcttt 31260
gactttggtt ggaactcgcc agaggcgctc tatctcccgc ctgaacctga cacaccacca 31320
cagcatcaac ctcaggcaca cgcactacca ccaccacagc ctaggccaca atacatgccc 31380
atattagact atgaggccga gccacagcga cccatgctcc ccgctattag ttacttcaat 31440
ctaaccggcg gagatgactg acccactggc caataacaac gtcaacgacc ttctcctgga 31500
catggacggc cgcgcctcgg agcagcgact cgcccaactt cgcattcgtc agcagcagga 31560
gagagccgtc aaggagctgc aggacggcat agccatccac cagtgcaaga gaggcatctt 31620
ctgcctggtg aaacaggcca agatctccta cgaggtcacc cagaccgacc atcgcctctc 31680
ctacgagctc ctgcagcagc gccagaagtt cacctgcctg gtcggagtca accccatcgt 31740
catcacccag ccagcagtcg ggcgatacca aggggtgcat ccactgctcc tgcgactccc 31800
ccgactgcgt ccacactctg atcaagaccc tctgcggcct ccgcgacctc ctccccatga 31860
actaatcacc cccttatcca gtgaaataaa gatcatattg atgatgattt aaataaaaaa 31920
aataatcatt tgatttgaaa taaagataca atcatattga tgatttgagt ttaacaaaaa 31980
taaagaatca cttacttgaa atctgatacc aggtctctgt ccatgttttc tgccaacacc 32040
acctcactcc cctcttccca gctctggtac tgcaggcccc ggcgggctgc aaacttcctc 32100
cacacgctga aggggatgtc aaattcctcc tgtccctcaa tcttcatttt atcttctatc 32160
agatgtccaa aaagcgcgtc cgggtggatg atgacttcga ccccgtctac ccctacgatg 32220
cagacaacgc accgaccgtg cccttcatca accccccctt cgtctcttca gatggattcc 32280
aagagaagcc cctgggggtg ttgtccctgc gactggctga ccccgtcacc accaagaacg 32340
gggaaatcac cctcaagctg ggagaggggg tggacctcga ctcgtcggga aaactcatct 32400
ccaacacggc caccaaggcc gccgcccctc tcagtatttc aaacaacacc atttccctta 32460
aaactgctgc ccctttctac aacaacaatg gaactttaag cctcaatgtc tccacaccat 32520
tagcagtatt tcccacattt aacactttag gcataagtct tggaaacggt cttcagactt 32580
caaataagtt gttgactgta caactaactc atcctcttac attcagctca aatagcatca 32640
cagtaaaaac agacaaaggg ctatatatta actccagtgg aaacagagga cttgaggcta 32700
atataagcct aaaaagagga ctagtttttg acggtaatgc tattgcaaca tatattggaa 32760
atggcttaga ctatggatct tatgatagtg atggaaaaac aagacccgta attaccaaaa 32820
ttggagcagg attaaatttt gatgctaaca aagcaatagc tgtcaaacta ggcacaggtt 32880
taagttttga ctccgctggt gccttgacag ctggaaacaa acaggatgac aagctaacac 32940
tttggactac ccctgaccca agccctaatt gtcaattact ttcagacaga gatgccaaat 33000
ttactctctg tcttacaaaa tgcggtagtc aaatactagg cactgtggca gtggcggctg 33060
ttactgtagg atcagcacta aatccaatta atgacacagt caaaagcgcc atagttttcc 33120
ttagatttga ttccgatggt gtactcatgt caaactcatc aatggtaggt gattactgga 33180
actttaggga gggacagacc actcaaagtg tagcctatac aaatgctgtg ggattcatgc 33240
caaatatagg tgcatatcca aaaacccaaa gtaaaacacc taaaaatagc atagtcagtc 33300
aggtatattt aactggagaa actactatgc caatgacact aaccataact ttcaatggca 33360
ctgatgaaaa agacacaacc ccagttagca cctactctat gacttttaca tggcagtgga 33420
ctggagacta taaggacaaa aatattacct ttgctaccaa ctcattctct ttttcctaca 33480
tcgcccagga ataatcccac ccagcaagcc aacccctttt cccaccacct ttgtctatat 33540
ggaaactctg aaacagaaaa ataaagttca agtgttttat tgaatcaaca gttttacagg 33600
actcgagcag ttatttttcc tccaccctcc caggacatgg aatacaccac cctctccccc 33660
cgcacagcct tgaacatctg aatgccattg gtgatggaca tgcttttggt ctccacgttc 33720
cacacagttt cagagcgagc cagtctcgga tcggtcaggg agatgaaacc ctccgggcac 33780
tcccgcatct gcacctcaca gctcaacagc tgaggattgt cctcggtggt cgggatcacg 33840
gttatctgga agaagcagaa gagcggcggt gggaatcata gtccgcgaac gggatcggcc 33900
ggtggtgtcg catcaggccc cgcagcagtc gctgccgccg ccgctccgtc aagctgctgc 33960
tcagggggtt cgggtccagg gactccctca gcatgatgcc cacggccctc agcatcagtc 34020
gtctggtgcg gcgggcgcag cagcgcatgc gaatctcgct caggtcactg cagtacgtgc 34080
aacacaggac caccaggttg ttcaacagtc catagttcaa cacgctccag ccgaaactca 34140
tcgcgggaag gatgctaccc acgtggccgt cgtaccagat cctcaggtaa atcaagtggc 34200
gctccctcca gaagacgctg cccatgtaca tgatctcctt gggcatgtgg cggttcacca 34260
cctcccggta ccacatcacc ctctggttga acatgcagcc ccggatgatc ctgcggaacc 34320
acagggccag caccgccccg cccgccatgc agcgaagaga ccccggatcc cggcaatgac 34380
aatggaggac ccaccgctcg tacccgtgga tcatctggga gctgaacaag tctatgttgg 34440
cacagcacag gcatatgctc atgcatctct tcagcactct cagctcctcg ggggtcaaaa 34500
ccatatccca gggcacgggg aactcttgca ggacagcgaa ccccgcagaa cagggcaatc 34560
ctcgcacata acttacattg tgcatggaca gggtatcgca atcaggcagc accgggtgat 34620
cctccaccag agaagcgcgg gtctcggtct cctcacagcg tggtaagggg gccggccgat 34680
acgggtgatg gcgggacgcg gctgatcgtg ttctcgaccg tgtcatgatg cagttgcttt 34740
cggacatttt cgtacttgct gtagcagaac ctggtccggg cgctgcacac cgatcgccgg 34800
cggcggtctc ggcgcttgga acgctcggtg ttaaagttgt aaaacagcca ctctctcaga 34860
ccgtgcagca gatctagggc ctcaggagtg atgaagatcc catcatgcct gatagctctg 34920
atcacatcga ccaccgtgga atgggccagg cccagccaga tgatgcaatt ttgttgggtt 34980
tcggtgacgg cgggggaggg aagaacagga agaaccatga ttaactttta atccaaacgg 35040
tctcggagca cttcaaaatg aaggtcacgg agatggcacc tctcgccccc gctgtgttgg 35100
tggaaaataa cagccaggtc aaaggtgata cggttctcga gatgttccac ggtggcttcc 35160
agcaaagcct ccacgcgcac atcagaaaca agacaatagc gaaagcggga gggttctcta 35220
attcctcaac catcatgtta cactcctgca ccatccccag ataattttca tttttccagc 35280
cttgaatgat tcgaactagt tcctgaggta aatccaagcc agccatgata aaaagctcgc 35340
gcagagcacc ctccaccggc attcttaagc acaccctcat aattccaaga tattctgctc 35400
ctggttcacc tgcagcagat tgacaagcgg aatatcaaaa tctctgccgc gatccctgag 35460
ctcctccctc agcaataact gtaagtactc tttcatatcg tctccgaaat ttttagccat 35520
aggaccccca ggaataagag aagggcaagc cacattacag ataaaccgaa gtccccccca 35580
gtgagcattg ccaaatgtaa gattgaaata agcatgctgg ctagacccgg tgatatcttc 35640
cagataactg gacagaaaat cgggtaagca atttttaaga aaatcaacaa aagaaaaatc 35700
ttccaggtgc acgtttaggg cctcgggaac aacgatggag taagtgcaag gggtgcgttc 35760
cagcatggtt agttagctga tctgtaaaaa aacaaaaaat aaaacattaa accatgctag 35820
cctggcgaac aggtgggtaa atcgttctct ccagcaccag gcaggccacg gggtctccgg 35880
cgcgaccctc gtaaaaattg tcgctatgat tgaaaaccat cacagagaga cgttcccggt 35940
ggccggcgtg aatgattcga gaagaagcat acaccccccg gaacattgga gtccgtgagt 36000
gaaaaaaagc ggccgaggaa gcaatgaggc actacaacgc tcactctcaa gtccagcaaa 36060
gcgatgccat gcggatgaag cacaaaattt tcaggtgcgt aaaaaatgta attactcccc 36120
tcctgcacag gcagcgaagc tcccgatccc tccagataca catacaaagc ctcagcgtcc 36180
atagcttacc gagcggcagc agcagcggca cacaacaggc gcaagagtca gagaaaagac 36240
tgagctctaa cctgtccgcc cgctctctgc tcaatatata gccccagatc tacactgacg 36300
taaaggccaa agtctaaaaa tacccgccaa ataatcacac acgcccagca cacgcccaga 36360
aaccggtgac acactcagaa aaatacgcgc acttcctcaa acggccaaac tgccgtcatt 36420
tccgggttcc cacgctacgt catcaaaaca cgactttcaa attccgtcga ccgttaaaaa 36480
catcacccgc cccgccccta acggtcgccg ctcccgcagc caatcacctt cctccctccc 36540
caaattcaaa cagctcattt gcatattaac gcgcaccaaa agtttgaggt atattattga 36600
tgatgg 36606
<210> 4
<211> 36535
<212> DNA
<213> 黑猩猩Pan 7 (CV33)基因组
<400> 4
catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg agctgtttga 60
atttggggag ggaggaaggt gattggccga gagacgggcg accgttaggg gcggggcggg 120
tgacgttttg atgacgtggc cgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180
gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240
ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300
aatgaggaag tgaaaatctg agtaatttcg cgtttatggc agggaggagt atttgccgag 360
ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420
ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggc gtcagctgat cgccagggta 480
tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540
cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600
gtaatgtttt cctggctact gggaacgaga ttctggaatt ggtggtggac gccatgatgg 660
gtggcgaccc tcctgagccc cctaccccat ttgaggcgcc ttcgctgtac gatttgtatg 720
atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780
gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840
cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900
aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960
aggaggcgat tcgagctgca tcgaaccagg gagtgaaagc tgcgggcgaa agctttagcc 1020
tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080
ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140
acagtaagtg tgattaactt tagttgggaa ggcagagggt gactgggtgc tgactggttt 1200
atttatgtat atgttttttt atgtgtaggt cccgtctctg acgtagatga gacccccact 1260
tcagagtgca tttcatcacc cccagaaatt ggcgaggaac cgcccgaaga tattattcat 1320
agaccagttg cagtgagagt caccgggcgg agagcagctg tggagagttt ggatgacttg 1380
ctacagggtg gggatgaacc tttggacttg tgtacccgga aacgccccag gcactaagtg 1440
ccacacatgt gtgtttactt aaggtgatgt cagtatttat agggtgtgga gtgcaataaa 1500
atccgtgttg actttaagtg cgtggtttat gactcagggg tggggactgt gggtatataa 1560
gcaggtgcag acctgtgtgg tcagttcaga gcaggactca tggagatctg gacggtcttg 1620
gaagactttc accagactag acagctgcta gagaactcat cggagggggt ctcttacctg 1680
tggagattct gcttcggtgg gcctctagct aagctagtct atagggccaa acaggattat 1740
aaggatcaat ttgaggatat tttgagagag tgtcctggta tttttgactc tctcaacttg 1800
ggccatcagt ctcactttaa ccagagtatt ctgagagccc ttgacttttc tactcctggc 1860
agaactaccg ccgcggtagc cttttttgcc tttatccttg acaaatggag tcaagaaacc 1920
catttcagca gggattaccg tctggactgc ttagcagtag ctttgtggag aacatggagg 1980
tgccagcgcc tgaatgcaat ctccggctac ttgccagtac agccggtaga cacgctgagg 2040
atcctgagtc tccagtcacc ccaggaacac caacgccgcc agcagccgca gcaggagcag 2100
cagcaagagg aggaggagga tcgagaagag aacccgagag ccggtctgga ccctccggtg 2160
gcggaggagg aggagtagct gacttgtttc ccgagctgcg ccgggtgctg actaggtctt 2220
ccagtggacg ggagaggggg attaagcggg agaggcatga ggagactagc cacagaactg 2280
aactgactgt cagtctgatg agccgcaggc gcccagaatc ggtgtggtgg catgaggttc 2340
agtcgcaggg gatagatgag gtctcggtga tgcatgagaa atattccctg gaacaagtca 2400
agacttgttg gttggagcct gaggatgatt gggaggtagc catcaggaat tatgccaagc 2460
tggctctgaa gccagacaag aagtacaaga ttaccaaact gattaatatc agaaattcct 2520
gctacatttc agggaatggg gccgaggtgg agatcagtac ccaggagagg gtggccttca 2580
gatgttgtat gatgaatatg tacccggggg tggtgggcat ggagggagtc acctttatga 2640
acgcgaggtt caggggtgat gggtataatg gggtggtctt tatggccaac accaagctga 2700
cagtgcacgg atgctccttc tttgggttca ataacatgtg catcgaggcc tggggcagtg 2760
tttcagtgag gggatgcagc ttttcagcca actggatggg ggtcgtgggc agaaccaaga 2820
gcaaggtgtc agtgaagaaa tgcctgttcg agaggtgcca cctgggggtg atgagcgagg 2880
gcgaagccaa agtcaaacac tgcgcctcta ctgagacggg ctgctttgtg ctgatcaagg 2940
gcaatgccca agtcaagcat aacatgatct gtggggcctc ggatgagcgc ggctaccaga 3000
tgctgacctg cgccggtggg aacagccata tgctggccac cgtgcatgtg acctcgcacc 3060
cccgcaagac atggcccgag ttcgagcaca acgtcatgac ccgatgcaat gtgcacctgg 3120
ggtcccgccg aggcatgttc atgccctacc agtgcaacat gcaatttgtg aaggtgctgc 3180
tggagcccga tgccatgtcc agagtgagcc tgacgggggt gtttgacatg aatgtggagc 3240
tgtggaaaat tctgagatat gatgaatcca agaccaggtg ccgggcctgc gaatgcggag 3300
gcaagcacgc caggcttcag cccgtgtgtg tggaggtgac ggaggacctg cgacccgatc 3360
atttggtgtt gtcctgcaac gggacggagt tcggctccag cggggaagaa tctgactaga 3420
gtgagtagtg tttgggggag gtggagggct tgtatgaggg gcagaatgac taaaatctgt 3480
gtttttctgt gtgttgcagc agcatgagcg gaagcgcctc ctttgaggga ggggtattca 3540
gcccttatct gacggggcgt ctcccctcct gggcgggagt gcgtcagaat gtgatgggat 3600
ccacggtgga cggccggccc gtgcagcccg cgaactcttc aaccctgacc tacgcgaccc 3660
tgagctcctc gtccgtggac gcagctgccg ccgcagctgc tgcttccgcc gccagcgccg 3720
tgcgcggaat ggccctgggc gccggctact acagctctct ggtggccaac tcgacttcca 3780
ccaataatcc cgccagcctg aacgaggaga agctgctgct gctgatggcc cagctcgagg 3840
ccctgaccca gcgcctgggc gagctgaccc agcaggtggc tcagctgcag gcggagacgc 3900
gggccgcggt tgccacggtg aaaaccaaat aaaaaatgaa tcaataaata aacggagacg 3960
gttgttgatt ttaacacaga gtcttgaatc tttatttgat ttttcgcgcg cggtaggccc 4020
tggaccaccg gtctcgatca ttgagcaccc ggtggatttt ttccaggacc cggtagaggt 4080
gggcttggat gttgaggtac atgggcatga gcccgtcccg ggggtggagg tagctccatt 4140
gcagggcctc gtgctcgggg gtggtgttgt aaatcaccca gtcatagcag gggcgcaggg 4200
cgtggtgctg cacgatgtcc ttgaggagga gactgatggc cacgggcagc cccttggtgt 4260
aggtgttgac gaacctgttg agctgggagg gatgcatgcg gggggagatg agatgcatct 4320
tggcctggat cttgagattg gcgatgttcc cgcccagatc ccgccggggg ttcatgttgt 4380
gcaggaccac cagcacggtg tatccggtgc acttggggaa tttgtcatgc aacttggaag 4440
ggaaggcgtg aaagaatttg gagacgccct tgtgaccgcc caggttttcc atgcactcat 4500
ccatgatgat ggcgatgggc ccgtgggcgg cggcctgggc aaagacgttt cgggggtcgg 4560
acacatcgta gttgtggtcc tgggtgagct cgtcataggc cattttaatg aatttggggc 4620
ggagggtgcc cgactggggg acgaaggtgc cctcgatccc gggggcgtag ttgccctcgc 4680
agatctgcat ctcccaggcc ttgagctcgg agggggggat catgtccacc tgcggggcga 4740
tgaaaaaaac ggtttccggg gcgggggaga tgagctgggc cgaaagcagg ttccggagca 4800
gctgggactt gccgcagccg gtggggccgt agatgacccc gatgaccggc tgcaggtggt 4860
agttgaggga gagacagctg ccgtcctcgc ggaggagggg ggccacctcg ttcatcatct 4920
cgcgcacatg catgttctcg cgcacgagtt ccgccaggag gcgctcgccc cccagcgaga 4980
ggagctcttg cagcgaggcg aagtttttca gcggcttgag cccgtcggcc atgggcattt 5040
tggagagggt ctgttgcaag agttccagac ggtcccagag ctcggtgatg tgctctaggg 5100
catctcgatc cagcagacct cctcgtttcg cgggttgggg cgactgcggg agtagggcac 5160
caggcgatgg gcgtccagcg aggccagggt ccggtccttc cagggtcgca gggtccgcgt 5220
cagcgtggtc tccgtcacgg tgaaggggtg cgcgccgggc tgggcgcttg cgagggtgcg 5280
cttcaggctc atccggctgg tcgagaaccg ctcccggtcg gcgccctgcg cgtcggccag 5340
gtagcaattg agcatgagtt cgtagttgag cgcctcggcc gcgtggccct tggcgcggag 5400
cttacctttg gaagtgtgtc cgcagacggg acagaggagg gacttgaggg cgtagagctt 5460
gggggcgagg aagacggact cgggggcgta ggcgtccgcg ccgcagctgg cgcagacggt 5520
ctcgcactcc acgagccagg tgaggtcggg ccggttgggg tcaaaaacga ggtttcctcc 5580
gtgctttttg atgcgtttct tacctctggt ctccatgagc tcgtgtcccc gctgggtgac 5640
aaagaggctg tccgtgtccc cgtagaccga ctttatgggc cggtcctcga gcggggtgcc 5700
gcggtcctcg tcgtagagga accccgccca ctccgagacg aaggcccggg tccaggccag 5760
cacgaaggag gccacgtggg aggggtagcg gtcgttgtcc accagcgggt ccaccttctc 5820
cagggtatgc aagcacatgt ccccctcgtc cacatccagg aaggtgattg gcttgtaagt 5880
gtaggccacg tgaccggggg tcccggccgg gggggtataa aagggggcgg gcccctgctc 5940
gtcctcactg tcttccggat cgctgtccag gagcgccagc tgttggggta ggtattccct 6000
ctcgaaggct ggcataacct cggcactcag gttgtcagtt tctagaaacg aggaggattt 6060
gatattgacg gtgccgttgg agacgccttt catgagcccc tcgtccatct ggtcagaaaa 6120
gacgatcttt ttgttgtcga gcttggtggc gaaggagccg tagagggcgt tggagaggag 6180
cttggcgatg gagcgcatgg tctggttctt ttccttgtcg gcgcgctcct tggcggcgat 6240
gttgagctgc acgtactcgc gcgccacgca cttccattcg gggaagacgg tggtgagctc 6300
gtcgggcacg attctgaccc gccagccgcg gttgtgcagg gtgatgaggt ccacgctggt 6360
ggccacctcg ccgcgcaggg gctcgttggt ccagcagagg cgcccgccct tgcgcgagca 6420
gaaggggggc agcgggtcca gcatgagctc gtcggggggg tcggcgtcca cggtgaagat 6480
gccgggcaga agctcggggt cgaagtagct gatgcaggtg tccagatcgt ccagcgccgc 6540
ttgccagtcg cgcacggcca gcgcgcgctc gtaggggctg aggggcgtgc cccagggcat 6600
ggggtgcgtg agcgcggagg cgtacatgcc gcagatgtcg tagacgtaga ggggctcctc 6660
gaggacgccg atgtaggtgg ggtagcagcg ccccccgcgg atgctggcgc gcacgtagtc 6720
gtacagctcg tgcgagggcg cgaggagccc cgtgccgagg ttggagcgtt gcggcttttc 6780
ggcgcggtag acgatctggc ggaagatggc gtgggagttg gaggagatgg tgggcctctg 6840
gaagatgttg aagtgggcgt ggggcaggcc gaccgagtcc ctgatgaagt gggcgtagga 6900
gtcctgcagc ttggcgacga gctcggcggt gacgaggacg tccagggcgc agtagtcgag 6960
ggtctcttgg atgatgtcgt acttgagctg gcccttctgc ttccacagct cgcggttgag 7020
aaggaactct tcgcggtcct tccagtactc ttcgaggggg aacccgtcct gatcggcacg 7080
gtaagagccc accatgtaga actggttgac ggccttgtag gcgcagcagc ccttctccac 7140
ggggagggcg taagcttgtg cggccttgcg cagggaggtg tgggtgaggg cgaaggtgtc 7200
gcgcaccatg accttgagga actggtgctt gaagtcgagg tcgtcgcagc cgccctgctc 7260
ccagagctgg aagtccgtgc gcttcttgta ggcggggttg ggcaaagcga aagtaacatc 7320
gttgaagagg atcttgcccg cgcggggcat gaagttgcga gtgatgcgga aaggctgggg 7380
cacctcggcc cggttgttga tgacctgggc ggcgaggacg atctcgtcga agccgttgat 7440
gttgtgcccg acgatgtaga gttccacgaa tcgcgggcgg cccttaacgt ggggcagctt 7500
cttgagctcg tcgtaggtga gctcggcggg gtcgctgagc ccgtgctgct cgagggccca 7560
gtcggcgacg tgggggttgg cgctgaggaa ggaagtccag agatccacgg ccagggcggt 7620
ctgcaagcgg tcccggtact gacggaactg ctggcccacg gccatttttt cgggggtgac 7680
gcagtagaag gtgcgggggt cgccgtgcca gcggtcccac ttgagctgga gggcgaggtc 7740
gtgggcgagc tcgacgagcg gcgggtcccc ggagagtttc atgaccagca tgaaggggac 7800
gagctgcttg ccgaaggacc ccatccaggt gtaggtttcc acatcgtagg tgaggaagag 7860
cctttcggtg cgaggatgcg agccgatggg gaagaactgg atctcctgcc accagttgga 7920
ggaatggctg ttgatgtgat ggaagtagaa atgccgacgg cgcgccgagc actcgtgctt 7980
gtgtttatac aagcgtccgc agtgctcgca acgctgcacg ggatgcacgt gctgcacgag 8040
ctgtacctgg gttcctttga cgaggaattt cagtgggcag tggagcgctg gcggctgcat 8100
ctggtgctgt actacgtcct ggccatcggc gtggccatcg tctgcctcga tggtggtcat 8160
gctgacgagc ccgcgcggga ggcaggtcca gacttcggct cggacgggtc ggagagcgag 8220
gacgagggcg cgcaggccgg agctgtccag ggtcctgaga cgctgcggag tcaggtcagt 8280
gggcagcggc ggcgcgcggt tgacttgcag gagcttttcc agggcgcgcg ggaggtccag 8340
atggtacttg atctccacgg cgccgttggt ggcgacgtcc acggcttgca gggtcccgtg 8400
cccctggggc gccaccaccg tgccccgttt cttcttgggc gctgcttcca tgccggtcag 8460
aagcggcggc gaggacgcgc gccgggcggc aggggcggct cgggacccgg aggcaggggc 8520
ggcaggggca cgtcggcgcc gcgcgcgggc aggttctggt actgcgcccg gagaagactg 8580
gcgtgagcga cgacgcgacg gttgacgtcc tggatctgac gcctctgggt gaaggccacg 8640
ggacccgtga gtttgaacct gaaagagagt tcgacagaat caatctcggt atcgttgacg 8700
gcggcctgcc gcaggatctc ttgcacgtcg cccgagttgt cctggtaggc gatctcggtc 8760
atgaactgct cgatctcctc ctcctgaagg tctccgcggc cggcgcgctc gacggtggcc 8820
gcgaggtcgt tggagatgcg gcccatgagc tgcgagaagg cgttcatgcc ggcctcgttc 8880
cagacgcggc tgtagaccac ggctccgtcg gggtcgcgcg cgcgcatgac cacctgggcg 8940
aggttgagct cgacgtggcg cgtgaagacc gcgtagttgc agaggcgctg gtagaggtag 9000
ttgagcgtgg tggcgatgtg ctcggtgacg aagaagtaca tgatccagcg gcggagcggc 9060
atctcgctga cgtcgcccag ggcttccaag cgctccatgg cctcgtagaa gtccacggcg 9120
aagttgaaaa actgggagtt gcgcgccgag acggtcaact cctcctccag aagacggatg 9180
agctcagcga tggtggcgcg cacctcgcgc tcgaaggccc cggggggctc ctcttcttcc 9240
atctcttcct cctccactaa catctcttct acttcctcct caggaggcgg cggcggggga 9300
ggggccctgc gtcgccggcg gcgcacgggc agacggtcga tgaagcgctc gatggtctcc 9360
ccgcgccggc gacgcatggt ctcggtgacg gcgcgcccgt cctcgcgggg ccgcagcgtg 9420
aagacgccgc cgcgcatctc caggtggccg ccgggggggt ctccgttggg cagggagagg 9480
gcgctgacga tgcatcttat caattggccc gtagggactc cgcgcaagga cctgagcgtc 9540
tcgagatcca cgggatccga aaaccgctga acgaaggctt cgagccagtc gcagtcgcaa 9600
ggtaggctga gcccggtttc ttgttcttcg gggatttcgg gaggcgggcg ggcgatgctg 9660
ctggtgatga agttgaagta ggcggtcctg agacggcgga tggtggcgag gagcaccagg 9720
tccttgggcc cggcttgctg gatgcgcaga cggtcggcca tgccccaggc gtggtcctga 9780
cacctggcga ggtccttgta gtagtcctgc atgagccgct ccacgggcac ctcctcctcg 9840
cccgcgcggc cgtgcatgcg cgtgagcccg aacccgcgct ggggctggac gagcgccagg 9900
tcggcgacga cgcgctcggc gaggatggcc tgctgtatct gggtgagggt ggtctggaag 9960
tcgtcgaagt cgacgaagcg gtggtaggct ccggtgttga tggtatagga gcagttggcc 10020
atgacggacc agttgacggt ctggtggccg ggtcgcacga gctcgtggta cttgaggcgc 10080
gagtaggcgc gcgtgtcgaa gatgtagtcg ttgcaggtgc gcacgaggta ctggtatccg 10140
acgaggaagt gcggcggcgg ctggcggtag agcggccatc gctcggtggc gggggcgccg 10200
ggcgcgaggt cctcgagcat gaggcggtgg tagccgtaga tgtacctgga catccaggtg 10260
atgccggcgg cggtggtgga ggcgcgcggg aactcgcgga cgcggttcca gatgttgcgc 10320
agcggcagga agtagttcat ggtggccgcg gtctggcccg tgaggcgcgc gcagtcgtgg 10380
atgctctaga catacgggca aaaacgaaag cggtcagcgg ctcgactccg tggcctggag 10440
gctaagcgaa cgggttgggc tgcgcgtgta ccccggttcg aatctcgaat caggctggag 10500
ccgcagctaa cgtggtactg gcactcccgt ctcgacccaa gcctgctaac gaaacctcca 10560
ggatacggag gcgggtcgtt ttttggcctt ggtcgctggt catgaaaaac tagtaagcgc 10620
ggaaagcgac cgcccgcgat ggctcgctgc cgtagtctgg agaaagaatc gccagggttg 10680
cgttgcggtg tgccccggtt cgagcctcag cgctcggcgc cggccggatt ccgcggctaa 10740
cgtgggcgtg gctgccccgt cgtttccaag accccttagc cagccgactt ctccagttac 10800
ggagcgagcc cctctttttc ttgtgttttt gccagatgca tcccgtactg cggcagatgc 10860
gcccccaccc tccacctcaa ccgcccctac cgccgcagca gcagcaacag ccggcgcttc 10920
tgcccccgcc ccagcagcag ccagccacta ccgcggcggc cgccgtgagc ggagccggcg 10980
ttcagtatga cctggccttg gaagagggcg aggggctggc gcggctgggg gcgtcgtcgc 11040
cggagcggca cccgcgcgtg cagatgaaaa gggacgctcg cgaggcctac gtgcccaagc 11100
agaacctgtt cagagacagg agcggcgagg agcccgagga gatgcgcgcc tcccgcttcc 11160
acgcggggcg ggagctgcgg cgcggcctgg accgaaagcg ggtgctgagg gacgaggatt 11220
tcgaggcgga cgagctgacg gggatcagcc ccgcgcgcgc gcacgtggcc gcggccaacc 11280
tggtcacggc gtacgagcag accgtgaagg aggagagcaa cttccaaaaa tccttcaaca 11340
accacgtgcg cacgctgatc gcgcgcgagg aggtgaccct gggcctgatg cacctgtggg 11400
acctgctgga ggccatcgtg cagaacccca cgagcaagcc gctgacggcg cagctgtttc 11460
tggtggtgca gcacagtcgg gacaacgaga cgttcaggga ggcgctgctg aatatcaccg 11520
agcccgaggg ccgctggctc ctggacctgg tgaacattct gcagagcatc gtggtgcagg 11580
agcgcgggct gccgctgtcc gagaagctgg cggctatcaa cttctcggtg ctgagcctgg 11640
gcaagtacta cgctaggaag atctacaaga ccccgtacgt gcccatagac aaggaggtga 11700
agatcgacgg gttttacatg cgcatgaccc tgaaagtgct gaccctgagc gacgatctgg 11760
gggtgtaccg caacgacagg atgcaccgcg cggtgagcgc cagccgccgg cgcgagctga 11820
gcgaccagga gctgatgcac agcctgcagc gggccctgac cggggccggg accgaggggg 11880
agagctactt tgacatgggc gcggacctgc gctggcagcc cagccgccgg gccttggaag 11940
ctgccggcgg ttccccctac gtggaggagg tggacgatga ggaggaggag ggcgagtacc 12000
tggaagactg atggcgcgac cgtatttttg ctagatgcag caacagccac cgcctcctga 12060
tcccgcgatg cgggcggcgc tgcagagcca gccgtccggc attaactcct cggacgattg 12120
gacccaggcc atgcaacgca tcatggcgct gacgacccgc aatcccgaag cctttagaca 12180
gcagcctcag gccaaccggc tctcggccat cctggaggcc gtggtgccct cgcgctcgaa 12240
ccccacgcac gagaaggtgc tggccatcgt gaacgcgctg gtggagaaca aggccatccg 12300
cggcgacgag gccgggctgg tgtacaacgc gctgctggag cgcgtggccc gctacaacag 12360
caccaacgtg cagacgaacc tggaccgcat ggtgaccgac gtgcgcgagg cggtgtcgca 12420
gcgcgagcgg ttccaccgcg agtcgaacct gggctccatg gtggcgctga acgccttcct 12480
gagcacgcag cccgccaacg tgccccgggg ccaggaggac tacaccaact tcatcagcgc 12540
gctgcggctg atggtggccg aggtgcccca gagcgaggtg taccagtcgg ggccggacta 12600
cttcttccag accagtcgcc agggcttgca gaccgtgaac ctgagccagg ctttcaagaa 12660
cttgcaggga ctgtggggcg tgcaggcccc ggtcggggac cgcgcgacgg tgtcgagcct 12720
gctgacgccg aactcgcgcc tgctgctgct gctggtggcg cccttcacgg acagcggcag 12780
cgtgagccgc gactcgtacc tgggctacct gcttaacctg taccgcgagg ccatcgggca 12840
ggcgcacgtg gacgagcaga cctaccagga gatcacccac gtgagccgcg cgctgggcca 12900
ggaggacccg ggcaacctgg aggccaccct gaacttcctg ctgaccaacc ggtcgcagaa 12960
gatcccgccc cagtacgcgc tgagcaccga ggaggagcgc atcctgcgct acgtgcagca 13020
gagcgtgggg ctgttcctga tgcaggaggg ggccacgccc agcgccgcgc tcgacatgac 13080
cgcgcgcaac atggagccca gcatgtacgc tcgcaaccgc ccgttcatca ataagctgat 13140
ggactacttg catcgggcgg ccgccatgaa ctcggactac tttaccaacg ccatcttgaa 13200
cccgcactgg ctcccgccgc ccgggttcta cacgggcgag tacgacatgc ccgaccccaa 13260
cgacgggttc ctgtgggacg acgtggacag cagcgtgttc tcgccgcgcc ccgccaccac 13320
cgtgtggaag aaagagggcg gggaccggcg gccgtcctcg gcgctgtccg gtcgcgcggg 13380
tgctgccgcg gcggtgcctg aggccgccag ccccttcccg agcctgccct tttcgctgaa 13440
cagcgtgcgc agcagcgagc tgggtcggct gacgcggccg cgcctgctgg gcgaggagga 13500
gtacctgaac gactccttgt tgaggcccga gcgcgagaag aacttcccca ataacgggat 13560
agagagcctg gtggacaaga tgagccgctg gaagacgtac gcgcacgagc acagggacga 13620
gccccgagct agcagcagcg caggcacccg tagacgccag cgacacgaca ggcagcgggg 13680
tctggtgtgg gacgatgagg attccgccga cgacagcagc gtgttggact tgggtgggag 13740
tggtggtggt aacccgttcg ctcacttgcg cccccgtatc gggcgcctga tgtaagaatc 13800
tgaaaaaata aaaaacggta ctcaccaagg ccatggcgac cagcgtgcgt tcttctctgt 13860
tgtttgtagt agtatgatga ggcgcgtgta cccggagggt cctcctccct cgtacgagag 13920
cgtgatgcag caggcggtgg cggcggcgat gcagcccccg ctggaggcgc cttacgtgcc 13980
cccgcggtac ctggcgccta cggaggggcg gaacagcatt cgttactcgg agctggcacc 14040
cttgtacgat accacccggt tgtacctggt ggacaacaag tcggcggaca tcgcctcgct 14100
gaactaccag aacgaccaca gcaacttcct gaccaccgtg gtgcagaaca acgatttcac 14160
ccccacggag gccagcaccc agaccatcaa ctttgacgag cgctcgcggt ggggcggcca 14220
gctgaaaacc atcatgcaca ccaacatgcc caacgtgaac gagttcatgt acagcaacaa 14280
gttcaaggcg cgggtgatgg tctcgcgcaa gacccccaat ggggtcgcgg tggatgagaa 14340
ttatgatggt agtcaggacg agctgactta cgagtgggtg gagtttgagc tgcccgaggg 14400
caacttctcg gtgaccatga ccatcgatct gatgaacaac gccatcatcg acaactactt 14460
ggcggtgggg cgtcagaacg gggtgctgga gagcgacatc ggcgtgaagt tcgacacgcg 14520
caacttccgg ctgggctggg accccgtgac cgagctggtg atgccgggcg tgtacaccaa 14580
cgaggccttc caccccgaca tcgtcctgct gcccggctgc ggcgtggact tcaccgagag 14640
ccgcctcagc aacctgctgg gcatccgcaa gcggcagccc ttccaggagg gcttccagat 14700
cctgtacgag gacctggagg ggggcaacat ccccgcgctc ttggatgtcg aagcctatga 14760
gaaaagcaag gaggaggccg ccgcagcggc gaccgcagcc gtggccaccg cctctaccga 14820
ggtgcggggc gataattttg ctagcgccgc ggcagtggcc gaggcggctg aaaccgaaag 14880
taagatagtc atccagccgg tggagaagga cagcaaggac aggagctaca acgtgctcgc 14940
ggacaagaaa aacaccgcct accgcagctg gtacctggcc tacaactacg gcgaccccga 15000
gaagggcgtg cgctcctgga cgctgctcac cacctcggac gtcacctgcg gcgtggagca 15060
agtctactgg tcgctgcccg acatgatgca agacccggtc accttccgct ccacgcgtca 15120
agttagcaac tacccggtgg tgggcgccga gctcctgccc gtctactcca agagcttctt 15180
caacgagcag gccgtctact cgcagcagct gcgcgccttc acctcgctca cgcacgtctt 15240
caaccgcttc cccgagaacc agatcctcgt ccgcccgccc gcgcccacca ttaccaccgt 15300
cagtgaaaac gttcctgctc tcacagatca cgggaccctg ccgctgcgca gcagtatccg 15360
gggagtccag cgcgtgaccg tcactgacgc cagacgccgc acctgcccct acgtctacaa 15420
ggccctgggc gtagtcgcgc cgcgcgtcct ctcgagccgc accttctaaa aaatgtccat 15480
tctcatctcg cccagtaata acaccggttg gggcctgcgc gcgcccagca agatgtacgg 15540
aggcgctcgc caacgctcca cgcaacaccc cgtgcgcgtg cgcgggcact tccgcgctcc 15600
ctggggcgcc ctcaagggcc gcgtgcgctc gcgcaccacc gtcgacgacg tgatcgacca 15660
ggtggtggcc gacgcgcgca actacacgcc cgccgccgcg cccgcctcca ccgtggacgc 15720
cgtcatcgac agcgtggtgg ccgatgcgcg ccggtacgcc cgcgccaaga gccggcggcg 15780
gcgcatcgcc cggcggcacc ggagcacccc cgccatgcgc gcggcgcgag ccttgctgcg 15840
cagggccagg cgcacgggac gcagggccat gctcagggcg gccagacgcg cggcctccgg 15900
cagcagcagc gccggcagga cccgcagacg cgcggccacg gcggcggcgg cggccatcgc 15960
cagcatgtcc cgcccgcggc gcggcaacgt gtactgggtg cgcgacgccg ccaccggtgt 16020
gcgcgtgccc gtgcgcaccc gcccccctcg cacttgaaga tgctgacttc gcgatgttga 16080
tgtgtcccag cggcgaggag gatgtccaag cgcaaataca aggaagagat gctccaggtc 16140
atcgcgcctg agatctacgg ccccgcggtg aaggaggaaa gaaagccccg caaactgaag 16200
cgggtcaaaa aggacaaaaa ggaggaggaa gatgtggacg gactggtgga gtttgtgcgc 16260
gagttcgccc cccggcggcg cgtgcagtgg cgcgggcgga aagtgaaacc ggtgctgcgg 16320
cccggcacca cggtggtctt cacgcccggc gagcgttccg gctccgcctc caagcgctcc 16380
tacgacgagg tgtacgggga cgaggacatc ctcgagcagg cggtcgagcg tctgggcgag 16440
tttgcttacg gcaagcgcag ccgccccgcg cccttgaaag aggaggcggt gtccatcccg 16500
ctggaccacg gcaaccccac gccgagcctg aagccggtga ccctgcagca ggtgctgccg 16560
agcgcggcgc cgcgccgggg cttcaagcgc gagggcggcg aggatctgta cccgaccatg 16620
cagctgatgg tgcccaagcg ccagaagctg gaggacgtgc tggagcacat gaaggtggac 16680
cccgaggtgc agcccgaggt caaggtgcgg cccatcaagc aggtggcccc gggcctgggc 16740
gtgcagaccg tggacatcaa gatccccacg gagcccatgg aaacgcagac cgagcccgtg 16800
aagcccagca ccagcaccat ggaggtgcag acggatccct ggatgccggc gccggcttcc 16860
accactcgcc gaagacgcaa gtacggcgcg gccagcctgc tgatgcccaa ctacgcgctg 16920
catccttcca tcatccccac gccgggctac cgcggcacgc gcttctaccg cggctacacc 16980
agcagccgcc gcaagaccac cacccgccgc cgccgtcgtc gcacccgccg cagcagcacc 17040
gcgacttccg ccgccgccct ggtgcggaga gtgtaccgca gcgggcgcga gcctctgacc 17100
ctgccgcgcg cgcgctacca cccgagcatc gccatttaac tctgccgtcg cctcctactt 17160
gcagatatgg ccctcacatg ccgcctccgc gtccccatta cgggctaccg aggaagaaag 17220
ccgcgccgta gaaggctgac ggggaacggg ctgcgtcgcc atcaccaccg gcggcggcgc 17280
gccatcagca agcggttggg gggaggcttc ctgcccgcgc tgatccccat catcgccgcg 17340
gcgatcgggg cgatccccgg catagcttcc gtggcggtgc aggcctctca gcgccactga 17400
gacacagctt ggaaaatttg taataaaaaa atggactgac gctcctggtc ctgtgatgtg 17460
tgtttttaga tggaagacat caatttttcg tccctggcac cgcgacacgg cacgcggccg 17520
tttatgggca cctggagcga catcggcaac agccaactga acgggggcgc cttcaattgg 17580
agcagtctct ggagcgggct taagaatttc gggtccacgc tcaaaaccta tggcaacaag 17640
gcgtggaaca gcagcacagg gcaggcgctg agggaaaagc tgaaagagca gaacttccag 17700
cagaaggtgg tcgatggcct ggcctcgggc atcaacgggg tggtggacct ggccaaccag 17760
gccgtgcaga aacagatcaa cagccgcctg gacgcggtcc cgcccgcggg gtccgtggag 17820
atgccccagg tggaggagga gctgcctccc ctggacaagc gcggcgacaa gcgaccgcgt 17880
cccgacgcgg aggagacgct gctgacgcac acggacgagc cgcccccgta cgaggaggcg 17940
gtgaaactgg gtctgcccac cacgcggccc gtggcgcctc tggccaccgg ggtgctgaaa 18000
cccagcagca gcagccagcc cgcgaccctg gacttgcctc cgcctgcttc ccgcccctcc 18060
acagtggcta agcccctgcc gccggtggcc gtcgcgtcgc gcgccccccg aggccgcccc 18120
caggcgaact ggcagagcac tctgaacagc atcgtgggtc tgggagtgca gagtgtgaag 18180
cgccgccgct gctattaaaa gacactgtag cgcttaactt gcttgtctgt gtgtatatgt 18240
atgtccgccg accagaagga ggaagaggcg cgtcgccgag ttgcaagatg gccaccccat 18300
cgatgctgcc ccagtgggcg tacatgcaca tcgccggaca ggacgcttcg gagtacctga 18360
gtccgggtct ggtgcagttc gcccgcgcca cagacaccta cttcagtctg gggaacaagt 18420
ttaggaaccc cacggtggcg cccacgcacg atgtgaccac cgaccgcagc cagcggctga 18480
cgctgcgctt cgtgcccgtg gaccgcgagg acaacaccta ctcgtacaaa gtgcgctaca 18540
cgctggccgt gggcgacaac cgcgtgctgg acatggccag cacctacttt gacatccgcg 18600
gcgtgctgga tcgggggccc agcttcaaac cctactccgg caccgcctac aacagcctgg 18660
ctcccaaggg agcgcccaac acttgccagt ggacatataa agctggtgat actgatacag 18720
aaaaaaccta tacatatgga aatgcacctg tgcaaggcat tagcattaca aaggatggta 18780
ttcaacttgg aactgacagc gatggtcagg caatctatgc agacgaaact tatcaaccag 18840
agcctcaagt gggtgatgct gaatggcatg acatcactgg tactgatgaa aaatatggag 18900
gcagagctct taagcctgac accaaaatga agccttgcta tggttctttt gccaagccta 18960
ccaataaaga aggaggccag gcaaatgtga aaaccgaaac aggcggtacc aaagaatatg 19020
acattgacat ggcattcttc gataatcgaa gtgcagctgc cgccggccta gccccagaaa 19080
ttgttttgta tactgagaat gtggatctgg aaactccaga tacccatatt gtatacaagg 19140
caggtacaga tgacagtagc tcttctatca atttgggtca gcagtccatg cccaacagac 19200
ccaactacat tggcttcaga gacaacttta tcggtctgat gtactacaac agcactggca 19260
atatgggtgt actggctgga caggcctccc agctgaatgc tgtggtggac ttgcaggaca 19320
gaaacaccga actgtcctac cagctcttgc ttgactctct gggtgacaga accaggtatt 19380
tcagtatgtg gaatcaggcg gtggacagtt atgaccccga tgtgcgcatt attgaaaatc 19440
acggtgtgga ggatgaactt cctaactatt gcttccccct ggatgctgtg ggtagaactg 19500
atacttacca gggaattaag gccaatggtg ataatcaaac cacctggacc aaagatgata 19560
ctgttaatga tgctaatgaa ttgggcaagg gcaatccttt cgccatggag atcaacatcc 19620
aggccaacct gtggcggaac ttcctctacg cgaacgtggc gctgtacctg cccgactcct 19680
acaagtacac gccggccaac atcacgctgc ccaccaacac caacacctac gattacatga 19740
acggccgcgt ggtggcgccc tcgctggtgg acgcctacat caacatcggg gcgcgctggt 19800
cgctggaccc catggacaac gtcaacccct tcaaccacca ccgcaacgcg ggcctgcgat 19860
accgctccat gctcctgggc aacgggcgct acgtgccctt ccacatccag gtgccccaaa 19920
agtttttcgc catcaagagc ctcctgctcc tgcccgggtc ctacacctac gagtggaact 19980
tccgcaagga cgtcaacatg atcctgcaga gctccctcgg caacgacctg cgcacggacg 20040
gggcctccat cgccttcacc agcatcaacc tctacgccac cttcttcccc atggcgcaca 20100
acaccgcctc cacgctcgag gccatgctgc gcaacgacac caacgaccag tccttcaacg 20160
actacctctc ggcggccaac atgctctacc ccatcccggc caacgccacc aacgtgccca 20220
tctccatccc ctcgcgcaac tgggccgcct tccgcggctg gtccttcacg cgcctcaaga 20280
cccgcgagac gccctcgctc ggctccgggt tcgaccccta cttcgtctac tcgggctcca 20340
tcccctacct cgacggcacc ttctacctca accacacctt caagaaggtc tccatcacct 20400
tcgactcctc cgtcagctgg cccggcaacg accgcctcct gacgcccaac gagttcgaaa 20460
tcaagcgcac cgtcgacgga gaggggtaca acgtggccca gtgcaacatg accaaggact 20520
ggttcctggt ccagatgctg gcccactaca acatcggcta ccagggcttc tacgtgcccg 20580
agggctacaa ggaccgcatg tactccttct tccgcaactt ccagcccatg agccgccagg 20640
tcgtggacga ggtcaactac aaggactacc aggccgtcac cctggcctac cagcacaaca 20700
actcgggctt cgtcggctac ctcgcgccca ccatgcgcca gggccagccc taccccgcca 20760
actaccccta cccgctcatc ggcaagagcg ccgtcgccag cgtcacccag aaaaagttcc 20820
tctgcgaccg ggtcatgtgg cgcatcccct tctccagcaa cttcatgtcc atgggcgcgc 20880
tcaccgacct cggccagaac atgctctacg ccaactccgc ccacgcgcta gacatgaatt 20940
tcgaagtcga ccccatggat gagtccaccc ttctctatgt tgtcttcgaa gtcttcgacg 21000
tcgtccgagt gcaccagccc caccgcggcg tcatcgaggc cgtctacctg cgcacgccct 21060
tctcggccgg caacgccacc acctaagcct cttgcttctt gcaagatgac ggcctgcgcg 21120
ggctccggcg agcaggagct cagggccatc ctccgcgacc tgggctgcgg gccctgcttc 21180
ctgggcacct tcgacaagcg cttcccggga ttcatggccc cgcacaagct ggcctgcgcc 21240
atcgtcaaca cggccggccg cgagaccggg ggcgagcact ggctggcctt cgcctggaac 21300
ccgcgctccc acacctgcta cctcttcgac cccttcgggt tctcggacga gcgcctcaag 21360
cagatctacc agttcgagta cgagggcctg ctgcgtcgca gcgccctggc caccgaggac 21420
cgctgcgtca ccctggaaaa gtccacccag accgtgcagg gtccgcgctc ggccgcctgc 21480
gggctcttct gctgcatgtt cctgcacgcc ttcgtgcact ggcccgaccg ccccatggac 21540
aagaacccca ccatgaactt gctgacgggg gtgcccaacg gcatgctcca gtcgccccag 21600
gtggaaccca ccctgcgccg caaccaggag gcgctctacc gcttcctcaa cgcccactcc 21660
gcctactttc gctcccaccg cgcgcgcatc gagaaggcca ccgccttcga ccgcatgaat 21720
caagacatgt aatccggtgt gtgtatgtga atgctttatt catcataata aacagcacat 21780
gtttatgcca ccttctctga ggctctgact ttatttagaa atcgaagggg ttctgccggc 21840
tctcggcatg gcccgcgggc agggatacgt tgcggaactg gtacttgggc agccacttga 21900
actcggggat cagcagcttc ggcacgggga ggtcggggaa cgagtcgctc cacagcttgc 21960
gcgtgagttg cagggcgccc agcaggtcgg gcgcggagat cttgaaatcg cagttgggac 22020
ccgcgttctg cgcgcgagag ttacggtaca cggggttgca gcactggaac accatcaggg 22080
ccgggtgctt cacgctcgcc agcaccgtcg cgtcggtgat gccctccacg tccagatcct 22140
cggcgttggc catcccgaag ggggtcatct tgcaggtctg ccgccccatg ctgggcacgc 22200
agccgggctt gtggttgcaa tcgcagtgca gggggatcag catcatctgg gcctgctcgg 22260
agctcatgcc cgggtacatg gccttcatga aagcctccag ctggcggaag gcctgctgcg 22320
ccttgccgcc ctcggtgaag aagaccccgc aggacttgct agagaactgg ttggtggcgc 22380
agccagcgtc gtgcacgcag cagcgcgcgt cgttgttggc cagctgcacc acgctgcgcc 22440
cccagcggtt ctgggtgatc ttggcccggt cggggttctc cttcagcgcg cgctgcccgt 22500
tctcgctcgc cacatccatc tcgatcgtgt gctccttctg gatcatcacg gtcccgtgca 22560
ggcaccgcag cttgccctcg gcctcggtgc acccgtgcag ccacagcgcg cagccggtgc 22620
tctcccagtt cttgtgggcg atctgggagt gcgagtgcac gaagccctgc aggaagcggc 22680
ccatcatcgt ggtcagggtc ttgttgctgg tgaaggtcag cggaatgccg cggtgctcct 22740
cgttcacata caggtggcag atacggcggt acacctcgcc ctgctcgggc atcagctgga 22800
aggcggactt caggtcgctc tccacgcggt accggtccat cagcagcgtc atcacttcca 22860
tgcccttctc ccaggccgaa acgatcggca ggctcagggg gttcttcacc gttgtcatct 22920
tagtcgccgc cgccgaagtc agggggtcgt tctcgtccag ggtctcaaac actcgcttgc 22980
cgtccttctc ggtgatgcgc acggggggaa agctgaagcc cacggccgcc agctcctcct 23040
cggcctgcct ttcgtcctcg ctgtcctggc tgatgtcttg caaaggcaca tgcttggtct 23100
tgcggggttt ctttttgggc ggcagaggcg gcggcggaga cgtgctgggc gagcgcgagt 23160
tctcgctcac cacgactatt tcttctcctt ggccgtcgtc cgagaccacg cggcggtagg 23220
catgcctctt ctggggcaga ggcggaggcg acgggctctc gcggttcggc gggcggctgg 23280
cagagcccct tccgcgttcg ggggtgcgct cctggcggcg ctgctctgac tgacttcctc 23340
cgcggccggc cattgtgttc tcctagggag caagcatgga gactcagcca tcgtcgccaa 23400
catcgccatc tgcccccgcc gccgccgacg agaaccagca gcagcagaat gaaagcttaa 23460
ccgccccgcc gcccagcccc acctccgacg ccgcagcccc agacatgcaa gagatggagg 23520
aatccatcga gattgacctg ggctacgtga cgcccgcgga gcacgaggag gagctggcag 23580
cgcgcttttc agccccggaa gagaaccacc aagagcagcc agagcaggaa gcagagagcg 23640
agcagaacca ggctgggctc gagcatggcg actacctgag cggggcagag gacgtgctca 23700
tcaagcatct ggcccgccaa tgcatcatcg tcaaggacgc gctgctcgac cgcgccgagg 23760
tgcccctcag cgtggcggag ctcagccgcg cctacgagcg caacctcttc tcgccgcgcg 23820
tgccccccaa gcgccagccc aacggcacct gcgagcccaa cccgcgcctc aacttctacc 23880
cggtcttcgc ggtgcccgag gccctggcca cctaccacct ctttttcaag aaccaaagga 23940
tccccgtctc ctgccgcgcc aaccgcaccc gcgccgacgc cctgctcaac ctgggccccg 24000
gcgcccgcct acctgatatc gcctccttgg aagaggttcc caagatcttc gagggtctgg 24060
gcagcgacga gactcgggcc gcgaacgctc tgcaaggaag cggagaggag catgagcacc 24120
acagcgccct ggtggagttg gaaggcgaca acgcgcgcct ggcggtcctc aagcgcacgg 24180
tcgagctgac ccacttcgcc tacccggcgc tcaacctgcc ccccaaggtc atgagcgccg 24240
tcatggacca ggtgctcatc aagcgcgcct cgcccctctc ggaggaggag atgcaggacc 24300
ccgagagctc ggacgagggc aagcccgtgg tcagcgacga gcagctggcg cgctggctgg 24360
gagagcagtc aggcagagga ggaggagatg gaagactggg acagcactca ggcagaggag 24420
gagcgagtag caccccccag agcctggaag agcggcgcaa gctcatgatg gccgtggtcc 24480
tggtgaccgt ggagctggag tgtctgcgcc gcttcttcgc cgacgcggag accctgcgca 24540
aggtcgagga gaacctgcac tacctcttca gacacgggtt cgtgcgccag gcctgcaaga 24600
tctccaacgt ggagctgacc aacctggtct cctacatggg catcctgcac gagaaccgcc 24660
tggggcagaa cgtgctgcac accaccctgc gcggggaggc ccgccgcgac tacatccgcg 24720
actgcgtcta cctgtacctc tgccacacct ggcagacggg catgggcgtg tggcagcagt 24780
gcctggagga gcagaacctg aaagagctct gcaagctcct gcagaagaac ctcaaggccc 24840
tgtggaccgg gttcgacgag cgcaccaccg ccgcggacct ggccgacctc atcttccccg 24900
agcgcctgcg gctgacgctg cgcaacgggc tgcccgactt tatgagccaa agcatgttgc 24960
aaaactttcg ctctttcatc ctcgaacgct ccgggatcct gcccgccacc tgctccgcgc 25020
tgccctcgga cttcgtgccg ctgaccttcc gcgagtgccc cccgccgctc tggagccact 25080
gctacctgct gcgcctggcc aactacctgg cctaccactc ggacgtgatc gaggacgtca 25140
gcggcgaggg cctgctcgag tgccactgcc gctgcaacct ctgcacgccg caccgctccc 25200
tggcctgcaa cccccagctg ctgagcgaga cccagatcat cggcaccttc gagttgcaag 25260
gccccggcga gggcaagggg ggtctgaaac tcaccccggg gctgtggacc tcggcctact 25320
tgcgcaagtt cgtgcccgag gactaccatc ccttcgagat caggttctac gaggaccaat 25380
cccagccgcc caaggccgag ctgtcggcct gcgtcatcac ccagggggcc atcctggccc 25440
aattgcaagc catccagaaa tcccgccaag aatttctgct gaaaaagggc cacggggtct 25500
acttggaccc ccagaccgga gaggagctca accccagctt cccccaggat gccccgagga 25560
agcagcaaga agctgaaagt ggagctgccg ccgccgccgg aggatttgga ggaagactgg 25620
gacagcctgc aagacagtct ggaggaggaa gacgaggtgg aggaggcaga ggaagaagca 25680
gccgccgcca gaccgtcgtc ctcggcggag gaggagaaag caagcagcac ggataccatc 25740
tccgctccgg gtcggggtcg cggcggccgg gcccacagta gatgggacga gaccgggcgc 25800
ttcccgaacc ccaccaccca gaccggtaag aaggagcggc agggatacaa gtcctggcgg 25860
gggcacaaaa acgccatcgt ctcctgcttg caagcctgcg ggggcaacat ctccttcacc 25920
cggcgctacc tgctcttcca ccgcggggtg aacttccccc gcaacatctt gcattactac 25980
cgtcacctcc acagccccta ctactgtttc caagaagagg cagaaaccca gcagcagcag 26040
cagcagcaga aaaccagcgg cagcagctag aaaatccaca gcggcggcag gtggactgag 26100
gatcgcggcg aacgagccgg cgcagacccg ggagctgagg aaccggatct ttcccaccct 26160
ctatgccatc ttccagcaga gtcgggggca agagcaggaa ctgaaagtca agaaccgttc 26220
tctgcgctcg ctcacccgca gttgtctgta tcacaagagc gaagaccaac ttcagcgcac 26280
tctcgaggac gccgaggctc tcttcaacaa gtactgcgcg ctcactctta aagagtagcc 26340
cgcgcccgcc cacacacgga aaaaggcggg aattacgtca ccacctgcgc ccttcgcccg 26400
accatcatca tgagcaaaga gattcccacg ccttacatgt ggagctacca gccccagatg 26460
ggcctggccg ccggcgccgc ccaggactac tccacccgca tgaactggct cagtgccggg 26520
cccgcgatga tctcacgggt gaatgacatc cgcgcccacc gaaaccagat actcctagaa 26580
cagtcagcga tcaccgccac gccccgccat caccttaatc cgcgtaattg gcccgccgcc 26640
ctggtgtacc aggaaattcc ccagcccacg accgtactac ttccgcgaga cgcccaggcc 26700
gaagtccagc tgactaactc aggtgtccag ctggccggcg gcgccgccct gtgtcgtcac 26760
cgccccgctc agggtataaa gcggctggtg atccgaggca gaggcacaca gctcaacgac 26820
gaggtggtga gctcttcgct gggtctgcga cctgacggag tcttccaact cgccggatcg 26880
gggagatctt ccttcacgcc tcgtcaggcc gtcctgactt tggagagttc gtcctcgcag 26940
ccccgctcgg gtggcatcgg cactctccag ttcgtggagg agttcactcc ctcggtctac 27000
ttcaacccct tctccggctc ccccggccac tacccggacg agttcatccc gaacttcgac 27060
gccatcagcg agtcggtgga cggctacgat tgaatgtccc atggtggcgc ggctgaccta 27120
gctcggcttc gacacctgga ccactgccgc cgcttccgct gcttcgctcg ggatctcgcc 27180
gagtttgcct actttgagct gcccgaggag caccctcagg gcccggccca cggagtgcgg 27240
atcgtcgtcg aagggggtct cgactcccac ctgcttcgga tcttcagcca gcgtccgatc 27300
ctggccgagc gcgagcaagg acagaccctt ctgaccctgt actgcatctg caaccacccc 27360
ggcctgcatg aaagtctttg ttgtctgctg tgtactgagt ataataaaag ctgagatcag 27420
cgactactcc ggacttccgt gtgttcctgc tatcaaccag tccctgttct tcaccgggaa 27480
cgagaccgag ctccagctcc agtgtaagcc ccacaagaag tacctcacct ggctgttcca 27540
gggctctccg atcgccgttg tcaaccactg cgacaacgac ggagtcctgc tgagcggccc 27600
tgccaacctt actttttcca cccgcagaag caagctccag ctcttccaac ccttcctccc 27660
cgggacctat cagtgcgtct cgggaccctg ccatcacacc ttccacctga tcccgaatac 27720
cacagcgtcg ctccccgcta ctaacaacca aactacccac caacgccacc gtcgcgacct 27780
ttcctctggg tctaatacca ctaccggagg tgagctccga ggtcgaccaa cctctgggat 27840
ttactacggc ccctgggagg tggtagggtt aatagcgcta ggcctagttg cgggtgggct 27900
tttggctctc tgctacctat acctcccttg ctgttcgtac ttagtggtgc tgtgttgctg 27960
gtttaagaaa tggggaagat caccctagtg agctgcggtg tgctggtggc ggtggtgctt 28020
tcgattgtgg gactgggcgg cgcggctgta gtgaaggaga aggccgatcc ctgcttgcat 28080
ttcaatcccg acaaatgcca gctgagtttt cagcccgatg gcaatcggtg cgcggtgctg 28140
atcaagtgcg gatgggaatg cgagaacgtg agaatcgagt acaataacaa gactcggaac 28200
aatactctcg cgtccgtgtg gcagcccggg gaccccgagt ggtacaccgt ctctgtcccc 28260
ggtgctgacg gctccccgcg caccgtgaat aatactttca tttttgcgca catgtgcgac 28320
acggtcatgt ggatgagcaa gcagtacgat atgtggcccc ccacgaagga gaacatcgtg 28380
gtcttctcca tcgcttacag cgtgtgcacg gcgctaatca ccgctatcgt gtgcctgagc 28440
attcacatgc tcatcgctat tcgccccaga aataatgccg aaaaagaaaa acagccataa 28500
cacgtttttt cacacacctt tttcagacca tggcctctgt taaatttttg cttttatttg 28560
ccagtctcat tgccgtcatt catggaatga gtaatgagaa aattactatt tacactggca 28620
ctaatcacac attgaaaggt ccagaaaaag ccacagaagt ttcatggtat tgttatttta 28680
atgaatcaga tgtatctact gaactctgtg gaaacaataa caaaaaaaat gagagcatta 28740
ctctcatcaa gtttcaatgt ggatctgact taaccctaat taacatcact agagactatg 28800
taggtatgta ttatggaact acagcaggca tttcggacat ggaattttat caagtttctg 28860
tgtctgaacc caccacgcct agaatgacca caaccacaaa aactacacct gttaccacta 28920
tacagctcac taccaatggc tttcttgcca tgcttcaagt ggctgaaaat agcaccagca 28980
ttcaacccac cccacccagt gaggaaattc ccagatccat gattggcatt attgttgctg 29040
tagtggtgtg catgttgatc atcgccttgt gcatggtgta ctatgccttc tgctacagaa 29100
agcacagact gaacgacaag ctggaacact tactaagtgt tgaattttaa ttttttagaa 29160
ccatgaagat cctaggcctt ttagtttttt ctatcattac ctctgctcta tgcaattctg 29220
acaatgagga cgttactgtc gttgtcggat caaattatac actaaaaggt ccagcaaaag 29280
gtatgctttc gtggtattgt tggttcggaa ctgacgagca acagacagaa ctttgcaatg 29340
ctcaaaaagg caaaacctca aattctaaaa tctctaatta tcaatgcaat ggcactgact 29400
tagtattgct caatgtcacg aaagcatatg ctggcagtta cacctgccct ggagatgatg 29460
ccgacaatat gattttttac aaagtggaag tggttgatcc cactactcca ccgcccacca 29520
ccacaactac tcataccaca cacacagaac aaacaccaga ggcagcagaa gcagagttgg 29580
ccttccaggt tcacggagat tcctttgctg tcaatacccc tacacccgat cagcggtgtc 29640
cggggctgct cgtcagcggc attgtcggtg tgctttcggg attagcagtc ataatcatct 29700
gcatgttcat ttttgcttgc tgctatagaa ggctttaccg acaaaaatca gacccactgc 29760
tgaacctcta tgtttaattt tttccagagc catgaaggca gttagcgctc tagttttttg 29820
ttctttgatt ggcattgttt ttagtgctgg gtttttgaaa aatcttacca tttatgaagg 29880
tgagaatgcc actctagtgg gcatcagtgg tcaaaatgtc agctggctaa aataccatct 29940
agatgggtgg aaagacattt gcgattggaa tgtcactgtg tatacatgta atggagttaa 30000
cctcaccatt actaatgcca cccaagatca gaatggtagg tttaagggcc agagtttcac 30060
tagaaataat gggtatgaat cccataacat gtttatctat gacgtcactg tcatcagaaa 30120
tgagactgcc accaccacac agatgcccac tacacacagt tctaccacta ctaccatgca 30180
aaccacacag acaaccacta catcaactca gcatatgacc accactacag cagcaaagcc 30240
aagtagtgca gcgcctcagc cccaggcttt ggctttgaaa gctgcacaac ctagtacaac 30300
tactaggacc aatgagcaga ctactgaatt tttgtccact gtcgagagcc acaccacagc 30360
tacctccagt gccttctcta gcaccgccaa tctctcctcg ctttcctcta caccaatcag 30420
tcccgctact actcccaccc cagctcttct ccccactccc ctgaagcaaa ctgaggacag 30480
cggcatgcaa tggcagatca ccctgctcat tgtgatcggg ttggtcatcc tggccgtgtt 30540
gctctactac atcttctgcc gccgcattcc caacgcgcac cgcaaaccgg cctacaagcc 30600
catcgttatc gggcagccgg agccgcttca ggtggaaggg ggtctaagga atcttctctt 30660
ctcttttaca gtatggtgat tgaactatga ttcctagaca attcttgatc actattctta 30720
tctgcctcct ccaagtctgt gccaccctcg ctctggtggc caacgccagt ccagactgta 30780
ttgggccctt cgcctcctac gtgctctttg ccttcatcac ctgcatctgc tgctgtagca 30840
tagtctgcct gcttatcacc ttcttccagt tcattgactg gatctttgtg cgcatcgcct 30900
acctgcgcca ccacccccag taccgcgacc agcgagtggc gcggctgctc aggctcctct 30960
gataagcatg cgggctctgc tacttctcgc gcttctgctg ttagtgctcc cccgccccgt 31020
cgacccccgg tcccccactc agtcccccga agaggtccgc aaatgcaaat tccaagaacc 31080
ctggaaattc ctcaaatgct accgccaaaa atcagacatg cttcccagct ggatcatgat 31140
cattgggatc gtgaacattc tggcctgcac cctcatctcc tttgtgattt acccctgctt 31200
tgactttggt tggaactcgc cagaggcgct ctatctcccg cctgaacctg acacaccacc 31260
acagcaacct caggcacacg cactaccacc accacagcct aggccacaat acatgcccat 31320
attagactat gaggccgagc cacagcgacc catgctcccc gctattagtt acttcaatct 31380
aaccggcgga gatgactgac ccactggcca acaacaacgt caacgacctt ctcctggaca 31440
tggacggccg cgcctcggag cagcgactcg cccaacttcg cattcgccag cagcaggaga 31500
gagccgtcaa ggagctgcag gacggcatag ccatccacca gtgcaagaaa ggcatcttct 31560
gcctggtgaa acaggccaag atctcctacg aggtcacccc gaccgaccat cgcctctcct 31620
acgagctcct gcagcagcgc cagaagttca cctgcctggt cggagtcaac cccatcgtca 31680
tcacccagca gtcgggcgat accaaggggt gcatccactg ctcctgcgac tcccccgact 31740
gcgtccacac tctgatcaag accctctgcg gcctccgcga cctcctcccc atgaactaat 31800
caccccctta tccagtgaaa taaatatcat attgatgatg atttaaataa aaaataatca 31860
tttgatttga aataaagata caatcatatt gatgatttga gttttaaaaa ataaagaatc 31920
acttacttga aatctgatac caggtctctg tccatgtttt ctgccaacac cacctcactc 31980
ccctcttccc agctctggta ctgcagaccc cggcgggctg caaacttcct ccacacgctg 32040
aaggggatgt caaattcctc ctgtccctca atcttcattt tatcttctat cagatgtcca 32100
aaaagcgcgt ccgggtggat gatgacttcg accccgtcta cccctacgat gcagacaacg 32160
caccgaccgt gcccttcatc aaccccccct tcgtctcttc agatggattc caagagaagc 32220
ccctgggggt gctgtccctg cgactggctg accccgtcac caccaagaac ggggaaatca 32280
ccctcaagct gggagagggg gtggacctcg actcctcggg aaaactcatc tccaacacgg 32340
ccaccaaggc cgccgcccct ctcagttttt ccaacaacac catttccctt aacatggata 32400
cccctcttta taccaaagat ggaaaattat ccttacaagt ttctccaccg ttaaacatat 32460
taaaatcaac cattctgaac acattagctg tagcttatgg atcaggttta ggactgagtg 32520
gtggcactgc tcttgcagta cagttggcct ctccactcac ttttgatgaa aaaggaaata 32580
ttaaaattaa cctagccagt ggtccattaa cagttgatgc aagtcgactt agtatcaact 32640
gcaaaagagg ggtcactgtc actacctcag gagatgcaat tgaaagcaac ataagctggc 32700
ctaaaggtat aagatttgaa ggtaatggca tagctgcaaa cattggcaga ggattggaat 32760
ttggaaccac tagtacagag actgatgtca cagatgcata cccaattcaa gttaaattgg 32820
gtactggcct tacctttgac agtacaggcg ccattgttgc ttggaacaaa gaggatgata 32880
aacttacatt atggaccaca gccgacccct cgccaaattg caaaatatac tctgaaaaag 32940
atgccaaact cacactttgc ttgacaaagt gtggaagtca aattctgggt actgtgactg 33000
tattggcagt gaataatgga agtctcaacc caatcacaaa cacagtaagc actgcactcg 33060
tctccctcaa gtttgatgca agtggagttt tgctaagcag ctccacatta gacaaagaat 33120
attggaactt cagaaaggga gatgttacac ctgctgagcc ctatactaat gctataggtt 33180
ttatgcctaa cataaaggcc tatcctaaaa acacatctgc agcttcaaaa agccatattg 33240
tcagtcaagt ttatctcaat ggggatgagg ccaaaccact gatgctgatt attactttta 33300
atgaaactga ggatgcaact tgcacctaca gtatcacttt tcaatggaaa tgggatagta 33360
ctaagtacac aggtgaaaca cttgctacca gctccttcac cttctcctac atcgcccaag 33420
aatgaacact gtatcccacc ctgcatgcca acccttccca ccccactctg tctatggaaa 33480
aaactctgaa gcacaaaata aaataaagtt caagtgtttt attgattcaa cagttttaca 33540
ggattcgagc agttattttt cctccaccct cccaggacat ggaatacacc accctctccc 33600
cccgcacagc cttgaacatc tgaatgccat tggtgatgga catgcttttg gtctccacgt 33660
tccacacagt ttcagagcga gccagtctcg ggtcggtcag ggagatgaaa ccctccgggc 33720
actcccgcat ctgcacctca cagctcaaca gctgaggatt gtcctcggtg gtcgggatca 33780
cggttatctg gaagaagcag aagagcggcg gtgggaatca tagtccgcga acgggatcgg 33840
ccggtggtgt cgcatcaggc cccgcagcag tcgctgccgc cgccgctccg tcaagctgct 33900
gctcaggggg tccgggtcca gggactccct cagcatgatg cccacggccc tcagcatcag 33960
tcgtctggtg cggcgggcgc agcagcgcat gcggatctcg ctcaggtcgc tgcagtacgt 34020
gcaacacagg accaccaggt tgttcaacag tccatagttc aacacgctcc agccgaaact 34080
catcgcggga aggatgctac ccacgtggcc gtcgtaccag atcctcaggt aaatcaagtg 34140
gcgctccctc cagaacacgc tgcccacgta catgatctcc ttgggcatgt ggcggttcac 34200
cacctcccgg taccacatca ccctctggtt gaacatgcag ccccggatga tcctgcggaa 34260
ccacagggcc agcaccgccc cgcccgccat gcagcgaaga gaccccgggt cccggcaatg 34320
gcaatggagg acccaccgct cgtacccgtg gatcatctgg gagctgaaca agtctatgtt 34380
ggcacagcac aggcatatgc tcatgcatct cttcagcact ctcagctcct cgggggtcaa 34440
aaccatatcc cagggcacgg ggaactcttg caggacagcg aaccccgcag aacagggcaa 34500
tcctcgcaca taacttacat tgtgcatgga cagggtatcg caatcaggca gcaccgggtg 34560
atcctccacc agagaagcgc gggtctcggt ctcctcacag cgtggtaagg gggccggccg 34620
atacgggtga tggcgggacg cggctgatcg tgttcgcgac cgtgtcatga tgcagttgct 34680
ttcggacatt ttcgtacttg ctgtagcaga acctggtccg ggcgctgcac accgatcgcc 34740
ggcggcggtc ccggcgcttg gaacgctcgg tgttgaaatt gtaaaacagc cactctctca 34800
gaccgtgcag cagatctagg gcctcaggag tgatgaagat cccatcatgc ctgatagctc 34860
tgatcacatc gaccaccgtg gaatgggcca gacccagcca gatgatgcaa ttttgttggg 34920
tttcggtgac ggcgggggag ggaagaacag gaagaaccat gattaacttt taatccaaac 34980
ggtctcggag cacttcaaaa tgaaggtcgc ggagatggca cctctcgccc ccgctgtgtt 35040
ggtggaaaat aacagccagg tcaaaggtga tacggttctc gagatgttcc acggtggctt 35100
ccagcaaagc ctccacgcgc acatccagaa acaagacaat agcgaaagcg ggagggttct 35160
ctaattcctc aatcatcatg ttacactcct gcaccatccc cagataattt tcatttttcc 35220
agccttgaat gattcgaact agttcctgag gtaaatccaa gccagccatg ataaagagct 35280
cgcgcagagc gccctccacc ggcattctta agcacaccct cataattcca agatattctg 35340
ctcctggttc acctgcagca gattgacaag cggaatatca aaatctctgc cgcgatccct 35400
aagctcctcc ctcagcaata actgtaagta ctctttcata tcctctccga aatttttagc 35460
cataggacca ccaggaataa gattagggca agccacagta cagataaacc gaagtcctcc 35520
ccagtgagca ttgccaaatg caagactgct ataagcatgc tggctagacc cggtgatatc 35580
ttccagataa ctggacagaa aatcacccag gcaattttta agaaaatcaa caaaagaaaa 35640
atcctccagg tgcacgttta gagcctcggg aacaacgatg aagtaaatgc aagcggtgcg 35700
ttccagcatg gttagttagc tgatctgtaa aaaacaaaaa ataaaacatt aaaccatgct 35760
agcctggcga acaggtgggt aaatcgttct ctccagcacc aggcaggcca cggggtctcc 35820
ggcgcgaccc tcgtaaaaat tgtcgctatg attgaaaacc atcacagaga gacgttcccg 35880
gtggccggcg tgaatgattc gacaagatga atacaccccc ggaacattgg cgtccgcgag 35940
tgaaaaaaag cgcccgagga agcaataagg cactacaatg ctcagtctca agtccagcaa 36000
agcgatgcca tgcggatgaa gcacaaaatc ctcaggtgcg tacaaaatgt aattactccc 36060
ctcctgcaca ggcagcgaag cccccgatcc ctccagatac acatacaaag cctcagcgtc 36120
catagcttac cgagcagcag cacacaacag gcgcaagagt cagagaaagg ctgagctcta 36180
acctgtccac ccgctctctg ctcaatatat agcccagatc tacactgacg taaaggccaa 36240
agtctaaaaa tacccgccaa ataatcacac acgcccagca cacgcccaga aaccggtgac 36300
acactcaaaa aaatacgcgc acttcctcaa acgcccaaac tgccgtcatt tccgggttcc 36360
cacgctacgt catcggaatt cgactttcaa attccgtcga ccgttaaaaa cgtcacccgc 36420
cccgccccta acggtcgccc gtctctcggc caatcacctt cctccctccc caaattcaaa 36480
cagctcattt gcatattaac gcgcaccaaa agtttgaggt atattattga tgatg 36535
<210> 5
<211> 32020
<212> DNA
<213> 黑猩猩Pan 5 (CV23)基因组
<400> 5
catcatcaat aatatacctc aaacttttgg tgcgcgttaa tatgcaaatg aggtatttga 60
atttggggat gcggggcggt gattggctgc gggagcggcg accgttaggg gcggggcggg 120
tgacgttttg atgacgtggc cgtgaggcgg agccggtttg caagttctcg tgggaaaagt 180
gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 240
ggaaatgagg tgtttctggg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 300
aatgaggaag tgaaaatctg agtaattccg cgtttatggc agggaggagt atttgccgag 360
ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtatttt tcacctaaat 420
ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggt gtcagctgat cgccagggta 480
tttaaacctg cgctctctag tcaagaggcc actcttgagt gccagcgagt agagttttct 540
cctccgcgcc gcgagtcaga tctacacttt gaaagatgag gcacctgaga gacctgcccg 600
gtaatgtttt cctggctact gggaacgaga ttctggaact ggtggtggac gccatgatgg 660
gtgacgaccc tccggagccc cctaccccat ttgaagcgcc ttcgctgtac gatttgtatg 720
atctggaggt ggatgtgccc gagaacgacc ccaacgagga ggcggtgaat gatttgttta 780
gcgatgccgc gctgctggct gccgagcagg ctaatacgga ctctggctca gacagcgatt 840
cctctctcca taccccgaga cccggcagag gtgagaaaaa gatccccgag cttaaagggg 900
aagagctcga cctgcgctgc tatgaggaat gcttgcctcc gagcgatgat gaggaggacg 960
aggaggcgat tcgagctgca gcgaaccagg gagtgaaaac agcgagcgag ggctttagcc 1020
tggactgtcc tactctgccc ggacacggct gtaagtcttg tgaatttcat cgcatgaata 1080
ctggagataa gaatgtgatg tgtgccctgt gctatatgag agcttacaac cattgtgttt 1140
acagtaagtg tgattaactt tagctgggga ggcagagggt gactgggtgc tgactggttt 1200
atttatgtat atgtttttta tgtgtaggtc ccgtctctga cgtagatgag acccccacta 1260
cagagtgcat ttcatcaccc ccagaaattg gcgaggaacc gcccgaagat attattcata 1320
gaccagttgc agtgagagtc accgggcgta gagcagctgt ggagagtttg gatgacttgc 1380
tacagggtgg ggatgaacct ttggacttgt gtacccggaa acgccccagg cactaagtgc 1440
cacacatgtg tgtttactta aggtgatgtc agtatttata gggtgtggag tgcaataaaa 1500
tccgtgttga ctttaagtgc gtggtttatg actcaggggt ggggactgtg ggtatataag 1560
caggtgcaga cctgtgtggt cagttcagag caggactcat ggagatctgg acagtcttgg 1620
aagactttca ccagactaga cagctgctag agaactcatc ggagggagtc tcttacctgt 1680
ggagattctg cttcggtggg cctctagcta agctagtcta tagggccaag caggattata 1740
aggatcaatt tgaggatatt ttgagagagt gtcctggtat ttttgactct ctcaacttgg 1800
gccatcagtc tcactttaac cagagtattc tgagagccct tgacttttct actcctggca 1860
gaactaccgc cgcggtagcc ttttttgcct ttatccttga caaatggagt caagaaaccc 1920
atttcagcag ggattaccgt ctggactgct tagcagtagc tttgtggaga acatggaggt 1980
gccagcgcct gaatgcaatc tccggctact tgccagtaca gccggtagac acgctgagga 2040
tcctgagtct ccagtcaccc caggaacacc aacgccgcca gcagccgcag caggagcagc 2100
agcaagagga ggaccgagaa gagaacctga gagccggtct ggaccctccg gtggcggagg 2160
aggaggagta gctgacttgt ttcccgagct gcgccgggtg ctgactaggt cttccagtgg 2220
acgggagagg gggattaagc gggagaggca tgaggagact agccacagaa ctgaactgac 2280
tgtcagtctg atgagtcgca ggcgcccaga atcggtgtgg tggcatgagg tgcagtcgca 2340
ggggatagat gaggtctcag tgatgcatga gaaatattcc ctagaacaag tcaagacttg 2400
ttggttggag cccgaggatg attgggaggt agccatcagg aattatgcca agctggctct 2460
gaggccagac aagaagtaca agattaccaa actgattaat atcagaaatt cctgctacat 2520
ttcagggaat ggggccgagg tggagatcag tacccaggag agggtggcct tcagatgctg 2580
catgatgaat atgtacccgg gggtggtggg catggaggga gtcaccttta tgaacgcgag 2640
gttcaggggt gatgggtata atggggtggt ctttatggcc aacaccaagc tgacagtgca 2700
cggatgctcc ttctttggct tcaataacat gtgcattgag gcctggggca gtgtttcagt 2760
gaggggatgc agtttttcag ccaactggat gggggtcgtg ggcagaacca agagcatggt 2820
gtcagtgaag aaatgcctgt tcgagaggtg ccacctgggg gtgatgagcg agggcgaagc 2880
caaagtcaaa cactgcgcct ctaccgagac gggctgcttt gtactgatca agggcaatgc 2940
caaagtcaag cataatatga tctgtggggc ctcggatgag cgcggctacc agatgctgac 3000
ctgcgccggt gggaacagcc atatgctagc caccgtgcat gtggcctcgc acccccgcaa 3060
gacatggccc gagttcgagc acaacgtcat gacccgctgc aatgtgcacc tggggtcccg 3120
ccgaggcatg ttcatgccct accagtgcaa catgcaattt gtgaaggtgc tgctggagcc 3180
cgatgccatg tccagagtga gcctgacggg ggtgtttgac atgaatgtgg agctgtggaa 3240
aattctgaga tatgatgaat ccaagaccag gtgccgggcc tgcgaatgcg gaggcaagca 3300
cgccaggctt cagcccgtgt gtgtggaggt gacggaggac ctgcgacccg atcatttggt 3360
gttgtcctgc aacgggacgg agttcggctc cagcggggaa gaatctgact agagtgagta 3420
gtgtttggga ctgggtggga gcctgcatga tgggcagaat gactaaaatc tgtgtttttc 3480
tgcgcagcag catgagcgga agcgcctcct ttgagggagg ggtattcagc ccttatctga 3540
cggggcgtct cccctcctgg gcgggagtgc gtcagaatgt gatgggatcc acggtggacg 3600
gccggcccgt gcagcccgcg aactcttcaa ccctgaccta cgcgaccctg agctcctcgt 3660
ccgtggacgc agctgccgcc gcagctgctg cttccgccgc cagcgccgtg cgcggaatgg 3720
ccctgggcgc cggctactac agctctctgg tggccaactc gagttccacc aataatcccg 3780
ccagcctgaa cgaggagaag ctgctgctgc tgatggccca gctcgaggcc ctgacccagc 3840
gcctgggcga gctgacccag caggtggctc agctgcaggc ggagacgcgg gccgcggttg 3900
ccacggtgaa aaccaaataa aaaatgaatc aataaataaa cggagacggt tgttgatttt 3960
aacacagagt cttgaatctt tatttgattt ttcgcgcgcg gtaggccctg gaccaccggt 4020
ctcgatcatt gagcacccgg tggatctttt ccaggacccg gtagaggtgg gcttggatgt 4080
tgaggtacat gggcatgagc ccgtcccggg ggtggaggta gctccattgc agggcctcgt 4140
gctcgggggt ggtgttgtaa atcacccagt catagcaggg gcgcagggcg tggtgctgca 4200
cgatgtcctt gaggaggaga ctgatggcca cgggcagccc cttggtgtag gtgttgacga 4260
acctgttgag ctgggaggga tgcatgcggg gggagatgag atgcatcttg gcctggatct 4320
tgagattggc gatgttcccg cccagatccc gccgggggtt catgttgtgc aggaccacca 4380
gcacggtgta tccggtgcac ttggggaatt tgtcatgcaa cttggaaggg aaggcgtgaa 4440
agaatttgga gacgcccttg tgaccgccca ggttttccat gcactcatcc atgatgatgg 4500
cgatgggccc gtgggcggcg gcttgggcaa agacgtttcg ggggtcggac acatcgtagt 4560
tgtggtcctg ggtgagctcg tcataggcca ttttaatgaa tttggggcgg agggtgcccg 4620
actgggggac gaaggtgccc tcgatcccgg gggcgtagtt gccctcgcag atctgcatct 4680
cccaggcctt gagctcggag ggggggatca tgtccacctg cggggcgatg aaaaaaacgg 4740
tttccggggc gggggagatg agctgggccg aaagcaggtt ccggagcagc tgggacttgc 4800
cgcagccggt ggggccgtag atgaccccga tgaccggctg caggtggtag ttgagggaga 4860
gacagctgcc gtcctcgcgg aggagggggg ccacctcgtt catcatctcg cgcacatgca 4920
tgttctcgcg cacgagttcc gccaggaggc gctcgccccc aagcgagagg agctcttgca 4980
gcgaggcgaa gtttttcagc ggcttgagcc cgtcggccat gggcattttg gagagggtct 5040
gttgcaagag ttccagacgg tcccagagct cggtgatgtg ctctagggca tctcgatcca 5100
gcagacctcc tcgtttcgcg ggttggggcg actgcgggag tagggcacca ggcgatgggc 5160
gtccagcgag gccagggtcc ggtccttcca ggggcgcagg gtccgcgtca gcgtggtctc 5220
cgtcacggtg aaggggtgcg cgccgggctg ggcgcttgcg agggtgcgct tcaggctcat 5280
ccggctggtc gagaaccgct cccggtcggc gccctgcgcg tcggccaggt agcaattgag 5340
catgagttcg tagttgagcg cctcggccgc gtggcccttg gcgcggagct tacctttgga 5400
agtgtgtccg cagacgggac agaggaggga cttgagggcg tagagcttgg gggcgaggaa 5460
gacggactcg ggggcgtagg cgtccgcgcc gcagctggcg cagacggtct cgcactccac 5520
gagccaggtg aggtctggcc ggtcggggtc aaaaacgagg tttcctccgt gctttttgat 5580
gcgtttctta cctctggtct ccatgagctc gtgtccccgc tgggtgacaa agaggctgtc 5640
cgtgtccccg tagaccgact ttatgggccg gtcctcgagc ggggtgccgc ggtcctcgtc 5700
gtagaggaac cccgcccact ccgagacgaa ggcccgggtc caggccagca cgaaggaggc 5760
cacgtgggag gggtagcggt cgttgtccac cagcgggtcc accttctcca gggtatgcaa 5820
gcacatgtcc ccctcgtcca catccaggaa ggtgattggc ttgtaagtgt aggccacgtg 5880
accgggggtc ccggccgggg gggtataaaa gggggcgggc ccctgctcgt cctcactgtc 5940
ttccggatcg ctgtccagga gcgccagctg ttggggtagg tattccctct cgaaggcggg 6000
catgacctcg gcactcaggt tgtcagtttc tagaaacgag gaggatttga tattgacggt 6060
gccgttggag acgcctttca tgagcccctc gtccatctgg tcagaaaaga cgatcttttt 6120
gttgtcgagc ttggtggcga aggagccgta gagggcgttg gagagcagct tggcgatgga 6180
gcgcatggtc tggttctttt ccttgtcggc gcgctccttg gcggcgatgt tgagctgcac 6240
gtactcgcgc gccacgcact tccattcggg gaagacggtg gtgagcttgt cgggcacgat 6300
tctgacccgc cagccgcggt tgtgcagggt gatgaggtcc acgctggtgg ccacctcgcc 6360
gcgcaggggc tcgttggtcc agcagaggcg cccgcccttg cgcgagcaga aggggggcag 6420
cgggtccagc atgagctcgt cgggggggtc ggcgtccacg gtgaagatgc cgggcaggag 6480
ctcggggtcg aagtagctga tgcaggtgcc cagatcgtcc agcgccgctt gccagtcgcg 6540
cacggccagc gcgcgctcgt aggggctgag gggcgtgccc cagggcatgg ggtgcgtgag 6600
cgcggaggcg tacatgccgc agatgtcgta gacgtagagg ggctcctcga ggacgccgat 6660
gtaggtgggg tagcagcgcc ccccgcggat gctggcgcgc acgtagtcgt acagctcgtg 6720
cgagggcgcg aggagcccgg tgccgaggtt ggagcgctgc ggcttttcgg cgcggtagac 6780
gatctggcgg aagatggcgt gggagttgga ggagatggtg ggcctctgga agatgttgaa 6840
gtgggcgtgg ggcagtccga ccgagtccct gatgaagtgg gcgtaggagt cctgcagctt 6900
ggcgacgagc tcggcggtga cgaggacgtc cagggcgcag tagtcgaggg tctcttggat 6960
gatgtcgtac ttgagctggc ccttctgctt ccacagctcg cggttgagaa ggaactcttc 7020
gcggtccttc cagtactctt cgagggggaa cccgtcctga tcggcacggt aagagcccac 7080
catgtagaac tggttgacgg ccttgtaggc gcagcagccc ttctccacgg ggagggcgta 7140
agcttgcgcg gccttgcgca gggaggtgtg ggtgagggcg aaggtgtcgc gcaccatgac 7200
cttgaggaac tggtgcttga agtcgaggtc gtcgcagccg ccctgctccc agagctggaa 7260
gtccgtgcgc ttcttgtagg cggggttggg caaagcgaaa gtaacatcgt tgaagaggat 7320
cttgcccgcg cggggcatga agttgcgagt gatgcggaaa ggctggggca cctcggcccg 7380
gttgttgatg acctgggcgg cgaggacgat ctcgtcgaag ccgttgatgt tgtgcccgac 7440
gatgtagagt tccacgaatc gcgggcggcc cttgacgtgg ggcagcttct tgagctcgtc 7500
gtaggtgagc tcggcggggt cgctgaggcc gtgctgctcg agggcccagt cggcgaggtg 7560
ggggttggcg ccgaggaagg aagtccagag atccacggcc agggcggtct gcaagcggtc 7620
ccggtactga cggaactgct ggcccacggc cattttttcg ggggtgacgc agtagaaggt 7680
gcgggggtcg ccgtgccagc ggtcccactt gagctggagg gcgaggtcgt gggcgagctc 7740
gacgagcggc gggtccccgg agagtttcat gaccagcatg aaggggacga gctgcttgcc 7800
gaaggacccc atccaggtgt aggtttccac gtcgtaggtg aggaagagcc tttcggtgcg 7860
aggatgcgag ccgatgggga agaactggat ctcctgccac cagttggagg aatggctgtt 7920
gatgtgatgg aagtagaaat gccgacggcg cgccgagcac tcgtgcttgt gtttatacaa 7980
gcgtccgcag tgctcgcaac gctgcacggg atgcacgtgc tgcacgagct gtacctgggt 8040
tcctttgacg aggaatttca gtgggcagtg gagcgctggc ggctgcatct ggtgctgtac 8100
tacgtcctgg ccatcggcgt ggccatcgtc tgcctcgatg gtggtcatgc tgacgaggcc 8160
gcgcgggagg caggtccaga cctcggctcg gacgggtcgg agagcgagga cgagggcgcg 8220
caggccggag ctgtccaggg tcctgagacg ctgcggagtc aggtcagtgg gcagcggcgg 8280
cgcgcggttg acttgcagga gcttttccag ggcgcgcggg aggtccagat ggtacttgat 8340
ctccacggcg ccgttggtgg cgacgtccac ggcttgcagg gtcccgtgcc cctggggcgc 8400
caccaccgtg ccccgtttct tcttgggtgc tggcggcggc ggctccatgc ttagaagcgg 8460
cggcgaggac gcgcgccggg cggcaggggc ggctcggggc ccggaggcag gggcggcagg 8520
ggcacgtcgg cgccgcgcgc gggcaggttc tggtactgcg cccggagaag actggcgtga 8580
gcgacgacgc gacggttgac gtcctggatc tgacgcctct gggtgaaggc cacgggaccc 8640
gtgagtttga acctgaaaga gagttcgaca gaatcaatct cggtatcgtt gacggcggcc 8700
tgccgcagga tctcttgcac gtcgcccgag ttgtcctggt aggcgatctc ggtcatgaac 8760
tgctcgatct cctcctcctg aaggtctccg cgaccggcgc gctcgacggt ggccgcgagg 8820
tcgttggaga tgcggcccat gagctgcgag aaggcgttca tgccggcctc gttccagacg 8880
cggctgtaga ccacggctcc gtcggggtcg cgcgcgcgca tgaccacctg ggcgaggttg 8940
agctcgacgt ggcgcgtgaa gaccgcgtag ttgcagaggc gctggtagag gtagttgagc 9000
gtggtggcga tgtgctcggt gacgaagaag tacatgatcc agcggcggag cggcatctcg 9060
ctgacgtcgc ccagggcttc caagcgctcc atggcctcgt agaagtccac ggcgaagttg 9120
aaaaactggg agttgcgcgc cgagacggtc aactcctcct ccagaagacg gatgagctcg 9180
gcgatggtgg cgcgcacctc gcgctcgaag gccccggggg gctcctcttc ttccatctcc 9240
tcctcctctt ccatctcctc cactaacatc tcttctactt cctcctcagg aggcggcggc 9300
gggggagggg ccctgcgtcg ccggcggcgc acgggcagac ggtcgatgaa gcgctcgatg 9360
gtctccccgc gccggcgacg catggtctcg gtgacggcgc gcccgtcctc gcggggccgc 9420
agcgtgaaga cgccgccgcg catctccagg tggccgccgg gggggtctcc gttgggcagg 9480
gagagggcgc tgacgatgca tcttatcaat tggcccgtag ggactccgcg caaggacctg 9540
agcgtctcga gatccacggg atccgaaaac cgctgaacga aggcttcgag ccagtcgcag 9600
tcgcaaggta ggctgagccc ggtttcttgt tcttcgggta tttggtcggg aggcgggcgg 9660
gcgatgctgc tggtgatgaa gttgaagtag gcggtcctga gacggcggat ggtggcgagg 9720
agcaccaggt ccttgggccc ggcttgctgg atgcgcagac ggtcggccat gccccaggcg 9780
tggtcctgac acctggcgag gtccttgtag tagtcctgca tgagccgctc cacgggcacc 9840
tcctcctcgc ccgcgcggcc gtgcatgcgc gtgagcccga acccgcgctg cggctggacg 9900
agcgccaggt cggcgacgac gcgctcggcg aggatggcct gctggatctg ggtgagggtg 9960
gtctggaagt cgtcgaagtc gacgaagcgg tggtaggctc cggtgttgat ggtgtaggag 10020
cagttggcca tgacggacca gttgacggtc tggtggccgg ggcgcacgag ctcgtggtac 10080
ttgaggcgcg agtaggcgcg cgtgtcgaag atgtagtcgt tgcaggtgcg cacgaggtac 10140
tggtatccga cgaggaagtg cggcggcggc tggcggtaga gcggccatcg ctcggtggcg 10200
ggggcgccgg gcgcgaggtc ctcgagcatg aggcggtggt agccgtagat gtacctggac 10260
atccaggtga tgccggcggc ggtggtggag gcgcgcggga actcgcggac gcggttccag 10320
atgttgcgca gcggcaggaa gtagttcatg gtggccgcgg tctggcccgt gaggcgcgcg 10380
cagtcgtgga tgctctagac atacgggcaa aaacgaaagc ggtcagcggc tcgactccgt 10440
ggcctggagg ctaagcgaac gggttgggct gcgcgtgtac cccggttcga gtccctgctc 10500
gaatcaggct ggagccgcag ctaacgtggt actggcactc ccgtctcgac ccaagcctgc 10560
taacgaaacc tccaggatac ggaggcgggt cgttttggcc attttcgtca ggccggaaat 10620
gaaactagta agcgcggaaa gcggccgtcc gcgatggctc gctgccgtag tctggagaaa 10680
gaatcgccag ggttgcgttg cggtgtgccc cggttcgagc ctcagcgctc ggcgccggcc 10740
ggattccgcg gctaacgtgg gcgtggctgc cccgtcgttt ccaagacccc ttagccagcc 10800
gacttctcca gttacggagc gagcccctct ttttcttgtg tttttgccag atgcatcccg 10860
tactgcggca gatgcgcccc caccctccac cacaaccgcc cctaccgcag cagcagcaac 10920
agccggcgct tctgcccccg ccccagcagc agcagccagc cactaccgcg gcggccgccg 10980
tgagcggagc cggcgttcag tatgacctgg ccttggaaga gggcgagggg ctggcgcggc 11040
tgggggcgtc gtcgccggag cggcacccgc gcgtgcagat gaaaagggac gctcgcgagg 11100
cctacgtgcc caagcagaac ctgttcagag acaggagcgg cgaggagccc gaggagatgc 11160
gcgcctcccg cttccacgcg gggcgggagc tgcggcgcgg cctggaccga aagcgggtgc 11220
tgagggacga ggatttcgag gcggacgagc tgacggggat cagccccgcg cgcgcgcacg 11280
tggccgcggc caacctggtc acggcgtacg agcagaccgt gaaggaggag agcaacttcc 11340
aaaaatcctt caacaaccac gtgcgcacgc tgatcgcgcg cgaggaggtg accctgggcc 11400
tgatgcacct gtgggacctg ctggaggcca tcgtgcagaa ccccacgagc aagccgctga 11460
cggcgcagct gtttctggtg gtgcagcaca gtcgggacaa cgagacgttc agggaggcgc 11520
tgctgaatat caccgagccc gagggccgct ggctcctgga cctggtgaac attctgcaga 11580
gcatcgtggt gcaggagcgc gggctgccgc tgtccgagaa gctggcggcc atcaacttct 11640
cggtgctgag cctgggcaag tactacgcta ggaagatcta caagaccccg tacgtgccca 11700
tagacaagga ggtgaagatc gacgggtttt acatgcgcat gaccctgaaa gtgctgaccc 11760
tgagcgacga tctgggggtg taccgcaacg acaggatgca ccgcgcggtg agcgccagcc 11820
gccggcgcga gctgagcgac caggagctga tgcacagcct gcagcgggcc ctgaccgggg 11880
ccgggaccga gggggagagc tactttgaca tgggcgcgga cctgcgctgg cagcctagcc 11940
gccgggcctt ggaagctgcc ggcggttccc cctacgtgga ggaggtggac gatgaggagg 12000
aggagggcga gtacctggaa gactgatggc gcgaccgtat ttttgctaga tgcagcaaca 12060
gccaccgccg cctcctgatc ccgcgatgcg ggcggcgctg cagagccagc cgtccggcat 12120
taactcctcg gacgattgga cccaggccat gcaacgcatc atggcgctga cgacccgcaa 12180
tcccgaagcc tttagacagc agcctcaggc caaccgactc tcggccatcc tggaggccgt 12240
ggtgccctcg cgctcgaacc ccacgcacga gaaggtgctg gccatcgtga acgcgctggt 12300
ggagaacaag gccatccgcg gcgacgaggc cgggctggtg tacaacgcgc tgctggagcg 12360
cgtggcccgc tacaacagca ccaacgtgca gacgaacctg gaccgcatgg tgaccgacgt 12420
gcgcgaggcg gtgtcgcagc gcgagcggtt ccaccgcgag tcgaacctgg gctccatggt 12480
ggcgctgaac gccttcctga gcacgcagcc cgccaacgtg ccccggggcc aggaggacta 12540
caccaacttc atcagcgcgc tgcggctgat ggtggccgag gtgccccaga gcgaggtgta 12600
ccagtcgggg ccggactact tcttccagac cagtcgccag ggcttgcaga ccgtgaacct 12660
gagccaggct ttcaagaact tgcagggact gtggggcgtg caggccccgg tcggggaccg 12720
cgcgacggtg tcgagcctgc tgacgccgaa ctcgcgcctg ctgctgctgc tggtggcgcc 12780
cttcacggac agcggcagcg tgagccgcga ctcgtacctg ggctacctgc ttaacctgta 12840
ccgcgaggcc atcgggcagg cgcacgtgga cgagcagacc taccaggaga tcacccacgt 12900
gagccgcgcg ctgggccagg aggacccggg caacctggag gccaccctga acttcctgct 12960
gaccaaccgg tcgcagaaga tcccgcccca gtacgcgctg agcaccgagg aggagcgcat 13020
cctgcgctac gtgcagcaga gcgtggggct gttcctgatg caggaggggg ccacgcccag 13080
cgccgcgctc gacatgaccg cgcgcaacat ggagcccagc atgtacgccc gcaaccgccc 13140
gttcatcaat aagctgatgg actacttgca tcgggcggcc gccatgaact cggactactt 13200
taccaacgcc atcttgaacc cgcactggct cccgccgccc gggttctaca cgggcgagta 13260
cgacatgccc gaccccaacg acgggttcct gtgggacgac gtggacagca gcgtgttctc 13320
gccgcgcccc accaccacca ccgtgtggaa gaaagagggc ggggaccggc ggccgtcctc 13380
ggcgctgtcc ggtcgcgcgg gtgctgccgc ggcggtgccc gaggccgcca gccccttccc 13440
gagcctgccc ttttcgctga acagcgtgcg cagcagcgag ctgggtcggc tgacgcggcc 13500
gcgcctgctg ggcgaggagg agtacctgaa cgactccttg cttcggcccg agcgcgagaa 13560
gaacttcccc aataacggga tagagagcct ggtggacaag atgagccgct ggaagacgta 13620
cgcgcacgag cacagggacg agccccgagc tagcagcagc accggcgcca cccgtagacg 13680
ccagcggcac gacaggcagc ggggtctggt gtgggacgat gaggattccg ccgacgacag 13740
cagcgtgttg gacttgggtg ggagtggtgg tggtaacccg ttcgctcacc tgcgcccccg 13800
tatcgggcgc ctgatgtaag aatctgaaaa aataaaagac ggtactcacc aaggccatgg 13860
cgaccagcgt gcgttcttct ctgttgtttg tagtagtatg atgaggcgcg tgtacccgga 13920
gggtcctcct ccctcgtacg agagcgtgat gcagcaggcg gtggcggcgg cgatgcagcc 13980
cccgctggag gcgccttacg tgcccccgcg gtacctggcg cctacggagg ggcggaacag 14040
cattcgttac tcggagctgg cacccttgta cgataccacc cggttgtacc tggtggacaa 14100
caagtcggcg gacatcgcct cgctgaacta ccagaacgac cacagcaact tcctgaccac 14160
cgtggtgcag aacaacgatt tcacccccac ggaggccagc acccagacca tcaactttga 14220
cgagcgctcg cggtggggcg gccagctgaa aaccatcatg cacaccaaca tgcccaacgt 14280
gaacgagttc atgtacagca acaagttcaa ggcgcgggtg atggtctcgc gcaagacccc 14340
caacggggtc acagtaacag atggtagtca ggacgagctg acctacgagt gggtggagtt 14400
tgagctgccc gagggcaact tctcggtgac catgaccatc gatctgatga acaacgccat 14460
catcgacaac tacttggcgg tggggcggca gaacggggtg ctggagagcg acatcggcgt 14520
gaagttcgac acgcgcaact tccggctggg ctgggacccc gtgaccgagc tggtgatgcc 14580
gggcgtgtac accaacgagg ccttccaccc cgacatcgtc ctgctgcccg gctgcggcgt 14640
ggacttcacc gagagccgcc tcagcaacct gctgggcatc cgcaagcggc agcccttcca 14700
ggagggcttc cagatcctgt acgaggacct ggaggggggc aacatccccg cgctgctgga 14760
cgtggacgcc tacgagaaaa gcaaggagga tagcgccgcc gcggcgaccg cagccgtggc 14820
caccgcctct accgaggtgc ggggcgataa ttttgctagc gccgcgacac tggcagcggc 14880
cgaggcggct gaaaccgaaa gtaagatagt gatccagccg gtggagaagg acagcaagga 14940
gaggagctac aacgtgctcg cggacaagaa aaacaccgcc taccgcagct ggtacctggc 15000
ctacaactac ggcgaccccg agaagggcgt gcgctcctgg acgctgctca ccacctcgga 15060
cgtcacctgc ggcgtggagc aagtctactg gtcgctgccc gacatgatgc aagacccggt 15120
caccttccgc tccacgcgtc aagttagcaa ctacccggtg gtgggcgccg agctcctgcc 15180
cgtctactcc aagagcttct tcaacgagca ggccgtctac tcgcagcagc tgcgcgcctt 15240
cacctcgctc acgcacgtct tcaaccgctt ccccgagaac cagatcctcg ttcgcccgcc 15300
cgcgcccacc attaccaccg tcagtgaaaa cgttcctgct ctcacagatc acgggaccct 15360
gccgctgcgc agcagtatcc ggggagtcca gcgcgtgacc gtcactgacg ccagacgccg 15420
cacctgcccc tacgtctaca aggccctggg cgtagtcgcg ccgcgcgtcc tctcgagccg 15480
caccttctaa aaaatgtcca ttctcatctc gcccagtaat aacaccggtt ggggcctgcg 15540
cgcgcccagc aagatgtacg gaggcgctcg ccaacgctcc acgcaacacc ccgtgcgcgt 15600
gcgcgggcac ttccgcgctc cctggggcgc cctcaagggc cgcgtgcgct cgcgcaccac 15660
cgtcgacgac gtgatcgacc aggtggtggc cgacgcgcgc aactacacgc ccgccgccgc 15720
gcccgtctcc accgtggacg ccgtcatcga cagcgtggtg gccgacgcgc gccggtacgc 15780
ccgcgccaag agccggcggc ggcgcatcgc ccggcggcac cggagcaccc ccgccatgcg 15840
cgcggcgcga gccttgctgc gcagggccag gcgcacggga cgcagggcca tgctcagggc 15900
ggccagacgc gcggcctccg gcagcagcag cgccggcagg acccgcagac gcgcggccac 15960
ggcggcggcg gcggccatcg ccagcatgtc ccgcccgcgg cgcggcaacg tgtactgggt 16020
gcgcgacgcc gccaccggtg tgcgcgtgcc cgtgcgcacc cgcccccctc gcacttgaag 16080
atgctgactt cgcgatgttg atgtgtccca gcggcgagga ggatgtccaa gcgcaaattc 16140
aaggaagaga tgctccaggt catcgcgcct gagatctacg gcccggcggc ggtgaaggag 16200
gaaagaaagc cccgcaaact gaagcgggtc aaaaaggaca aaaaggagga ggaagatgtg 16260
gacggactgg tggagtttgt gcgcgagttc gccccccggc ggcgcgtgca gtggcgcggg 16320
cggaaagtga aaccggtgct gcgacccggc accacggtgg tcttcacgcc cggcgagcgt 16380
tccggctccg cctccaagcg ctcctacgac gaggtgtacg gggacgagga catcctcgag 16440
caggcggccg aacgtctggg cgagtttgct tacggcaagc gcagccgccc cgcgcccttg 16500
aaagaggagg cggtgtccat cccgctggac cacggcaacc ccacgccgag cctgaagccg 16560
gtgaccctgc agcaggtgct gcctggtgcg gcgccgcgcc ggggcttcaa gcgcgagggc 16620
ggcgaggatc tgtacccgac catgcagctg atggtgccca agcgccagaa gctggaggac 16680
gtgctggagc acatgaaggt ggaccccgag gtgcagcccg aggtcaaggt gcggcccatc 16740
aagcaggtgg ccccgggcct gggcgtgcag accgtggaca tcaagatccc cacggagccc 16800
atggaaacgc agaccgagcc cgtgaagccc agcaccagca ccatggaggt gcagacggat 16860
ccctggatgc cggcaccggc ttccaccacc cgccgaagac gcaagtacgg cgcggccagc 16920
ctgctgatgc ccaactacgc gctgcatcct tccatcatcc ccacgccggg ctaccgcggc 16980
acgcgcttct accgcggcta caccagcagc cgccgccgca agaccaccac ccgccgccgc 17040
cgtcgtcgca cccgccgcag cagcaccgcg acttccgccg ccgccctggt gcggagagtg 17100
taccgcagcg ggcgcgagcc tctgaccctg ccgcgcgcgc gctaccaccc gagcatcgcc 17160
atttaactac cgcctcctac ttgcagatat ggccctcaca tgccgcctcc gcgtccccat 17220
tacgggctac cgaggaagaa agccgcgccg tagaaggctg acggggaacg ggctgcgtcg 17280
ccatcaccac cggcggcggc gcgccatcag caagcggttg gggggaggct tcctgcccgc 17340
gctgatgccc atcatcgccg cggcgatcgg ggcgatcccc ggcatagctt ccgtggcggt 17400
gcaggcctct cagcgccact gagacacagc ttggaaaatt tgtaataaaa aatggactga 17460
cgctcctggt cctgtgatgt gtgtttttag atggaagaca tcaatttttc gtccctggca 17520
ccgcgacacg gcacgcggcc gtttatgggc acctggagcg acatcggcaa cagccaactg 17580
aacgggggcg ccttcaattg gagcagtctc tggagcgggc ttaagaattt cgggtccacg 17640
ctcaaaacct atggcaacaa ggcgtggaac agcagcacag ggcaggcgct gagggaaaag 17700
ctgaaagagc agaacttcca gcagaaggtg gtcgatggcc tggcctcggg catcaacggg 17760
gtggtggacc tggccaacca ggccgtgcag aaacagatca acagccgcct ggacgcggtc 17820
ccgcccgcgg ggtccgtgga gatgccccag gtggaggagg agctgcctcc cctggacaag 17880
cgcggcgaca agcgaccgcg tcccgacgcg gaggagacgc tgctgacgca cacggacgag 17940
ccgcccccgt acgaggaggc ggtgaaactg ggtctgccca ccacgcggcc cgtggcgcct 18000
ctggccaccg gggtgctgaa acccagcagc agcagcagcc agcccgcgac cctggacttg 18060
cctccgcctg cttcccgccc ctccacagtg gctaagcccc tgccgccggt ggccgtcgcg 18120
tcgcgcgccc cccgaggccg cccccaggcg aactggcaga gcactctgaa cagcatcgtg 18180
ggtctgggag tgcagagtgt gaagcgccgc cgctgctatt aaaagacact gtagcgctta 18240
acttgcttgt ctgtgtgtat atgtatgtcc gccgaccaga aggaggagga agaggcgcgt 18300
cgccgagttg caagatggcc accccatcga tgctgcccca gtgggcgtac atgcacatcg 18360
ccggacagga cgcttcggag tacctgagtc cgggtctggt gcagttcgcc cgcgccacag 18420
acacctactt cagtctgggg aacaagttta ggaaccccac ggtggcgccc acgcacgatg 18480
tgaccaccga ccgcagccag cggctgacgc tgcgcttcgt gcccgtggac cgcgaggaca 18540
acacctactc gtacaaagtg cgctacacgc tggccgtggg cgacaaccgc gtgctggaca 18600
tggccagcac ctactttgac atccgcggcg tgctggatcg gggccctagc ttcaaaccct 18660
actccggcac cgcttacaac agcctggctc ccaagggagc gcccaacact tgccagtgga 18720
catataaagc tgatggtgat actggtacag aaaaaaccta tacatatgga aatgcgcctg 18780
tgcaaggcat tagtattaca aaagatggta ttcaacttgg aactgacact gatgatcagc 18840
ccatttatgc agataaaact tatcaaccag agcctcaagt gggtgatgct gaatggcatg 18900
acatcactgg tactgatgaa aaatatggag gcagagctct caagcctgac accaaaatga 18960
agccctgcta tggttctttt gccaagccta ccaataaaga aggaggtcag gcaaatgtga 19020
aaaccgaaac aggcggtacc aaagaatatg acattgacat ggcattcttc gataatcgaa 19080
gtgcagctgc ggctggcctg gccccagaaa ttgttttgta tactgagaat gtggatctgg 19140
aaactccaga tactcatatt gtatacaagg cgggcacaga tgacagcagc tcttctatca 19200
atttgggtca gcagtccatg cccaacagac ccaactacat tggctttaga gacaacttta 19260
tcgggctcat gtactacaac agcactggca acatgggcgt gctggctggt caggcctccc 19320
agctgaatgc tgtggtggac ttgcaggaca gaaacactga actgtcctac cagctcttgc 19380
ttgactctct gggcgacaga accaggtatt tcagtatgtg gaatcaggcg gtggacagct 19440
atgaccccga tgtgcgcatt attgaaaatc acggtgtgga ggatgaactc cctaactatt 19500
gcttccccct ggatgctgtg ggtagaactg atacttacca gggaattaag gccaatggtg 19560
ctgatcaaac cacctggacc aaagatgata ctgttaatga tgctaatgaa ttgggcaagg 19620
gcaatccttt cgccatggag atcaacatcc aggccaacct gtggcggaac ttcctctacg 19680
cgaacgtggc gctgtacctg cccgactcct acaagtacac gccggccaac atcacgctgc 19740
cgaccaacac caacacctac gattacatga acggccgcgt ggtggcgccc tcgctggtgg 19800
acgcctacat caacatcggg gcgcgctggt cgctggaccc catggacaac gtcaacccct 19860
tcaaccacca ccgcaacgcg ggcctgcgct accgctccat gctcctgggc aacgggcgct 19920
acgtgccctt ccacatccag gtgccccaaa agttcttcgc catcaagagc ctcctgctcc 19980
tgcccgggtc ctacacctac gagtggaact tccgcaagga cgtcaacatg atcctgcaga 20040
gctccctcgg caacgacctg cgcacggacg gggcctccat cgccttcacc agcatcaacc 20100
tctacgccac cttcttcccc atggcgcaca acaccgcctc cacgctcgag gccatgctgc 20160
gcaacgacac caacgaccag tccttcaacg actacctctc ggcggccaac atgctctacc 20220
ccatcccggc caacgccacc aacgtgccca tctccatccc ctcgcgcaac tgggccgcct 20280
tccgcggatg gtccttcacg cgcctcaaga cccgcgagac gccctcgctc ggctccgggt 20340
tcgaccccta cttcgtctac tcgggctcca tcccctacct cgacggcacc ttctacctca 20400
accacacctt caagaaggtc tccatcacct tcgactcctc cgtcagctgg cccggcaacg 20460
accgcctcct gacgcccaac gagttcgaaa tcaagcgcac cgtcgacgga gaggggtaca 20520
acgtggccca gtgcaacatg accaaggact ggttcctggt ccagatgctg gcccactaca 20580
acatcggcta ccagggcttc tacgtgcccg agggctacaa ggaccgcatg tactccttct 20640
tccgcaactt ccagcccatg agccgccagg tcgtggacga ggtcaactac aaggactacc 20700
aggccgtcac cctggcctac cagcacaaca actcgggctt cgtcggctac ctcgcgccca 20760
ccatgcgcca gggacagccc taccccgcca actaccccta cccgctcatc ggcaagagcg 20820
ccgtcgccag cgtcacccag aaaaagttcc tctgcgaccg ggtcatgtgg cgcatcccct 20880
tctccagcaa cttcatgtcc atgggcgcgc tcaccgacct cggccagaac atgctctacg 20940
ccaactccgc ccacgcgcta gacatgaatt tcgaagtcga ccccatggat gagtccaccc 21000
ttctctatgt tgtcttcgaa gtcttcgacg tcgtccgagt gcaccagccc caccgcggcg 21060
tcatcgaggc cgtctacctg cgcacgccct tctcggccgg caacgccacc acctaagccc 21120
cgctcttgct tcttgcaaga tgacggcctg tgcgggctcc ggcgagcagg agctcagggc 21180
catcctccgc gacctgggct gcgggccctg cttcctgggc accttcgaca agcgcttccc 21240
gggattcatg gccccgcaca agctggcctg cgccatcgtc aacacggccg gccgcgagac 21300
cgggggcgag cactggctgg ccttcgcctg gaacccgcgc tcccacacct gctacctctt 21360
cgaccccttc gggttctcgg acgagcgcct caagcagatc taccagttcg agtacgaggg 21420
cctgctgcgc cgcagcgccc tggccaccga ggaccgctgc gtcaccctgg aaaagtccac 21480
ccagaccgtg cagggtccgc gctcggccgc ctgcgggctc ttctgctgca tgttcctgca 21540
cgccttcgtg cactggcccg accgccccat ggacaagaac cccaccatga acttgctgac 21600
gggggtgccc aacggcatgc tccagtcgcc ccaggtggaa cccaccctgc gccgcaacca 21660
ggaggcgctc taccgcttcc tcaacgccca ctccgcctac tttcgctccc accgcgcgcg 21720
catcgagaag gccaccgcct tcgaccgcat gaatcaagac atgtaaaccg tgtgtgtatg 21780
tgaatgcttt attcataata aacagcacat gtttatgcca ccttttctga ggctctgact 21840
ttatttagaa atcgaagggg ttctgccggc tctcggcgtg ccccgcgggc agggatacgt 21900
tgcggaactg gtacttgggc agccacttga actcggggat cagcagcttc ggcacgggga 21960
ggtcggggaa cgagtcgctc cacagcttgc gcgtgagttg cagggcgccc agcaggtcgg 22020
gcgcggagat cttgaaatcg cagttgggac ccgcgttctg cgcgcgggag ttgcggtaca 22080
cggggttgca gcactggaac accatcaggg ccgggtgctt cacgctcgcc agcaccgtcg 22140
cgtcggtgat gccctccacg tccagatcct cggcgttggc catcccgaag ggggtcatct 22200
tgcaggtctg ccgccccatg ctgggcacgc agccgggctt gtggttgcaa tcgcagtgca 22260
gggggatcag catcatctgg gcctgctcgg agctcatgcc cgggtacatg gccttcatga 22320
aagcctccag ctggcggaag gcctgctgcg ccttgccgcc ctcggtgaag aagaccccgc 22380
aggacttgct agagaactgg ttggtggcgc agccggcgtc gtgcacgcag cagcgcgcgt 22440
cgttgttggc cagctgcacc acgctgcgcc cccagcggtt ctgggtgatc ttggcccggt 22500
cggggttctc cttcagcgcg cgctgcccgt tctcgctcgc cacatccatc tcgatcgtgt 22560
gctccttctg gatcatcacg gtcccgtgca ggcatcgcag cttgccctcg gcctcggtgc 22620
acccgtgcag ccacagcgcg cagccggtgc actcccagtt cttgtgggcg atctgggagt 22680
gcgagtgcac gaagccctgc aggaagcggc ccatcatcgt ggtcagggtc ttgttgctgg 22740
tgaaggtcag cgggatgccg cggtgctcct cgttcacata caggtggcag atgcggcggt 22800
acacctcgcc ctgctcgggc atcagctgga aggcggactt caggtcgctc tccacgcggt 22860
accggtccat cagcagcgtc atgacttcca tgcccttctc ccaggccgag acgatcggca 22920
ggctcagggg gttcttcacc gccgttgtca tcttagtcgc cgccgctgag gtcagggggt 22980
cgttctcgtc cagggtctca aacactcgct tgccgtcctt ctcggtgatg cgcacggggg 23040
gaaagctgaa gcccacggcc gccagctcct cctcggcctg cctttcgtcc tcgctgtcct 23100
ggctgatgtc ttgcaaaggc acatgcttgg tcttgcgggg tttctttttg ggcggcagag 23160
gcggcggcgg agacgtgctg ggcgagcgcg agttctcgct caccacgact atttcttctt 23220
cttggccgtc gtccgagacc acgcggcggt aggcatgcct cttctggggc agaggcggag 23280
gcgacgggct ctcgcggttc ggcgggcggc tggcagagcc ccttccgcgt tcgggggtgc 23340
gctcctggcg gcgctgctct gactgacttc ctccgcggcc ggccattgtg ttctcctagg 23400
gagcaacaag catggagact cagccatcgt cgccaacatc gccatctgcc cccgccgccg 23460
ccgacgagaa ccagcagcag aatgaaagct taaccgcccc gccgcccagc cccacctccg 23520
acgccgccgc ggccccagac atgcaagaga tggaggaatc catcgagatt gacctgggct 23580
acgtgacgcc cgcggagcac gaggaggagc tggcagcgcg cttttcagcc ccggaagaga 23640
accaccaaga gcagccagag caggaagcag agagcgagca gcagcaggct gggctcgagc 23700
atggcgacta cctgagcggg gcagaggacg tgctcatcaa gcatctggcc cgccaatgca 23760
tcatcgtcaa ggacgcgctg ctcgaccgcg ccgaggtgcc cctcagcgtg gcggagctca 23820
gccgcgccta cgagcgcaac ctcttctcgc cgcgcgtgcc ccccaagcgc cagcccaacg 23880
gcacctgcga gcccaacccg cgcctcaact tctacccggt cttcgcggtg cccgaggccc 23940
tggccaccta ccacctcttt ttcaagaacc aaaggatccc cgtctcctgc cgcgccaacc 24000
gcacccgcgc cgacgccctg ctcaacctgg gtcccggcgc ccgcctacct gatatcgcct 24060
ccttggaaga ggttcccaag atcttcgagg gtctgggcag cgacgagact cgggccgcga 24120
acgctctgca aggaagcgga gaggagcatg agcaccacag cgccctggtg gagttggaag 24180
gcgacaacgc gcgcctggcg gtgctcaagc gcacggtcga gctgacccac ttcgcctacc 24240
cggcgctcaa cctgcccccc aaggtcatga gcgccgtcat ggaccaggtg ctcatcaagc 24300
gcgcctcgcc cctctcggat gaggacatgc aggaccccga gagctcggac gagggcaagc 24360
ccgtggtcag cgacgagcag ctggcgcgct ggctgggagc gagtagcacc ccccagagct 24420
tggaagagcg gcgcaagctc atgatggccg tggtcctggt gaccgtggag ctggagtgtc 24480
tgcgccgctt cttcgccgac gcagagaccc tgcgcaaggt cgaggagaac ctgcactacc 24540
tcttcaggca cgggtttgtg cgccaggcct gcaagatctc caacgtggag ctgaccaacc 24600
tggtctccta catgggcatc ctgcacgaga accgcctggg gcagaacgtg ctgcacacca 24660
ccctgcgcgg ggaggcccgc cgcgactaca tccgcgactg cgtctacctg tacctctgcc 24720
acacctggca gacgggcatg ggcgtgtggc agcagtgcct ggaggagcag aacctgaaag 24780
agctctgcaa gctcctgcag aagaacctga aggccctgtg gaccgggttc gacgagcgca 24840
ccaccgcctc ggacctggcc gacctcatct tccccgagcg cctgcggctg acgctgcgca 24900
acggactgcc cgactttatg agtcaaagca tgttgcaaaa ctttcgctct ttcatcctcg 24960
aacgctccgg gatcctgccc gccacctgct ccgcgctgcc ctcggacttc gtgccgctga 25020
ccttccgcga gtgccccccg ccgctctgga gccactgcta cctgctgcgc ctggccaact 25080
acctggccta ccactcggac gtgatcgagg acgtcagcgg cgagggtctg ctcgagtgcc 25140
actgccgctg caacctctgc acgccgcacc gctccctggc ctgcaacccc cagctgctga 25200
gcgagaccca gatcatcggc accttcgagt tgcaaggccc cggcgagggc aaggggggtc 25260
tgaaactcac cccggggctg tggacctcgg cctacttgcg caagttcgtg cccgaggact 25320
accatccctt cgagatcagg ttctacgagg accaatccca gccgcccaag gccgaactgt 25380
cggcctgcgt catcacccag ggggccatcc tggcccaatt gcaagccatc cagaaatccc 25440
gccaagaatt tctgctgaaa aagggccacg gggtctacct ggacccccag accggagagg 25500
agctcaaccc cagcttcccc caggatgccc cgaggaagca gcaagaagct gaaagtggag 25560
ctgccgccgc cggaggattt ggaggaagac tgggagagca gtcaggcaga ggaggaggag 25620
atggaagact gggacagcac tcaggcagag gaggacagcc tgcaagacag tctggaagac 25680
gaggtggagg aggaggcaga ggaagaagca gccgccgcca gaccgtcgtc ctcggcggag 25740
aaagcaagca gcacggatac catctccgct ccgggtcggg gtcgcggcga ccgggcccac 25800
agtaggtggg acgagaccgg gcgcttcccg aaccccacca cccagaccgg taagaaggag 25860
cggcagggat acaagtcctg gcgggggcac aaaaacgcca tcgtctcctg cttgcaagcc 25920
tgcgggggca acatctcctt cacccgccgc tacctgctct tccaccgcgg ggtgaacttc 25980
ccccgcaaca tcttgcatta ctaccgtcac ctccacagcc cctactactg tttccaagaa 26040
gaggcagaaa cccagcagca gcagaaaacc agcggcagca gcagctagaa aatccacagc 26100
ggcggcaggt ggactgagga tcgcagcgaa cgagccggcg cagacccggg agctgaggaa 26160
ccggatcttt cccaccctct atgccatctt ccagcagagt cgggggcagg agcaggaact 26220
gaaagtcaag aaccgttctc tgcgctcgct cacccgcagt tgtctgtatc acaagagcga 26280
agaccaactt cagcgcactc tcgaggacgc cgaggctctc ttcaacaagt actgcgcgct 26340
cactcttaaa gagtagcccg cgcccgccca cacacggaaa aaggcgggaa ttacgtcacc 26400
acctgcgccc ttcgcccgac catcatcatg agcaaagaga ttcccacgcc ttacatgtgg 26460
agctaccagc cccagatggg cctggccgcc ggcgccgccc aggactactc cacccgcatg 26520
aactggctca gcgccgggcc cgcgatgatc tcacgggtga atgacatccg cgcccgccga 26580
aaccagatac tcctagaaca gtcagcgatc accgccacgc cccgccatca ccttaatccg 26640
cgtaattggc ccgccgccct ggtgtaccag gaaattcccc agcccacgac cgtactactt 26700
ccgcgagacg cccaggccga agtccagctg actaactcag gtgtccagct ggccggcggc 26760
gccgccctgt gtcgtcaccg ccccgctcag ggtataaagc ggctggtgat ccgaggcaga 26820
ggcacacagc tcaacgacga ggtggtgagc tcttcgctgg gtctgcgacc tgacggagtc 26880
ttccaactcg ccggatcggg gagatcttcc ttcacgcctc gtcaggccgt cctgactttg 26940
gagagttcgt cctcgcagcc ccgctcgggt ggcatcggca ctctccagtt cgtggaggag 27000
ttcactccct cggtctactt caaccccttc tccggctccc ccggccacta cccggacgag 27060
ttcatcccga acttcgacgc catcagcgag tcggtggacg gctacgattg aatgtcccat 27120
ggtggcgcag ctgacctagc tcggcttcga cacctggacc actgtcgcct ctcctacgag 27180
ctcctgcagc agcgccagaa gttcacctgc ctggtcggag tcaaccccat cgtcatcacc 27240
cagcagtcgg gcgataccaa ggggtgcatc cactgctcct gcgactcccc cgactgcgtc 27300
cacactctga tcaagaccct ctgcggcctc cgcgacctcc tccccatgaa ctaatcaccc 27360
ccttatccag tgaaataaag atcatattga tgatttgagt ttaataaaaa taaagaatca 27420
cttacttgaa atctgatacc aggtctctgt ccatgttttc tgccaacacc acttcactcc 27480
cctcttccca gctctggtac tgcaggcccc ggcgggctgc aaacttcctc cacaccctga 27540
aggggatgtc aaattcctcc tgtccctcaa tcttcatttt atcttctatc agatgtccaa 27600
aaagcgcgtc cgggtggatg atgacttcga ccccgtctac ccctacgatg cagacaacgc 27660
accgaccgtg cccttcatca accccccctt cgtctcttca gatggattcc aagagaagcc 27720
cctgggggtg ctgtccctgc gtctggccga tcccgtcacc accaagaacg gggaaatcac 27780
cctcaagctg ggagatgggg tggacctcga ctcctcggga aaactcatct ccaacacggc 27840
caccaaggcc gccgcccctc tcagtttttc caacaacacc atttccctta acatggatac 27900
ccctttttac aacaacaatg gaaagttagg catgaaagtc actgctccac tgaagatact 27960
agacacagac ttgctaaaaa cacttgttgt agcttatgga caaggtttag gaacaaacac 28020
cactggtgcc cttgttgccc aactagcatc cccacttgct tttgatagca atagcaaaat 28080
tgcccttaat ttaggcaatg gaccattgaa agtggatgca aatagactga acatcaattg 28140
caatagagga ctctatgtta ctaccacaaa agatgcactg gaagccaata taagttgggc 28200
taatgctatg acatttatag gaaatgccat gggtgtcaat attgatacac aaaaaggctt 28260
gcaatttggc accactagta ccgtcgcaga tgttaaaaac gcttacccca tacaaatcaa 28320
acttggagct ggtctcacat ttgacagcac aggtgcaatt gttgcatgga acaaagatga 28380
tgacaagctt acactatgga ccacagccga cccctctcca aattgtcaca tatattctga 28440
aaaggatgct aagcttacac tttgcttgac aaagtgtggc agtcagattc tgggcactgt 28500
ttccctcata gctgttgata ctggcagttt aaatcccata acaggaacag taaccactgc 28560
tcttgtctca cttaaattcg atgcaaatgg agttttgcaa agcagctcaa cactagactc 28620
agactattgg aatttcagac agggagatgt tacacctgct gaagcctata ctaatgctat 28680
aggtttcatg cccaatctaa aagcataccc taaaaacaca agtggagctg caaaaagtca 28740
cattgttggg aaagtgtacc tacatgggga tacaggcaaa ccactggacc tcattattac 28800
tttcaatgaa acaagtgatg aatcttgcac ttactgtatt aactttcaat ggcagtgggg 28860
ggctgatcaa tataaaaatg aaacacttgc cgtcagttca ttcacctttt cctatattgc 28920
taaagaataa accccactct gtaccccatc tctgtctatg gaaaaaactc tgaaacacaa 28980
aataaaataa agttcaagtg ttttattgat tcaacagttt tacaggattc gagcagttat 29040
ttttcctcca ccctcccagg acatggaata caccaccctc tccccccgca cagccttgaa 29100
catctgaatg ccattggtga tggacatgct tttggtctcc acgttccaca cagtttcaga 29160
gcgagccagt ctcgggtcgg tcagggagat gaaaccctcc gggcactccc gcatctgcac 29220
ctcacagctc aacagctgag gattgtcctc ggtggtcggg atcacggtta tctggaagaa 29280
gcagaagagc ggcggtggga atcatagtcc gcgaacggga tcggccggtg gtgtcgcatc 29340
aggccccgca gcagtcgctg tcgccgccgc tccgtcaagc tgctgctcag ggggtccggg 29400
tccagggact ccctcagcat gatgcccacg gccctcagca tcagtcgtct ggtgcggcgg 29460
gcgcagcagc gcatgcggat ctcgctcagg tcgctgcagt acgtgcaaca caggaccacc 29520
aggttgttca acagtccata gttcaacacg ctccagccga aactcatcgc gggaaggatg 29580
ctacccacgt ggccgtcgta ccagatcctc aggtaaatca agtggcgccc cctccagaac 29640
acgctgccca tgtacatgat ctccttgggc atgtggcggt tcaccacctc ccggtaccac 29700
atcaccctct ggttgaacat gcagccccgg atgatcctgc ggaaccacag ggccagcacc 29760
gccccgcccg ccatgcagcg aagagacccc gggtcccgac aatggcaatg gaggacccac 29820
cgctcgtacc cgtggatcat ctgggagctg aacaagtcta tgttggcaca gcacaggcat 29880
atgctcatgc atctcttcag cactctcagc tcctcggggg tcaaaaccat atcccagggc 29940
acggggaact cttgcaggac agcgaacccc gcagaacagg gcaatcctcg cacataactt 30000
acattgtgca tggacagggt atcgcaatca ggcagcaccg ggtgatcctc caccagagaa 30060
gcgcgggtct cggtctcctc acagcgtggt aagggggccg gccgatacgg gtgatggcgg 30120
gacgcggctg atcgtgttcg cgaccgtgtt atgatgcagt tgctttcgga cattttcgta 30180
cttgctgtag cagaacctgg tccgggcgct gcacaccgat cgccggcggc ggtcccggcg 30240
cttggaacgc tcggtgttga agttgtaaaa cagccactct ctcagaccgt gcagcagatc 30300
tagggcctca ggagtgatga agatcccatc atgcctgatg gctctaatca catcgaccac 30360
cgtggaatgg gccagaccca gccagatgat gcaattttgt tgggtttcgg tgacggcggg 30420
ggagggaaga acaggaagaa ccatgattaa cttttaatcc aaacggtctc ggagcacttc 30480
aaaatgaaga tcgcggagat ggcacctctc gcccccgctg tgttggtgga aaataacagc 30540
caggtcaaag gtgatacggt tctcgagatg ttccacggtg gcttccagca aagcctccac 30600
gcgcacatcc agaaacaaga caatagcgaa agcgggaggg ttctctaatt cctcaatcat 30660
catgttacac tcctgcacca tccccagata attttcattt ttccagcctt gaatgattcg 30720
aactagttcc tgaggtaaat ccaagccagc catgataaag agctcgcgca gagcgccctc 30780
caccggcatt cttaagcaca ccctcataat tccaagatat tctgctcctg gttcacctgc 30840
agcagattga caagcggaat atcaaaatct ctgccgcgat ccctaagctc ctccctcagc 30900
aataactgta agtactcttt catatcctct ccgaaatttt tagccatagg accaccagga 30960
ataagattag ggcaagccac agtacagata aaccgaagtc ctccccagtg agcattgcca 31020
aatgcaagac tgctataagc atgctggcta gacccggtga tatcttccag ataactggac 31080
agaaaatcgc ccaggcaatt tttaagaaaa tcaacaaaag aaaaatcctc caggtgcacg 31140
tttagagcct cgggaacaac gatggagtaa atgcaagcgg tgcgttccag catggttagt 31200
tagctgatct gtagaaaaaa acaaaaatga acattaaacc atgctagcct ggcgaacagg 31260
tgggtaaatc gttctctcca gcaccaggca ggccacgggg tctccggcac gaccctcgta 31320
aaaattgtcg ctatgattga aaaccatcac agagagacgt tcccggtggc cggcgtgaat 31380
gattcgacaa gatgaataca cccccggaac attggcgtcc gcgagtgaaa aaaagcgccc 31440
aaggaagcaa taaggcacta caatgctcag tctcaagtcc agcaaagcga tgccatgcgg 31500
atgaagcaca aaattctcag gtgcgtacaa aatgtaatta ctcccctcct gcacaggcag 31560
caaagccccc gatccctcca ggtacacata caaagcctca gcgtccatag cttaccgagc 31620
agcagcacac aacaggcgca agagtcagag aaaggctgag ctctaacctg tccacccgct 31680
ctctgctcaa tatatagccc agatctacac tgacgtaaag gccaaagtct aaaaataccc 31740
gccaaataat cacacacgcc cagcacacgc ccagaaaccg gtgacacact caaaaaaata 31800
cgcgcacttc ctcaaacgcc caaactgccg tcatttccgg gttcccacgc tacgtcatca 31860
aaattcgact ttcaaattcc gtcgaccgtt aaaaacgtcg cccgccccgc ccctaacggt 31920
cgccgctccc gcagccaatc accgccccgc atccccaaat tcaaatacct catttgcata 31980
ttaacgcgca ccaaaagttt gaggtatatt attgatgatg 32020
<210> 6
<211> 1737
<212> DNA
<213> 黑猩猩腺病毒- ChAd 20纤维
<400> 6
atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60
agcggccctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120
gaaagtcccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180
atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgctggcaa cctcacctct 240
caagatatca ccaccgctag ccctcccctc aaaaaaacca agaccaacct cagcctagaa 300
acctcatccc ccctaactgt gagcacctca ggcgccctca ccgtagcagc cgccgctccc 360
ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtacaggat 420
gcaaaactca ccctggccac caaaggcccc ctgaccgtgt ctgaaggcaa actggccttg 480
caaacatcgg ccccgctgac ggccgctgac agcagcaccc tcacagtcag tgccacacca 540
ccccttagca caagcaatgg cagcttgggt attgacatgc aagcccccat ttacaccacc 600
aatggaaaac taggacttaa ctttggcgct cccctgcatg tggtagacag cctaaatgca 660
ctgactgtag ttactggcca aggtcttacg ataaacggaa cagccctaca aactagagtc 720
tcaggtgccc tcaactatga cacatcagga aacctagaat tgagagctgc agggggtatg 780
cgagttgatg caaatggtca acttatcctt gatgtagctt acccatttga tgcacaaaac 840
aatctcagcc ttaggcttgg acagggaccc ctgtttgtta actctgccca caacttggat 900
gttaactaca acagaggcct ctacctgttc acatctggaa ataccaaaaa gctagaagtt 960
aatatcaaaa cagccaaggg tctcatttat gatgacactg ctatagcaat caatgcgggt 1020
gatgggctac agtttgactc aggctcagat acaaatccat taaaaactaa acttggatta 1080
ggactggatt atgactccag cagagccata attgctaaac tgggaactgg cctaagcttt 1140
gacaacacag gtgccatcac agtaggcaac aaaaatgatg acaagctcac cttgtggacc 1200
acaccagacc catctcctaa ctgtagaatc tattcagaga aagatgctaa attcacactt 1260
gttttgacta aatgcggcag tcaggtgttg gccagcgttt ctgttttatc tgtaaaaggt 1320
agccttgcgc ccatcagtgg cacagtaact agtgctcaga ttgtcctcag atttgatgaa 1380
aatggagttc tactaagcaa ttcttccctt gaccctcaat actggaacta cagaaaaggt 1440
gaccttacag agggcactgc atataccaac gcagtgggat ttatgcccaa cctcacagca 1500
tacccaaaaa cacagagcca aactgctaaa agcaacattg taagtcaggt ttacttgaat 1560
ggggacaaat ccaaacccat gaccctcacc attaccctca atggaactaa tgaaacagga 1620
gatgccacag taagcactta ctccatgtca ttctcatgga actggaatgg aagtaattac 1680
attaatgaaa cgttccaaac caactccttc accttctcct acatcgccca agaataa 1737
<210> 7
<211> 1278
<212> DNA
<213> 黑猩猩腺病毒- ChAd 4纤维
<400> 7
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgatt cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360
aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420
ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480
aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540
aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600
aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660
caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720
aaagaagacg ataaactcac tttgtggaca acacctgatc catcaccaaa ctgtcaaata 780
ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840
gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900
agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960
acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020
aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080
aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140
actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200
acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260
tacatcgccc aagaatga 1278
<210> 8
<211> 1335
<212> DNA
<213> 黑猩猩腺病毒- ChAd 5纤维
<400> 8
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgct gtccctgcgt ctggccgatc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agatggggtg gacctcgacg actcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360
aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420
acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480
agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540
attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600
agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660
aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc tttttcactc 720
caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780
aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840
tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcaaatccta 900
ggcactgtct ccctattagc agtcagtggc agcttggctc ctatcacagg ggctgttaga 960
actgcacttg tatcactcaa attcaatgct aatggagccc ttttggacaa atcaactctg 1020
aacaaagaat actggaacta cagacaagga gatctaattc caggtacacc atatacacat 1080
gctgtgggtt tcatgcctaa caaaaaagcc taccctaaaa acacaactgc agcttccaag 1140
agccacattg tgggtgatgt gtatttagat ggagatgcag ataaaccttt atctcttatc 1200
atcactttca atgaaactga tgatgaaacc tgtgattact gcatcaactt tcaatggaaa 1260
tggggagctg atcaatataa ggataagaca ctcgcaacca gttcattcac cttctcatac 1320
atcgcccaag aataa 1335
<210> 9
<211> 1338
<212> DNA
<213> 黑猩猩腺病毒- ChAd 7纤维
<400> 9
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggataccc ctttttacaa caataatgga aagttaggca tgaaagtcac tgctccactg 360
aagatactcg acacagactt gctaaaaaca cttgttgtag cttatggaca aggtttagga 420
acaaacacca ctggtgccct tgttgcccaa ctagcagccc cacttgcttt tgatagcaat 480
agcaaaattg cccttaattt aggcaatgga ccattgaaag tggatgcaaa tagactgaac 540
atcaattgca atagaggact ctatgttact accacaaaag atgcactgga aaccaacata 600
agttgggcta atgctatgac atttatagga aatgccatgg gtgtcaatat tgatacacaa 660
aaaggcttgc aatttggcac cactagtacc gtcgcagatg ttaaaaacgc ttaccccata 720
caagtcaaac tgggagctgg tctcacattt gacagcacag gtgcaattgt cgcttggaac 780
aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840
tattctgaca aggatgctaa gcttacactc tgcttgacaa agtgtggcag tcagatactg 900
ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggacaagta 960
accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaaac cagttcaaca 1020
ttggacaaag aatattggaa ttttagaaaa ggagatgtga cacctgctga gccatatact 1080
aatgctatag gtttcatgcc caatctaaag gcatacccta aaaacacaag tggagctgca 1140
aaaagtcaca ttgttgggaa agtgtaccta catggggata cagacaaacc actggacctg 1200
attattactt tcaatgaaac aagtgatgaa tcttgcactt actgtattaa ctttcaatgg 1260
aaatgggata gtactaagta cacaggtgaa acacttgcta caagctcctt caccttctcc 1320
tacattgccc aagaatga 1338
<210> 10
<211> 1278
<212> DNA
<213> 黑猩猩腺病毒- ChAd 9纤维
<400> 10
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc tgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggatcacc ccttttacac taaagatgga aaattagcct tacaagtttc tccaccatta 360
aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420
ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480
aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540
aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600
aatgggttag agtttggaag cagtagtaca gaaacaggtg tcgatgatgc ttacccaatc 660
caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720
aaagaagacg ataaactcac tttgtggaca acacctgatc catcaccaaa ctgtcaaata 780
ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840
gccactgtgt cagtcttagt tgtaggaagt ggagacctaa accccattac tggcaccgta 900
agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960
acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatgcc 1020
aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080
aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140
actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200
acctggacta atggaagcta tgttggagca acatttggag ctaactctta taccttctcc 1260
tacatcgccc aagaatga 1278
<210> 11
<211> 1278
<212> DNA
<213> 黑猩猩腺病毒- ChAd 10纤维
<400> 11
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360
aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420
ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480
aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540
aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600
aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660
caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720
aaagaagacg ataaactcac tttgtggaca acacctgatc catcgccaaa ctgtcaaata 780
ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840
gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900
agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960
acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020
aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080
aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140
actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200
acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260
tacatcgccc aagaatga 1278
<210> 12
<211> 1737
<212> DNA
<213> 黑猩猩腺病毒- ChAd 11纤维
<400> 12
atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60
aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120
gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180
atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240
caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300
acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgttccc 360
ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420
gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actagccttg 480
cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcacaatcag cgccacaccg 540
ccccttagca caagcaatgg cagcttgggt attgacatgc aagcccccat ttacactact 600
aacggaaaac tgggacttaa ctttggtgct cccctgcatg tggtagacag cctaaatgca 660
ctgactgtag tgactggcca aggtcttacg ataaacggta cagccctaca aactagagtc 720
tcaggtgccc tcaactatga ctcatcagga aacctagaat tgagagctgc agggggtatg 780
cgagttgatg caaatggcaa acttatcctt gacgtagctt acccatttga tgctcaaaac 840
aacctcagcc ttagacttgg acagggaccc ctgtttgtta actctgccca caacttggat 900
gttaactaca acagaggcct ctacctgttc acatctggaa ataccaaaaa gctagaagtt 960
aatatcaaaa cagccaaagg cctcatttat gatgacactg ctatagcaat caatccaggc 1020
gatgggctag agtttggctc aggctcagat acaaatccat taaaaactaa acttggattg 1080
ggactagagt atgactccag cagagccata attgctaagc tgggaaccgg cctaagcttt 1140
gacaacacag gtgccatcac agtgggcaac aaaaatgatg acaagcttac cttgtggacc 1200
acaccagacc cctctcccaa ctgtagaatt tattcagaaa aagatgctaa atttacacta 1260
gttttaacta aatgcggcag tcaggtgttg gccagcgttt ctgttttatc tgtaaaaggc 1320
agccttgcgc ccatcagtgg cacagtaact agcgctcaga ttattctcag atttgatgaa 1380
aatggagttc tactaagcaa ttcttctctt gacccccaat actggaacta cagaaaaggt 1440
gaccttacag agggcactgc atataccaac gcagtgggat ttatgcccaa cctcacagca 1500
tacccaaaaa cacagagtca aactgctaaa agcaacattg taagccaggt ttacttgaat 1560
ggggacaaat ccaaacccat gatcctcacc attaccctca atggaactaa tgaaacaggg 1620
gatgctacag ttagcactta ctccatgtca ttctcatgga attggaatgg aagtaattac 1680
attaatgaaa cgttccaaac caactctttc accttctcct acatcgccca agaataa 1737
<210> 13
<211> 1632
<212> DNA
<213> 黑猩猩腺病毒- ChAd 16纤维
<400> 13
atgaagcgca ccaaaacgtc tgacaagagc ttcaaccccg tgtaccccta tgacacggaa 60
aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120
gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180
atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240
caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300
acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgccccc 360
ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420
gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actggccttg 480
cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag cgccacacca 540
cccatcagtg taagcagtgg aagtttgggc ttagacatgg aagacccaat gtatactcat 600
gatggaaaac tgggaataag aattgggggc ccactgagag tagtagacag cctgcacaca 660
ctgactgtag ttaccggaaa tggaatagct gtagataaca atgccctcca aactagagtt 720
acgggcgccc tgggttatga cacatcagga aacctacaac tgagagccgc ggggggtatg 780
cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840
aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa acacagacca caacctagat 900
ttgaattgca acagaggtct gaccacaact accaccaaca acacaaaaaa acttgaaact 960
aaaattggct caggcttaga ctatgatacc aatggtgctg ttattattaa acttggcact 1020
ggtgtcagct ttgacagcac aggtgcccta agtgtgggaa acactggcga tgataaactg 1080
actctgtgga caaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140
aagtttactc tagtcctaac taagtgtgga agtcaaatcc tggcttctgt cgccgcccta 1200
gcggtgtcag gaaatctggc ttcaataaca ggcaccgttt ccagcgttac catctttctc 1260
agatttgatc agaatggagt gcttatggaa aactcctcgc tagacaagca gtactggaac 1320
ttcagaaatg gtaattcaac caatgccacc ccctacacca atgcagttgg gtttatgcca 1380
aacctcgcag cataccccaa gacacagagc cagactgcaa aaaacaacat tgtaagtcag 1440
gtttacttga atggggacaa atccaaaccc atgaccctta ccattaccct caatggaact 1500
aatgaatcca gtgaaactag ccaggtgagt cactactcca tgtcatttac gtgggcttgg 1560
gagagtgggc aatatgccac cgaaaccttt gccaccaatt cctttacctt ctcttacatt 1620
gctgaacaat aa 1632
<210> 14
<211> 1632
<212> DNA
<213> 黑猩猩腺病毒-ChAd 17纤维
<400> 14
atgaagcgca ccaaaacgtc tgacgagagc ttcaaccccg tgtaccccta tgacacggaa 60
agcggccctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120
gaaagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180
atgcttgccc tgaaaatggg aagtggcctc tccctggacg acgctggcaa ccttacctct 240
caagatatta cctccactac ccctcccctc aaaaaaacca agaccaacct cagcctagaa 300
acctcatccc ccctaactgt aagcacctca ggcgccctca ccgtagcagc cgccgctccc 360
ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctggc agtacaggat 420
gcaaaactca ccctggccac caaaggcccc ctgaccgtgt ctgaaggcaa actggccttg 480
caaacatcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag ctccactcca 540
ccaattagtg taagcagtgg aagtttgggc ttggacatgg aagaccccat gtatactcac 600
gatggaaaac tgggaataag aattgggggt ccactaagag tagtagacag cttgcacaca 660
ctcactgtag ttaccggaaa tggactaact gtagataaca atgccctcca aactagagtt 720
acgggcgccc taggttatga cacatcagga aatctacaac tgagagccgc agggggtatg 780
cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840
aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa atacagacca caacctggat 900
ttaaattgca acagaggtct aaccacaact accaccaaca acacaaaaaa acttgagact 960
aaaattagct caggcttaga ctatgacacc aatggtgctg tcattattaa acttggcact 1020
ggtctaagct tcgacaacac aggcgcccta actgtgggaa acactggtga tgataaactg 1080
actctgtgga cgaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140
aagtttactc tcgtcctaac taagtgtgga agccaaatcc tggcctctgt cgccgcccta 1200
gcggtatcag gaaatctggc ttcgataaca ggcaccgttg ccagcgttac catctttctt 1260
agatttgatc agaatggagt gcttatggaa aactcctcac tagacaagca gtactggaac 1320
ttcagaaatg gcaattcaac taatgctgcc ccctacacca acgcagttgg gttcatgcca 1380
aacctcgcag cgtaccccaa aacgcaaagc cagactgcta aaaacaacat tgtaagtcag 1440
gtttacttga atggagacaa atccaaaccc atgaccctta ccatcaccct caatggaact 1500
aatgaatcca gtgaaactag tcaggtgagt cactactcca tgtcatttac atgggcttgg 1560
gaaagcgggc aatatgccac tgaaaccttt gccaccaact ccttcacctt ttcttacatt 1620
gctgaacaat aa 1632
<210> 15
<211> 1632
<212> DNA
<213> 黑猩猩腺病毒- ChAd 19纤维
<400> 15
atgaagcgca ccaaaacgtc tgacaagagc ttcaaccccg tgtaccccta tgacacggaa 60
aacggtcctc cctccgtccc tttcctcacc cctcccttcg tgtctcccga tggattccaa 120
gagagccccc ccggggtcct gtctctgaac ctggccgagc ccctggtcac ttcccacggc 180
atgctcgccc tgaaaatggg aagtggcctc tccctggacg acgccggcaa cctcacctct 240
caagatgtca ccaccactac ccctcccctg aaaaaaacca agaccaacct cagcctagaa 300
acctcagccc ccctgactgt gagcacctca ggcgccctca ccctagcagc cgccgccccc 360
ctggcggtgg ccggcacctc cctcaccatg caatcagagg cccccctgac agtccaagat 420
gcaaaactca ccctggccac caagggcccc ctgaccgtgt ctgaaggcaa actggccttg 480
cagacctcgg ccccgctgac ggccgctgac agcagcaccc tcaccgttag cgccacacca 540
cccatcagtg taagcagtgg aagtttgggc ttagacatgg aagacccaat gtatactcat 600
gatggaaaac tgggaataag aattgggggc ccactgagag tagtagacag cctgcacaca 660
ctgactgtag ttaccggaaa tggaatagct gtagataaca atgccctcca aactagagtt 720
acgggcgccc tgggttatga cacatcagga aacctacaac tgagagccgc ggggggtatg 780
cgaattgatg caaatggcca acttatcctt gatgtggcat acccatttga tgctcaaaac 840
aatctcagcc ttagacttgg tcagggaccc ctgtatgtaa acacagacca caacctagat 900
ttgaattgca acagaggtct gaccacaact accaccaaca acacaaaaaa acttgaaact 960
aaaattggct caggcttaga ctatgatacc aatggtgctg ttattattaa acttggcact 1020
ggtgtcagct ttgacagcac aggtgcccta agtgtgggaa acactggcga tgataaactg 1080
actctgtgga caaccccaga cccatctcca aattgcagaa ttcactcaga caaagactgc 1140
aagtttactc tagtcctaac taagtgtgga agtcaaatcc tggcttctgt cgccgcccta 1200
gcggtgtcag gaaatctggc ttcaataaca ggcaccgttt ccagcgttac catctttctc 1260
agatttgatc agaatggagt gcttatggaa aactcctcgc tagacaagca gtactggaac 1320
ttcagaaatg gtaattcaac caatgccacc ccctacacca atgcagttgg gtttatgcca 1380
aacctcgcag cataccccaa gacacagagc cagactgcaa aaaacaacat tgtaagtcag 1440
gtttacttga atggggacaa atccaaaccc atgaccctta ccattaccct caatggaact 1500
aatgaatcca gtgaaactag ccaggtgagt cactactcca tgtcatttac gtgggcttgg 1560
gagagtgggc aatatgccac cgaaaccttt gccaccaatt cctttacctt ctcttacatt 1620
gctgaacaat aa 1632
<210> 16
<211> 2865
<212> DNA
<213> 黑猩猩腺病毒- ChAd 20六邻体
<400> 16
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360
tacaactccc tggcccccaa gggcgctccc aacccatgcg agtgggatga ggctgctact 420
gcccttgaca ttgatttgaa cgcagaagac gatgaagaaa gcgacgaagc tcaaggggaa 480
gcagatcagc agaaaactca tgtatttggc caggcgccct actccggaca gaacattaca 540
aaagaaggca tacagatagg catagatgct gccagtcaag cccagacacc tgtatatgcc 600
gataaaacat tccaaccaga acctcaagtt ggagaatcac agtggaatga gacagagatt 660
agttatggag cgggacgggt gcttaaaaaa accactctca tgaaaccttg ctatgggtcg 720
tatgcaaggc ctactaatga gaacggaggt cagggcatcc tcttggaaca agatggaaag 780
aaagaaagtc aagtggaaat gcaatttttc tctactactc aggcagccgc gggtaattca 840
gataatccta ccccaaaggt tgttttgtac agcgaggatg ttaacctgga aacaccagat 900
acacacattt catacatgcc caccaacaac gagacaaatt caagagagct tttgggacaa 960
caggccatgc ccaacaggcc taattacatt ggcttcagag acaactttat cggtctcatg 1020
tattacaaca gcactggcaa catgggagtg cttgcaggtc aggcctctca gttgaacgca 1080
gtggtggact tgcaagacag aaacacagaa ctgtcatacc agctcttgct tgattccatg 1140
ggtgacagaa ccagatactt ttccatgtgg aatcaggcag tggacagtta tgacccagat 1200
gtcagaatta ttgaaaatca tggaactgaa gacgagctcc ccaactattg tttccctctg 1260
ggcggcgtaa tcaatacgga aactttcaca aaagtaaaac ctaaagctgc acaggacgct 1320
cagtgggaaa aagattcaga attttcagat aaaaatgaaa taagggtggg aaacaacttc 1380
gccatggaaa ttaacctcaa tgccaatctg tggaggaact ttttgtactc caacgtagcc 1440
ctctacttgc ctgacaagct taagtatact ccatccaatg tgcaaatttc caacaatccc 1500
aactcctacg attacatgaa caagcgagtg gtggccccgg ggctggtgga ctgctacatc 1560
aacctgggcg cgcgctggtc gctggactac atggacaacg tcaacccctt caaccaccac 1620
cgcaatgcgg gcctgcgcta ccgctccatg ctcctgggca acgggcgcta cgtgcccttc 1680
cacatccagg tgccccagaa gttctttgcc atcaagaacc tcctcctcct gccgggctcc 1740
tacacctacg agtggaactt caggaaggat gtcaacatgg tcctccagag ctctctgggt 1800
aacgatctca gggtggacgg ggccagcatc aagttcgaga gcatctgcct ctacgccacc 1860
ttcttcccca tggcccacaa cacggcctcc acgctcgagg ccatgctcag gaacgacacc 1920
aacgaccagt ccttcaatga ctacctttcc gccgccaaca tgctctaccc catacccgcc 1980
aacgccacca acgtccccat ctccatcccc tcgcgcaact gggcggcctt ccgcggctgg 2040
gccttcaccc gcctcaagac caaggagacc ccctccctgg gctcgggatt cgacccctac 2100
tacacctact cgggctccat tccctacctg gacggcacct tctacctcaa ccacactttc 2160
aagaaggtct cggtcacctt cgactcctcg gtcagctggc cgggcaacga ccgtctgctc 2220
acccccaacg agttcgagat caagcgctcg gtcgacgggg agggctacaa cgtggcccag 2280
tgcaacatga ccaaggactg gttcctggtc cagatgctgg ccaactacaa catcggctac 2340
cagggcttct acatcccaga gagctacaag gacaggatgt actccttctt caggaacttc 2400
cagcccatga gccggcaggt ggtggaccag accaagtaca aggactacca ggaggtgggc 2460
atcatccacc agcacaacaa ctcgggcttc gtgggctacc tcgcccccac catgcgcgag 2520
ggacaggcct accccgccaa cttcccctac ccgctcatag gcaagaccgc ggtcgacagc 2580
atcacccaga aaaagttcct ctgcgaccgc accctctggc gcatcccctt ctccagcaac 2640
ttcatgtcca tgggtgcgct ctcggacctg ggccagaact tgctctacgc caactccgcc 2700
cacgccctcg acatgacctt cgaggtcgac cccatggacg agcccaccct tctctatgtt 2760
ctgttcgaag tctttgacgt ggtccgggtc caccagccgc accgcggcgt catcgagacc 2820
gtgtacctgc gtacgccctt ctcggccggc aacgccacca cctaa 2865
<210> 17
<211> 2823
<212> DNA
<213> 黑猩猩腺病毒- ChAd 4六邻体
<400> 17
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaaaaagact 420
ggcaataatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480
attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tgacgataat 540
gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600
gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660
tatggctcat ttgccagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720
ggagatgtta agtcatttga catagaccta gccttctttg atattcccaa ttctggcgcg 780
ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840
ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctcaaag 900
gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960
tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020
tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080
ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140
agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200
tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260
actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320
tgcaaaggca atatctatgc catggagatc aacctccagg ccaacctgtg gagaagtttt 1380
ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440
accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500
ctggtggacg cctacatcaa catcggggcg cgctggtcgc tggaccccat ggacaacgtg 1560
aatcccttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1620
gggcgctacg tgcccttcca catccaggtg ccccagaaat ttttcgccat caagagcctc 1680
ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740
ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800
atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860
atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920
ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980
gccgccttcc gcggctggtc cttcacgcgc ctcaagaccc gcgagacgcc ctcgctgggc 2040
tccgggttcg acccctactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100
tacctcaacc acaccttcaa gaaggtctcc atcaccttcg actcctccgt cagctggccc 2160
ggcaacgacc gcctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggagag 2220
ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280
cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340
tccttcttcc gcaacttcca gcccatgagc cgccaggtgg tggacgaggt caactacaag 2400
gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460
gcgcccacca tgcgccaggg ccagccctac cccgccaact acccgtaccc gctcatcgga 2520
aagagcgccg tcaccagcgt cacccagaaa aagttcctct gcgacagggt catgtggcgc 2580
atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg ccagaacatg 2640
ctctatgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700
tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760
cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa cgccaccacc 2820
taa 2823
<210> 18
<211> 2823
<212> DNA
<213> 黑猩猩腺病毒- ChAd 5六邻体
<400> 18
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaaaaagact 420
ggcaataatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480
attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tgacgataat 540
gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600
gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660
tatggctcat ttgccagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720
ggagatgtta agtcatttga catagaccta gccttctttg atattcccaa ttctggcgcg 780
ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840
ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctcaaag 900
gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960
tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020
tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080
ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140
agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200
tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260
actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320
tgcaaaggca atatctatgc catggagatc aacctccagg ccaacctgtg gagaagtttt 1380
ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440
accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500
ctggtggacg cctacatcaa catcggggcg cgctggtcgc tggaccccat ggacaacgtg 1560
aatcccttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1620
gggcgctacg tgcccttcca catccaggtg ccccagaaat tttttgccat caagagcctc 1680
ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740
ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800
atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860
atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920
ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980
gccgccttcc gcggctggtc cttcacgcgc ctcaagaccc gcgagacgcc ctcgctgggc 2040
tccgggttcg acccctactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100
tacctcaacc acaccttcaa gaaggtctcc atcaccttcg actcctccgt cagctggccc 2160
ggcaacgacc gcctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggagag 2220
ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280
cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340
tccttcttcc gcaacttcca gcccatgagc cgccaggtcg tggacgaggt caactacaag 2400
gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460
gcgcccacca tgcgccaggg ccagccctac cccgccaact acccctaccc gctcatcggc 2520
aagagcgccg tcgccagcgt cacccagaaa aagttcctct gcgaccgggt catgtggcgc 2580
atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg ccagaacatg 2640
ctctacgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700
tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760
cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa agccaccacc 2820
taa 2823
<210> 19
<211> 2823
<212> DNA
<213> 黑猩猩腺病毒- ChAd 7六邻体
<400> 19
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccttactc cggcaccgct 360
tacaacagcc tggcccccaa gggagcaccc aattccagcc agtgggagca aaaaaagact 420
ggcaaaaatg ccaatggaga tacggagaat gtcacttatg gtgtagctgc catgggagga 480
attgacatcg ataaaaatgg ccttcaaatt ggaaccgatg acaccaaaga tggcgataat 540
gaaatttatg cagacaaaac atatcagcct gagccgcaaa taggagagga aaactggcaa 600
gaaacatatt cctactatgg aggtagagct cttaaaaaag ataccaaaat gaagccatgc 660
tatggctcat ttgctagacc taccaatgtg aaaggaggac aggcaaaaat aaaaacagat 720
ggagatgtta agtcatttga catagaccta gccttctttg atattccaaa ttctggcgcg 780
ggaaatggca caaatgttaa cgatgatcca gatatggtta tgtatacaga aaatgtaaat 840
ctggaaaccc cagatactca tattgtgtac aaaccaggaa cttcagatga cagctccgag 900
gtcaacttgt gtcagcaatc catgcctaac agacccaatt atattggctt cagagacaat 960
tttattgggc ttatgtacta caacagcact ggcaatatgg gtgtgctggc tggtcaggcc 1020
tctcaactga atgccgtggt ggacttgcaa gacagaaaca cagagctgtc ctaccagctc 1080
ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 1140
agttatgatc ctgatgtgcg cattattgaa aaccatggtg tggaggatga attgccaaac 1200
tattgcttcc ccttggatgg agcaggcacc aattcggttt accaaggtgt taaaccaaaa 1260
actgacaatg gcaacgatca gtgggaaaca gattccacag tttcaagtca caatcagata 1320
tgcaaaggca atatctatgc catggagatc aatctccagg ccaacctgtg gagaagtttc 1380
ctctactcga acgtggccct gtacctgccc gattcttaca agtacacgcc ggccaacatc 1440
accctgccca ccaacaccaa cacctacgat tacatgaacg ggagagtggt gcctccctcg 1500
ctggtggatg cctacatcaa catcggagcg cgctggtcgc tggaccccat ggacaacgtc 1560
aatcccttca accaccaccg caatgcgggg ctgcgctacc gctccatgct cctgggcaac 1620
gggcgctacg tgcccttcca catccaggtg ccccagaaat ttttcgccat caagagcctt 1680
ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt caacatgatc 1740
ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatctc cttcaccagc 1800
atcaacctct acgccacctt cttccccatg gcgcacaaca cggcctccac gctcgaggcc 1860
atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc ggccaacatg 1920
ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc gcgcaactgg 1980
gccgccttcc gcggctggtc cttcacgcgc ctcaagacca aggagacgcc ctcgctgggc 2040
tccgggttcg acccatactt cgtctactcg ggctccatcc cctacctcga cggcaccttc 2100
tacctcaacc acaccttcaa gaaggtctcc atcaccttcg attcctccgt cagctggccc 2160
ggcaacgacc ggctcctgac gcccaacgag ttcgaaatca agcgcaccgt cgacggcgag 2220
ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2280
cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga ccgcatgtac 2340
tccttcttcc gcaacttcca gcccatgagc cgccaggtgg tggacgaggt caactacaag 2400
gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt cggctacctc 2460
gcgcccacca tgcgccaggg ccagccctac cccgccaact acccgtaccc gctcatcggc 2520
aagagcgccg tcaccagcgt cacccagaaa aagttcctct gcgacagggt catgtggcgc 2580
atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg gcagaacatg 2640
ctctatgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc catggatgag 2700
tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca ccagccccac 2760
cgcggcgtca tcgaggccgt ctacctgcgc acccccttct cggccggtaa cgccaccacc 2820
taa 2823
<210> 20
<211> 2793
<212> DNA
<213> 黑猩猩腺病毒- ChAd 9六邻体
<400> 20
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcacccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgct 360
tacaacagcc tggctcccaa gggagcgccc aacacttgcc agtggacata tactgataac 420
caaactgaga aaacagccac atatggaaat gcacccgtag agggcattaa cattacaaaa 480
gatggcattc aacttggaac tgacagcgat ggtcaggcaa tctatgcaga cgaaacttat 540
cagcccgaac ctcaggtggg agatcctgaa tggcatgata ccacaggtac agaagaaaaa 600
tatggaggca gagcgcttaa acctgccacc gacatgaaac cttgctatgg ctcttttgcc 660
aagccaacta atgttaaggg aggtcaggcc aaaagcagaa caaaaactga tggaacaact 720
gagcctgata ttgacatggc cttttttgat ggcagaaatg caacaacagc tggtttgact 780
ccagaaattg ttttgtatac tgaaaatgtg gatctggaaa ctccagatac ccatattgta 840
tacaaggcag gcacagatga cagcagctct tctatcaatt tgggtcagca gtccatgccc 900
aacagaccca actacattgg cttcagagac aactttatcg ggctcatgta ctacaacagc 960
actggcaata tgggtgtact ggctggacag gcctcccagc tgaatgctgt ggtggacttg 1020
caggacagaa acactgaact gtcctaccag ctcttgcttg actctctggg tgacagaacc 1080
aggtatttca gtatgtggaa tcaggcggtg gacagttatg accccgatgt gcgcattatt 1140
gaaaatcacg gtgtggagga tgaactcccc aactattgct tccccctgaa tgctgtgggt 1200
agaacaaata gttatcaggg aattaaaccc aatggaggcg atccagctac atgggccaaa 1260
gatgaaagcg tcaatgattc taatgaattg ggcaagggca atcctttcgc catggagatc 1320
aacatccagg ccaacctgtg gcggaacttc ctctacgcga acgtggcgct gtacctgccc 1380
gactcctaca agtacacgcc ggccaacatc acgctgcccg ccaacaccaa cacctacgat 1440
tacatgaacg gccgcgtggt ggcgccctcg ctggtggacg cctacatcaa catcggggcg 1500
cgctggtcgc tggaccccat ggacaacgtc aaccccttca accaccaccg caacgcgggc 1560
ctgcgctacc gctccatgct cctgggcaac gggcgctacg tgcccttcca catccaggtg 1620
ccccaaaagt ttttcgccat caagagcctc ctgctcctgc ccgggtccta cacctacgag 1680
tggaacttcc gcaaggacgt caacatgatc ctgcagagct ccctcggcaa cgacctgcgc 1740
acggacgggg cctccatcgc cttcaccagc atcaacctct acgccacctt cttccccatg 1800
gcgcacaaca ccgcctccac gctcgaggcc atgctgcgca acgacaccaa cgaccagtcc 1860
ttcaacgact acctctcggc ggccaacatg ctctacccca tcccggccaa cgccaccaac 1920
gtgcccatct ccatcccctc gcgcaactgg gccgccttcc gcggatggtc cttcacgcgc 1980
ctcaagaccc gcgagacgcc ctcgctaggc tccgggttcg acccctactt cgtctactcg 2040
ggctccatcc cctacctcga cggcaccttc tacctcaacc acaccttcaa gaaggtctcc 2100
atcaccttcg actcctccgt cagctggccc ggcaacgacc gcctcctgac gcccaacgag 2160
ttcgaaatca agcgcaccgt cgacggagag ggatacaacg tggcccagtg caacatgacc 2220
aaggactggt tcctggtcca gatgctggcc cactacaaca tcggctacca gggcttctac 2280
gtgcccgagg gctacaagga ccgcatgtac tccttcttcc gcaacttcca gcccatgagc 2340
cgccaggtcg tggacgaggt caactacaag gactaccagg ccgtcaccct ggcctaccag 2400
cacaacaact cgggcttcgt cggctacctc gcgcccacca tgcgccaggg ccagccctac 2460
cccgccaact acccctaccc gctcatcggc aagagcgccg tcgccagcgt cacccagaaa 2520
aagttcctct gcgaccgggt catgtggcgc atccccttct ccagcaactt catgtccatg 2580
ggcgcgctca ccgacctcgg ccagaacatg ctctacgcca actccgccca cgcgctagac 2640
atgaatttcg aagtcgaccc catggatgag tccacccttc tctatgttgt cttcgaagtc 2700
ttcgacgtcg tccgagtgca ccagccccac cgcggcgtca tcgaggccgt ctacctgcgc 2760
acgcccttct cggccggcaa cgccaccacc taa 2793
<210> 21
<211> 2793
<212> DNA
<213> 黑猩猩腺病毒- ChAd 10六邻体
<400> 21
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggctcccaa gggagcgccc aacacttgcc agtggacata tactgataac 420
caaactgaga aaacagccac atatggaaat gcgcctgtgc aaggcattag tattacaaaa 480
gatggtattc aacttggaac tgacactgat gatcagccca tttatgcaga taaaacttat 540
caaccagagc ctcaagtggg tgatgctgaa tggcatgaca tcactggtac tgatgaaaaa 600
tatggaggca gagctctcaa gcctgacacc aaaatgaagc cctgctatgg ttcttttgcc 660
aagcctacca ataaagaagg aggtcaggca aatgtgaaaa ccgaaacagg cggtaccaaa 720
gaatatgaca ttgacatggc attcttcgat aatcgaagtg cagctgcggc tggcctggcc 780
ccagaaattg ttttgtatac tgagaatgtg gatctggaaa ctccagatac tcatattgta 840
tacaaggcag gcacagatga cagcagctct tctatcaatt tgggtcagca gtccatgccc 900
aacagaccca actacattgg cttcagagac aactttatcg gtctcatgta ctacaacagc 960
actggcaata tgggtgtact ggctggtcag gcctcccagc tgaatgctgt ggtggacttg 1020
caggacagaa acactgaact gtcctaccag ctcttgcttg actctctggg tgacagaacc 1080
aggtatttta gtatgtggaa tcaggcggtg gacagttatg accccgatgt gcgcattatt 1140
gaaaatcacg gtgtggagga tgaactccct aattattgct tcccccttaa tgctgtgggt 1200
agaactgata cttaccaggg aattaaggcc aatggtgctg atcaaaccac atggaccaaa 1260
gatgatactg ttaatgatgc taatgaattg ggcaagggca atcctttcgc catggagatc 1320
aacatccagg ccaacctgtg gcggaacttc ctctacgcga acgtggccct gtacctgccc 1380
gactcctaca agtacacgcc ggccaacatc acgctgccca ccaacaccaa cacctacgat 1440
tacatgaacg gccgcgtggt ggcgccctcg ctggtggacg cctacatcaa catcggggcg 1500
cgctggtcgc tggaccccat ggacaacgtc aaccccttca accaccaccg caacgcgggc 1560
ctgcgctacc gctccatgct cctgggcaac gggcgctacg tgcccttcca catccaggtg 1620
ccccaaaagt tcttcgccat caagagcctc ctgctcctgc ccgggtccta cacctacgag 1680
tggaacttcc gcaaggacgt caacatgatc ctgcagagct ccctcggcaa cgacctgcgc 1740
acggacgggg cctccatcgc cttcaccagc atcaacctct acgccacctt cttccccatg 1800
gcgcacaaca ccgcctccac gctcgaggcc atgctgcgca acgacaccaa cgaccagtcc 1860
ttcaacgact acctctcggc ggccaacatg ctctacccca tcccggccaa tgccaccaac 1920
gtgcccatct ccatcccctc gcgcaactgg gccgccttcc gcggatggtc cttcacgcgc 1980
ctcaagaccc gcgagacgcc ctcgctaggc tccgggttcg acccctactt cgtctactcg 2040
ggctccatcc cctacctcga cggcaccttc tacctcaacc acaccttcaa gaaggtctcc 2100
atcaccttcg actcctccgt cagctggccc ggcaacgacc gcctcctgac gcccaacgag 2160
ttcgaaatca agcgcaccgt cgacggagag gggtacaacg tggcccagtg caacatgacc 2220
aaggactggt tcctggtcca gatgctggcc cactacaaca tcggctacca gggcttctac 2280
gtgcccgagg gctacaagga ccgcatgtac tccttcttcc gcaacttcca gcccatgagc 2340
cgccaggtcg tggacgaggt caactacaag gactaccagg ccgtcaccct ggcctaccag 2400
cacaacaact cgggcttcgt cggctacctc gcgcccacca tgcgccaggg ccagccctac 2460
cccgccaact acccctaccc gctcatcggc aagagcgccg tcgccagcgt cacccagaaa 2520
aagttcctct gcgaccgggt catgtggcgc atccccttct ccagcaactt catgtccatg 2580
ggcgcgctca ccgacctcgg ccagaacatg ctctacgcca actccgccca cgcgctagac 2640
atgaatttcg aagtcgaccc catggatgag tccacccttc tctatgttgt cttcgaagtc 2700
ttcgacgtcg tccgagtgca ccagccccac cgcggcgtca tcgaggccgt ctacctgcgc 2760
acgcccttct cggccggcaa cgccaccacc taa 2793
<210> 22
<211> 2883
<212> DNA
<213> 黑猩猩腺病毒- ChAd 11六邻体
<400> 22
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagtcccgg gctggtgcag ttcgctcgcg ccaccgagag ctacttcagt 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcy 360
tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420
caggcagttg aagaagcagc agaagaggag gaagaagatg ctgacggtca agctgaggaa 480
gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc cggcgaaaaa 540
attagcaaag acggtctgca gataggaacg gacgctacag caaccgaaca aaaacctatt 600
tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcccagtg gaatgaggca 660
gatgctacag tcgctggtgg tagagtgctc aagaaaacca ctcccatgaa accatgctat 720
ggttcctatg caagacccac gaatgctaat ggaggtcagg gtgtactagc ggcaaatgcc 780
caaggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840
aacgaggcta acaacattca gcccaaattg gtgctgtata gcgaggatgt gcacatggag 900
accccggata cacacctctc ttacaagccc acaaaaagcg atgacaattc taaagttatg 960
ctgggccaac aggccatgcc caacaggcct aattacattg gcttcagaga caactttatc 1020
ggtctcatgt actacaacag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080
ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140
gattccatgg gtgacagaac cagatatttc tccatgtgga atcaggcagt ggacagttat 1200
gacccagatg tcagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260
ttccctctgg gcggcatagg ggtaactgac acttaccagg ctgttaagac caacaatggc 1320
aataatgggg gtcaggtgac ttggacaaaa gatgaaactt ttgcagagcg caatgagata 1380
ggggtgggaa acaatttcgc catggagatc aacctcaatg ccaacctgtg gaggaacttc 1440
ctgtactcca acgtggccct gtacctgcca gacaagctta agtacaaccc ctccaacgtg 1500
gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560
ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620
aaccctttca accaccaccg caacgcgggc ctgcgctacc gctccatgct cctgggcaac 1680
gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740
ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800
ctccagagct ctctgggcaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860
atctgcctct acgccacctt cttccccatg gcccacaaca ccgcctccac gctcgaggcc 1920
atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctctccgc cgccaacatg 1980
ctctacccca tccccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040
gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100
tcgggattcg acccctacta cacctactcg ggatccattc cctacctgga cggcaccttc 2160
tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220
ggcaacgacc gcctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggag 2280
ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340
aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400
tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460
gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520
gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctaccc gctcataggc 2580
aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640
atccccttct ccagcaactt catgtccatg ggtgcgctca cggacctggg ccagaacctg 2700
ctctatgcca actccgccca cgcgctcgac atgaccttcg aggtcgaccc catggacgag 2760
cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820
cgcggcgtca tcgagaccgt gtacctgcgc acgcccttct cggccggcaa cgccaccacc 2880
taa 2883
<210> 23
<211> 2835
<212> DNA
<213> 黑猩猩腺病毒- ChAd 16六邻体
<400> 23
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggcccccaa gggagctccc aattccagtc agtgggagca gacggagaac 420
gggggcggac aggctacgac taaaacacac acctatggag ttgccccaat gggtggaact 480
aatattacag tcgacggact acaaattgga actgacgcta cagctgatac ggaaaaacca 540
atttatgctg ataaaacatt ccaacctgag cctcagatag gagaggaaaa ctggcaagaa 600
actgaaagct tttatggcgg tagggctctt aagaaagaca caaacatgaa gccttgttat 660
ggctcatttg ccagacctac caatgaaaag ggaggtcaag ctaaacttaa agttggagct 720
gatgggctgc cgaccaaaga atttgacata gacctagcat tctttgatac tcctggtggc 780
actgtgaccg gaggtacaga ggagtataaa gcagatattg ttatgtatac cgaaaacacg 840
tatctggaaa ctccagacac acatgtggtg tataaaccag gcaaggataa cacaagttct 900
aaaattaacc tggtccagca gtctatgccc aacaggccca actacattgg gtttagggac 960
aactttattg ggctcatgta ttacaacagc actggcaata tgggtgtgct ggccggtcag 1020
gcttctcagt tgaatgctgt ggttgacttg caagacagaa acactgaact gtcttaccag 1080
ctcttgcttg actctttggg tgacagaacc aggtatttca gtatgtggaa tcaggcggtg 1140
gacagttatg atcctgatgt gcgcattatt gaaaaccatg gtgtggaaga tgaacttccc 1200
aactattgct tccccctgga tgggtctggc actaacgccg cttaccaagg tgtgaaagta 1260
aaaaatggtc aagatggtga tgttgagagc gaatgggaaa aagatgatac tgtcgcagct 1320
cgaaatcaat tatgcaaggg caacattttt gccatggaga tcaatctcca ggccaacctg 1380
tggagaagtt ttctctactc gaacgtggcc ctgtacctgc ccgattctta caagtacacg 1440
ccggccaaca tcaccctgcc caccaacacc aacacctacg attacatgaa cgggagagtg 1500
gtgcctccct cgctggtgga cgcctacatc aacatcgggg cgcgctggtc gctggacccc 1560
atggacaacg tcaatccctt caaccaccat cgcaacgcgg ggctgcgcta ccgctccatg 1620
ctcctgggca acgggcgcta cgtgcccttc cacatccagg tgccccagaa atttttcgcc 1680
attaagagcc tcctgctcct gcccgggtcc tacacctacg agtggaactt ccgcaaggac 1740
gtcaacatga tcctgcagag ctccctcggc aacgacctgc gcacggacgg ggcctccatc 1800
tccttcacca gcatcaacct ctacgccacc ttcttcccca tggcgcacaa caccgcctcc 1860
acgctcgagg ccatgctgcg caacgacacc aacgaccagt ccttcaacga ctacctctcg 1920
gcggccaaca tgctctaccc catcccggcc aacgccacca acgtgcccat ctccatcccc 1980
tcgcgcaact gggccgcctt ccgcggctgg tccttcacgc gcctcaagac caaggagacg 2040
ccctcgctgg gctccgggtt cgacccctac ttcgtctact cgggctccat cccctacctc 2100
gacggcacct tctacctcaa ccacaccttc aagaaggtct ccatcacctt cgactcctcc 2160
gtcagctggc ccggcaacga ccggctcctg acgcccaacg agttcgaaat caagcgcacc 2220
gtcgacggcg agggctacaa cgtggcccag tgcaacatga ccaaggactg gttcctggtc 2280
cagatgctgg cccactacaa catcggctac cagggcttct acgtgcccga gggctacaag 2340
gaccgcatgt actccttctt ccgcaacttc cagcccatga gccgccaggt cgtggacgag 2400
gtcaactaca aggactacca ggccgtcacc ctggcctacc agcacaacaa ctcgggcttc 2460
gtcggctacc tcgcgcccac catgcgccag ggccagccct accccgccaa ctacccctac 2520
ccgctcatcg gcaagagcgc cgtcgccagc gtcacccaga aaaagttcct ctgcgaccgg 2580
gtcatgtggc gcatcccctt ctccagcaac ttcatgtcca tgggcgcgct caccgacctc 2640
ggccagaaca tgctctacgc caactccgcc cacgcgctag acatgaattt cgaagtcgac 2700
cccatggatg agtccaccct tctctatgtt gtcttcgaag tcttcgacgt cgtccgagtg 2760
caccagcccc accgcggcgt catcgaggcc gtctacctgc gcaccccctt ctcggccggt 2820
aacgccacca cctaa 2835
<210> 24
<211> 2883
<212> DNA
<213> 黑猩猩腺病毒- ChAd 17六邻体
<400> 24
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcngagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360
tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420
caggcagttg aagaagcagc agaagaggaa gaagaagatg ctgacggtca agctgaggaa 480
gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc tggcgaaaaa 540
attagtaaag atggtctgca aataggaacg gacgctacag ctacagaaca aaaacctatt 600
tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcacagtg gaatgaggca 660
gatgctacag tcgccggcgg tagagtgcta aagaaatcta ctcccatgaa accatgctat 720
ggttcctatg caagacccac aaatgctaat ggaggtcagg gtgtactaac ggcaaatgcc 780
cagggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840
aacgagacta acaacattca gcccaaattg gtgctgtata gtgaggatgt gcacatggag 900
accccggata cgcacctttc ttacaagccc gcaaaaagcg atgacaattc aaaaatcatg 960
ctgggtcagc agtccatgcc caacagacct aattacatcg gcttcagaga taactttatc 1020
ggcctcatgt attacaatag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080
ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140
gattccatgg gtgacagaac cagatacttt tccatgtgga atcaggcagt ggacagttat 1200
gacccagatg ttagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260
ttccctctgg gtggcatagg ggtaactgac acttaccagg ctgttaaaac caacaatggc 1320
aataacgggg gccaggtgac ttggacaaaa gatgaaactt ttgcagatcg caatgaaata 1380
ggggtgggaa acaatttcgc tatggagata aacctcagtg ccaacctgtg gagaaacttc 1440
ctgtactcca acgtggcgct gtacctacca gacaagctta agtacaaccc ctccaatgtg 1500
gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560
ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620
aaccccttca accaccaccg caatgcgggc ctgcgctacc gctccatgct cctgggcaac 1680
gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740
ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800
ctccagagct ctctgggtaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860
atctgcctct acgccacctt cttccccatg gcccacaaca cggcctccac gctcgaggcc 1920
atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctctccgc cgccaacatg 1980
ctctacccca tacccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040
gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100
tcgggattcg acccctacta cacctactcg ggctccattc cctacctgga cggcaccttc 2160
tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220
ggcaacgacc gtctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggag 2280
ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340
aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400
tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460
gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520
gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctatcc gctcataggc 2580
aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640
atccccttct ccagcaactt catgtccatg ggtgcgctct cggacctggg ccagaacttg 2700
ctctacgcca actccgccca cgccctcgac atgaccttcg aggtcgaccc catggacgag 2760
cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820
cgcggcgtca tcgagaccgt gtacctgcgt acgcccttct cggccggcaa cgccaccacc 2880
taa 2883
<210> 25
<211> 2877
<212> DNA
<213> 黑猩猩腺病毒- ChAd 19六邻体
<400> 25
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagt 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcc 360
tacaactccc tggcccccaa gggcgctccc aactcttgtg agtgggagca attagaagaa 420
gcccaggccg ctttggaaga cgaagaatta gaagatgaag acgaggaacc acaggatgag 480
gcgcctgtga aaaagaccca tgtatacgct caggctcccc tttctggaga agaaattact 540
aaagacggtt tgcaaatagg gtcagataac acagaagctc agtctaagcc tatatatgca 600
gaccctacat tccagcccga accccaaatc ggggagtccc agtggaacga ggcagatgct 660
acagtcgctg gtggtagagt gctcaagaaa accactccca tgaaaccatg ctatggttcc 720
tatgcaagac ccacgaatgc taatggaggt cagggtgtgc tggtggctga tgataagggg 780
gtccttcaat ctaaagttga attgcaattt ttttcaaata ctactactct taatcagcgg 840
gagggtaatg atacaaaacc aaaagtagtg ctgtatagcg aggatgtgca catggaaaca 900
ccagacaccc acatttctta caagcccaca aaaagcgatg acaattctaa agttatgctg 960
ggccaacagt ccatgcccaa caggcctaat tacatcggct tcagagacaa ctttatcggt 1020
ctcatgtact acaacagcac tggcaacatg ggagtgcttg caggtcaggc ctctcagttg 1080
aatgcagtgg tggacttgca agacagaaac acagaactgt cctaccagct cttgcttgat 1140
tccatgggtg acagaaccag atatttctcc atgtggaatc aggcagtgga cagttatgac 1200
ccggatgtca gaattattga aaatcatgga accgaagacg agctccccaa ctattgtttt 1260
cctctgggtg gcataggggt aactgacact taccaggtca ttaaaactaa tggcaatggt 1320
caagcagacc caacctggga aaaagataca gagtttgcag accgcaatga aataggggtg 1380
ggaaacaatt tcgccatgga gatcaacctc aatgccaacc tgtggaggaa cttcctgtac 1440
tccaacgtgg ccctgtacct gccagacaag cttaagtaca acccctccaa cgtggacatc 1500
tctgacaacc ccaacaccta cgattacatg aacaagcgag tggtggcccc ggggctggtg 1560
gactgctaca tcaacctggg cgcgcgctgg tcgctggact acatggacaa cgtcaacccc 1620
ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680
tacgtgccct tccacatcca ggtgccccag aagttctttg ccatcaagaa cctcctcctc 1740
ctgccgggct cctacaccta cgagtggaac ttcaggaagg atgtcaacat ggtcctccag 1800
agctctttgg gcaacgatct cagggtggac ggggccagca tcaagttcga gagcatctgc 1860
ctctacgcca ccttcttccc catggcccac aacaccgcct ccacgctcga ggccatgctc 1920
aggaacgaca ccaacgacca gtccttcaat gactacctct ccgccgccaa catgctctac 1980
cccatccccg ccaacgccac caacgtccct atctccatcc cctcgcgcaa ctgggcggcc 2040
ttccgcggct gggccttcac ccgcctcaag accaaggaga caccctccct gggctcggga 2100
ttcgacccct actacaccta ctcgggatcc attccctacc tggacggcac cttctacctc 2160
aaccacactt tcaagaaggt ctcggtcacc ttcgactcct cggtcagctg gccgggcaac 2220
gaccgcctgc tcacccccaa cgagttcgag atcaagcgct cggtcgacgg ggagggctac 2280
aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggccaactac 2340
aacatcggct accagggctt ctacatccca gagagctaca aggacaggat gtactccttc 2400
ttcaggaact tccagcccat gagccggcag gtggtggacc aaaccaagta caaggactac 2460
caggaggtgg gcatcatcca ccagcacaac aactcgggct tcgtgggcta cctcgccccc 2520
accatgcgcg agggacaggc ctaccccgcc aacttcccct acccgctcat aggcaagacc 2580
gcggtcgaca gcatcaccca gaaaaagttc ctctgcgacc gcaccctctg gcgcatcccc 2640
ttctccagca acttcatgtc catgggtgcg ctcacggacc tgggccagaa cctgctctat 2700
gccaactccg cccacgcgct cgacatgacc ttcgaggtcg accccatgga cgagcccacc 2760
cttctctatg ttctgttcga agtctttgac gtggtccggg tccaccagcc gcaccgcggc 2820
gtcatcgaga ccgtgtacct gcgcacgccc ttctcggccg gcaacgccac cacctaa 2877
<210> 26
<211> 49
<212> DNA
<213> 人工序列
<220>
<223> polA
<400> 26
aataaaagat ctttattttc attagatctg tgtgttggtt ttttgtgtg 49
<210> 27
<211> 37
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 27
atggaattcg tttaaaccat catcaataat atacctc 37
<210> 28
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 28
cgctggcact caagagtggc ctc 23
<210> 29
<211> 37
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 29
atgaagcttg tttaaaccca tcatcaataa tatacct 37
<210> 30
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 30
atctagacag cgtccatagc ttaccg 26
<210> 31
<211> 44
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 31
atgctacgta gcgatcgcgt gagtagtgtt tgggggtggg tggg 44
<210> 32
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 32
taggcgcgcc gcttctcctc gttcaggctg gcg 33
<210> 33
<211> 38
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 33
gatctagtta gtttaaacga attcggatct gcgacgcg 38
<210> 34
<211> 37
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 34
ttcgatcatg tttaaacgaa attaagaatt cggatcc 37
<210> 35
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 35
tattctgcga tcgctgaggt gggtgagtgg gcg 33
<210> 36
<211> 31
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 36
taggcgcgcc cttaaacggc atttgtggga g 31
<210> 37
<211> 27
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 37
cgtctagaag acccgagtct taccagt 27
<210> 38
<211> 39
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 38
cgggatccgt ttaaaccatc atcaataata taccttatt 39
<210> 39
<211> 37
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 39
atggaattcg tttaaaccat catcaataat atacctt 37
<210> 40
<211> 45
<212> DNA
<213> 人工序列
<220>
<223> 寡聚物
<400> 40
atgacgcgat cgctgatatc ctataataat aaaacgcaga ctttg 45
<210> 41
<211> 2880
<212> DNA
<213> 黑猩猩腺病毒- ChAd 3六邻体
<400> 41
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggggtgct ggaccggggt cccactttca agccctactc tggcaccgcc 360
tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca agaggaaact 420
caggcagttg aagaagcagc agaagaggaa gaagaagatg ctgacggtca agctgaggaa 480
gagcaagcag ctaccaaaaa gactcatgta tatgctcagg ctcccctttc tggcgaaaaa 540
attagtaaag atggtctgca aataggaacg gacgctacag ctacagaaca aaaacctatt 600
tatgcagacc ctacattcca gcccgaaccc caaatcgggg agtcccagtg gaatgaggca 660
gatgctacag tcgccggcgg tagagtgcta aagaaatcta ctcccatgaa accatgctat 720
ggttcctatg caagacccac aaatgctaat ggaggtcagg gtgtactaac ggcaaatgcc 780
cagggacagc tagaatctca ggttgaaatg caattctttt caacttctga aaacgcccgt 840
aacgaggcta acaacattca gcccaaattg gtgctgtata gtgaggatgt gcacatggag 900
accccggata cgcacctttc ttacaagccc gcaaaaagcg atgacaattc aaaaatcatg 960
ctgggtcagc agtccatgcc caacagacct aattacatcg gcttcagaga caactttatc 1020
ggcctcatgt attacaatag cactggcaac atgggagtgc ttgcaggtca ggcctctcag 1080
ttgaatgcag tggtggactt gcaagacaga aacacagaac tgtcctacca gctcttgctt 1140
gattccatgg gtgacagaac cagatacttt tccatgtgga atcaggcagt ggacagttat 1200
gacccagatg ttagaattat tgaaaatcat ggaactgaag acgagctccc caactattgt 1260
ttccctctgg gtggcatagg ggtaactgac acttaccagg ctgttaaaac caacaatggc 1320
aataacgggg gccaggtgac ttggacaaaa gatgaaactt ttgcagatcg caatgaaata 1380
ggggtgggaa acaatttcgc tatggagatc aacctcagtg ccaacctgtg gagaaacttc 1440
ctgtactcca acgtggcgct gtacctacca gacaagctta agtacaaccc ctccaatgtg 1500
gacatctctg acaaccccaa cacctacgat tacatgaaca agcgagtggt ggccccgggg 1560
ctggtggact gctacatcaa cctgggcgcg cgctggtcgc tggactacat ggacaacgtc 1620
aaccccttca accaccaccg caatgcgggc ctgcgctacc gctccatgct cctgggcaac 1680
gggcgctacg tgcccttcca catccaggtg ccccagaagt tctttgccat caagaacctc 1740
ctcctcctgc cgggctccta cacctacgag tggaacttca ggaaggatgt caacatggtc 1800
ctccagagct ctctgggtaa cgatctcagg gtggacgggg ccagcatcaa gttcgagagc 1860
atctgcctct acgccacctt cttccccatg gcccacaaca cggcctccac gctcgaggcc 1920
atgctcagga acgacaccaa cgaccagtcc ttcaatgact acctttccgc cgccaacatg 1980
ctctacccca tacccgccaa cgccaccaac gtccccatct ccatcccctc gcgcaactgg 2040
gcggccttcc gcggctgggc cttcacccgc ctcaagacca aggagacccc ctccctgggc 2100
tcgggattcg acccctacta cacctactcg ggctctattc cctacctgga cggcaccttc 2160
tacctcaacc acactttcaa gaaggtctcg gtcaccttcg actcctcggt cagctggccg 2220
ggcaacgacc gtctgctcac ccccaacgag ttcgagatca agcgctcggt cgacggggaa 2280
ggctacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca gatgctggcc 2340
aactacaaca tcggctacca gggcttctac atcccagaga gctacaagga caggatgtac 2400
tccttcttca ggaacttcca gcccatgagc cggcaggtgg tggaccagac caagtacaag 2460
gactaccagg aggtgggcat catccaccag cacaacaact cgggcttcgt gggctacctc 2520
gcccccacca tgcgcgaggg acaggcctac cccgccaact tcccctaccc gctcataggc 2580
aagaccgcgg tcgacagcat cacccagaaa aagttcctct gcgaccgcac cctctggcgc 2640
atccccttct ccagcaactt catgtccatg ggtgcgctct cggacctggg ccagaacttg 2700
ctctacgcca actccgccca cgccctcgac atgaccttcg aggtcgaccc catggacgag 2760
cccacccttc tctatgttct gttcgaagtc tttgacgtgg tccgggtcca ccagccgcac 2820
cgcggcgtca tcgagaccgt gtacctgcgt acgcccttct cggccggcaa cgccaccacc 2880
<210> 42
<211> 1683
<212> DNA
<213> 黑猩猩腺病毒- ChAd 3纤维
<400> 42
atgtcagatt cttgctcctg tccctccgca cccactatct tcatgttgtt gcagatgaag 60
cgcaccaaaa cgtctgacga gagcttcaac cccgtgtacc cctatgacac ggaaagcggc 120
cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagaaagc 180
ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc 240
gccctgaaaa tgggaagtgg cctctccctg gacgacgctg gcaacctcac ctctcaagat 300
atcaccaccg ctagccctcc cctcaaaaaa accaagacca acctcagcct agaaacctca 360
tcccccctaa ctgtaagcac ctcaggcgcc ctcaccgtag cagccgccgc tcccctggca 420
gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa 480
ctcaccctgg ccaccaaagg ccccctgacc gtgtctgaag gcaaactggc cttgcaaaca 540
tcggccccgc tgacggccgc tgacagcagc accctcaccg ttagcgccac accaccaatt 600
aatgtaagca gtggaagttt aggcttagac atggaagacc ctatgtatac tcacgatgga 660
aaactgggaa taagaattgg gggtccacta agagtagtag acagcttgca cacactcact 720
gtagttaccg gaaatggact aactgtagat aacaatgccc tccaaactag agttacgggc 780
gccctaggtt atgacacatc aggaaatcta caattgagag ctgcaggagg tatgcgaatt 840
gatgcaaatg gccaacttat ccttaatgtg gcatacccat ttgatgctca gaacaatctc 900
agccttagac ttggtcaggg acccctgtat ataaacacag accacaacct ggatttgaat 960
tgcaacagag gtctaaccac aactaccacc aacaacacaa aaaaacttga gactaaaatt 1020
agctcaggct tagactatga caccaatggt gctgtcatta ttaaacttgg cactggtcta 1080
agcttcgaca acacaggcgc cctaactgtg ggaaacactg gtgatgataa actgactctg 1140
tggacgaccc cagacccatc tccaaattgc agaattcact cagacaaaga ctgcaagttt 1200
actctagtcc taactaagtg tggaagccaa atcctggcct ctgtcgccgc cctagcggta 1260
tcaggaaatc tggcttcgat aacaggcacc gttgccagcg ttaccatctt tctcagattt 1320
gatcagaatg gagtgcttat ggaaaactcc tcgctagaca ggcagtactg gaacttcaga 1380
aatggcaact caactaacgc tgccccctac accaatgcag ttgggttcat gccaaacctc 1440
gcagcatacc ccaaaacgca aagccagact gctaaaaaca acattgtaag tcaggtttac 1500
ttgaatggag acaaatccaa acccatgacc cttaccatca ccctcaatgg aactaatgaa 1560
tccagtgaaa ctagccaggt gagtcactac tccatgtcat ttacatgggc ttgggaaagt 1620
gggcaatatg ccactgaaac ctttgccacc aactccttca ccttttctta cattgctgaa 1680
caa 1683
<210> 43
<211> 2859
<212> DNA
<213> 黑猩猩腺病毒- ChAd 6六邻体
<400> 43
atgtatgtcc gccgaccaga aggaagaggc gcgtcgccga gttgcaagat ggccacccca 60
tcgatgctgc cccagtgggc gtacatgcac atcgccggac aggacgcttc ggagtacctg 120
agtccgggtc tggtgcagtt cgcccgcgcc acagacacct acttcagtct ggggaacaag 180
tttaggaacc ccacggtggc gcccacgcac gatgtgacca ccgaccgcag ccagcggctg 240
acgctgcgct tcgtgcccgt ggaccgcgag gacaacacct actcgtacaa agtgcgctac 300
acgctggccg tgggcgacaa ccgcgtgctg gacatggcca gcacctactt tgacatccgc 360
ggcgtgctgg atcggggccc cagcttcaaa ccctactccg gcaccgccta caacagcctg 420
gctcccaagg gagcgcccaa cacctcacag tggataacca aagacaatgg aactgataag 480
acatacagtt ttggaaatgc tccagtcaga ggattggaca ttacagaaga gggtctccaa 540
ataggacccg atgagtcagg gggtgaaagc aagaaaattt ttgcagacaa aacctatcag 600
cctgaacctc agcttggaga tgaggaatgg catgatacta ttggagctga agacaagtat 660
ggaggcagag cgcttaaacc tgccaccaac atgaaaccct gctatgggtc tttcgccaag 720
ccaactaatg ctaagggagg tcaggctaaa agcagaacca aggacgatgg cactactgag 780
cctgatattg acatggcctt ctttgacgat cgcagtcagc aagctagttt cagtccagaa 840
cttgttttgt atactgagaa tgtcgatctg gacaccccgg atacccacat tatttacaaa 900
cctggcactg atgaaacaag ttcttctttc aacttgggtc agcagtccat gcccaacaga 960
cccaactaca tcggcttcag agacaacttt atcggtctca tgtactacaa cagtactggc 1020
aatatgggtg tactagctgg acaggcctcc cagctgaatg ctgtggtgga cttgcaggac 1080
agaaacactg aactgtccta ccagctcttg cttgactctc tgggtgacag aaccaggtat 1140
ttcagtatgt ggaaccaggc ggtggacagc tacgaccccg atgtgcgcat tattgaaaat 1200
cacggtgtgg aggatgaact acccaactat tgcttccctt tgaatggtgt gggctttaca 1260
gatacattcc agggaattaa ggttaaaact accaataacg gaacagcaaa tgctacagag 1320
tgggaatctg atacctctgt caataatgct aatgagattg ccaagggcaa tcctttcgcc 1380
atggagatca acatccaggc caacctgtgg cggaacttcc tctacgcgaa cgtggcgctg 1440
tacctgcccg actcctacaa gtacacgccg gccaacatca cgctgcccgc caacaccaac 1500
acctacgatt acatgaacgg ccgcgtggta gcgccctcgc tggtggacgc ctacatcaac 1560
atcggggcgc gctggtcgct ggaccccatg gacaacgtca accccttcaa ccaccaccgc 1620
aacgcgggcc tgcgctaccg ctccatgctc ctgggcaacg ggcgctacgt gcccttccac 1680
atccaggtgc cccaaaagtt tttcgccatc aagagcctcc tgctcctgcc cgggtcctac 1740
acctacgagt ggaacttccg caaggacgtc aacatgatcc tgcagagctc cctcggcaac 1800
gacctgcgca cggacggggc ctccatcgcc ttcaccagca tcaacctcta cgccaccttc 1860
ttccccatgg cgcacaacac cgcctccacg ctcgaggcca tgctgcgcaa cgacaccaac 1920
gaccagtcct tcaacgacta cctctcggcg gccaacatgc tctaccccat cccggccaac 1980
gccaccaacg tgcccatctc catcccctcg cgcaactggg ccgccttccg cggctggtcc 2040
ttcacgcgcc tcaagacccg cgagacgccc tcgctcggct ccgggttcga cccctacttc 2100
gtctactcgg gctccatccc ctacctcgac ggcaccttct acctcaacca caccttcaag 2160
aaggtctcca tcaccttcga ctcctccgtc agctggcccg gcaacgaccg cctcctgacg 2220
cccaacgagt tcgaaatcaa gcgcaccgtc gacggagagg ggtacaacgt ggcccagtgc 2280
aacatgacca aggactggtt cctggttcag atgctggccc actacaacat cggctaccag 2340
ggcttctacg tgcccgaggg ctacaaggac cgcatgtact ccttcttccg caacttccag 2400
cccatgagcc gccaggtcgt ggacgaggtc aactacaagg actaccaggc cgtcaccctg 2460
gcctaccagc acaacaactc gggcttcgtc ggctacctcg cgcccaccat gcgccaggga 2520
cagccctacc ccgccaacta cccctacccg ctcatcggca agagcgccgt cgccagcgtc 2580
acccagaaaa agttcctctg cgaccgggtc atgtggcgca tccccttctc cagcaacttc 2640
atgtccatgg gcgcgctcac cgacctcggc cagaacatgc tctacgccaa ctccgcccac 2700
gcgctagaca tgaatttcga agtcgacccc atggatgagt ccacccttct ctatgttgtc 2760
ttcgaagtct tcgacgtcgt ccgagtgcac cagccccacc gcggcgtcat cgaggccgtc 2820
tacctgcgca cgcccttctc ggccggtaac gccaccacc 2859
<210> 44
<211> 1335
<212> DNA
<213> 黑猩猩腺病毒- ChAd 6纤维
<400> 44
atgtccaaaa agcgcgcgcg ggtggatgat gacttcgacc ccgtgtaccc ctacgatgca 60
gacaacgcac cgactgtgcc cttcatcaac cctcccttcg tctcttcaga tggattccaa 120
gaaaagcccc tgggggtgtt gtccctgcga ctggccgatc ccgtcaccac caagaacggg 180
gctgtcaccc tcaagctggg ggagggggtg gacctcgacg actcgggaaa actcatctcc 240
aaaaatgcca ccaaggccac tgcccctctc agtatttcca acaacaccat ttcccttaac 300
atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360
aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420
acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480
agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540
attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600
agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660
aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720
caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780
aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840
tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcagatactg 900
ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggaaaagta 960
accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaagc cagttcaaca 1020
ctagataaag aatattggaa tttcagaaaa ggagatgtga cacctgctga cccctacact 1080
aatgctatag gctttatgcc caaccttaat gcatacccaa aaaacacaaa cgcagctgca 1140
aaaagtcaca ttgttggaaa agtataccta catggggatg aaagcaagcc actagacttg 1200
ataattacat ttaatgaaac cagtgatgaa tcctgtactt attgcattaa ctttcagtgg 1260
cagtggggaa ctgaccaata taaagatgaa acacttgcag tcagttcatt caccttctca 1320
tacattgcta aagaa 1335
<210> 45
<211> 22
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 45
tgtcctacca rctcttgctt ga 22
<210> 46
<211> 18
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 46
gtggaarggc acgtagcg 18
<210> 47
<211> 9
<212> PRT
<213> HIV gag CD8表位
<220>
<223> 引物
<400> 47
Ala Met Gln Met Leu Lys Glu Thr Ile
1 5
<210> 48
<211> 578
<212> PRT
<213> 黑猩猩腺病毒- ChAd 20纤维
<400> 48
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp
180 185 190
Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe
195 200 205
Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val
210 215 220
Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val
225 230 235 240
Ser Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn
290 295 300
Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val
305 310 315 320
Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala
325 330 335
Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp Ser Gly Ser Asp Thr Asn
340 345 350
Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Asp Tyr Asp Ser Ser Arg
355 360 365
Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly
370 375 380
Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr
385 390 395 400
Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala
405 410 415
Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser
420 425 430
Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr
435 440 445
Val Thr Ser Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly Val Leu
450 455 460
Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly
465 470 475 480
Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro
485 490 495
Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn
500 505 510
Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr
515 520 525
Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val
530 535 540
Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr
545 550 555 560
Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala
565 570 575
Gln Glu
<210> 49
<211> 425
<212> PRT
<213> 黑猩猩腺病毒- ChAd 4纤维
<400> 49
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu
115 120 125
Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser
130 135 140
Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly
145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp
165 170 175
Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp
180 185 190
Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser
195 200 205
Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu
210 215 220
Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn
225 230 235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
245 250 255
Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu
260 265 270
Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val
275 280 285
Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300
Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser
305 310 315 320
Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly
325 330 335
Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350
Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val
355 360 365
Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu
370 375 380
Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400
Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser
405 410 415
Tyr Thr Phe Ser Tyr Ile Ala Gln Glu
420 425
<210> 50
<211> 444
<212> PRT
<213> 黑猩猩腺病毒- ChAd 5纤维
<400> 50
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Asp Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln
210 215 220
Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Ser Leu
225 230 235 240
Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Leu Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Arg
305 310 315 320
Thr Ala Leu Val Ser Leu Lys Phe Asn Ala Asn Gly Ala Leu Leu Asp
325 330 335
Lys Ser Thr Leu Asn Lys Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu
340 345 350
Ile Pro Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys
355 360 365
Lys Ala Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val
370 375 380
Gly Asp Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile
385 390 395 400
Ile Thr Phe Asn Glu Thr Asp Asp Glu Thr Cys Asp Tyr Cys Ile Asn
405 410 415
Phe Gln Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala
420 425 430
Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 51
<211> 445
<212> PRT
<213> 黑猩猩腺病毒- ChAd 7纤维
<400> 51
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Thr
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Ala Pro Leu Ala Phe Asp Ser Asn
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Asn Arg Gly Leu Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Thr Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Met Gly Val Asn Ile Asp Thr Gln Lys Gly Leu Gln
210 215 220
Phe Gly Thr Thr Ser Thr Val Ala Asp Val Lys Asn Ala Tyr Pro Ile
225 230 235 240
Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Asp Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Gln Val
305 310 315 320
Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln
325 330 335
Thr Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp
340 345 350
Val Thr Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn
355 360 365
Leu Lys Ala Tyr Pro Lys Asn Thr Ser Gly Ala Ala Lys Ser His Ile
370 375 380
Val Gly Lys Val Tyr Leu His Gly Asp Thr Asp Lys Pro Leu Asp Leu
385 390 395 400
Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile
405 410 415
Asn Phe Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Glu Thr Leu
420 425 430
Ala Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440 445
<210> 52
<211> 425
<212> PRT
<213> 黑猩猩腺病毒- ChAd 9纤维
<400> 52
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ala Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu
115 120 125
Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser
130 135 140
Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly
145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp
165 170 175
Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp
180 185 190
Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser
195 200 205
Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu
210 215 220
Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn
225 230 235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
245 250 255
Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu
260 265 270
Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val
275 280 285
Gly Ser Gly Asp Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300
Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser
305 310 315 320
Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly
325 330 335
Thr Pro Tyr Ala Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350
Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val
355 360 365
Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu
370 375 380
Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400
Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser
405 410 415
Tyr Thr Phe Ser Tyr Ile Ala Gln Glu
420 425
<210> 53
<211> 425
<212> PRT
<213> 黑猩猩腺病毒- ChAd 10纤维
<400> 53
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu
115 120 125
Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser
130 135 140
Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly
145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp
165 170 175
Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp
180 185 190
Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser
195 200 205
Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu
210 215 220
Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn
225 230 235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
245 250 255
Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu
260 265 270
Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val
275 280 285
Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300
Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser
305 310 315 320
Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly
325 330 335
Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350
Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val
355 360 365
Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu
370 375 380
Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400
Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser
405 410 415
Tyr Thr Phe Ser Tyr Ile Ala Gln Glu
420 425
<210> 54
<211> 578
<212> PRT
<213> 黑猩猩腺病毒- ChAd 11纤维
<400> 54
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Leu Ala Ala Ala Val Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Ile
165 170 175
Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp
180 185 190
Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe
195 200 205
Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val
210 215 220
Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val
225 230 235 240
Ser Gly Ala Leu Asn Tyr Asp Ser Ser Gly Asn Leu Glu Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Val Asp Ala Asn Gly Lys Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn
290 295 300
Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val
305 310 315 320
Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala
325 330 335
Ile Asn Pro Gly Asp Gly Leu Glu Phe Gly Ser Gly Ser Asp Thr Asn
340 345 350
Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Glu Tyr Asp Ser Ser Arg
355 360 365
Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly
370 375 380
Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr
385 390 395 400
Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala
405 410 415
Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser
420 425 430
Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr
435 440 445
Val Thr Ser Ala Gln Ile Ile Leu Arg Phe Asp Glu Asn Gly Val Leu
450 455 460
Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly
465 470 475 480
Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro
485 490 495
Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn
500 505 510
Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Ile
515 520 525
Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val
530 535 540
Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr
545 550 555 560
Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala
565 570 575
Gln Glu
<210> 55
<211> 442
<212> PRT
<213> 黑猩猩腺病毒- ChAd 16纤维
<400> 55
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Thr Met Gln Val Thr Ala Pro Leu Lys Leu Ala Asn Thr Ala Ile Leu
115 120 125
Asn Thr Leu Ala Met Ala Tyr Gly Asn Gly Leu Gly Leu Ser Asn Asn
130 135 140
Ala Leu Thr Val Gln Leu Gln Ser Pro Leu Thr Phe Asn Asn Ser Lys
145 150 155 160
Val Ala Ile Asn Leu Gly Asn Gly Pro Leu Asn Val Thr Ser Asn Arg
165 170 175
Leu Ser Ile Asn Cys Lys Arg Gly Val Tyr Val Thr Thr Thr Gly Asp
180 185 190
Ala Ile Glu Thr Asn Ile Ser Trp Ser Asn Ala Ile Lys Phe Ile Gly
195 200 205
Asn Ala Met Gly Val Asn Ile Asp Thr Asn Lys Gly Leu Gln Phe Gly
210 215 220
Thr Thr Ser Thr Val Thr Asp Val Thr Asn Ala Phe Pro Ile Gln Val
225 230 235 240
Lys Leu Gly Ala Gly Leu Ala Phe Asp Ser Thr Gly Ala Ile Val Ala
245 250 255
Trp Asn Lys Glu Asp Asp Ser Leu Thr Leu Trp Thr Thr Pro Asp Pro
260 265 270
Ser Pro Asn Cys Lys Ile Ala Ser Asp Lys Asp Ala Lys Leu Thr Leu
275 280 285
Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser Leu Leu
290 295 300
Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Ser Thr Ala
305 310 315 320
Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Ala Leu Leu Glu Lys Ser
325 330 335
Thr Leu Asn Arg Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu Ile Pro
340 345 350
Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys Lys Ala
355 360 365
Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val Gly Glu
370 375 380
Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile Ile Thr
385 390 395 400
Phe Asn Glu Thr Asp Asp Glu Ser Cys Asp Tyr Cys Met Asn Phe Gln
405 410 415
Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala Thr Ser
420 425 430
Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 56
<211> 543
<212> PRT
<213> 黑猩猩腺病毒- ChAd 17纤维
<400> 56
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Ile Thr Ser Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Ala Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ser Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp
180 185 190
Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
195 200 205
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220
Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr Arg Val
225 230 235 240
Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300
Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr
305 310 315 320
Lys Ile Ser Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335
Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Leu Thr Val
340 345 350
Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro
355 360 365
Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu
370 375 380
Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu
385 390 395 400
Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val
405 410 415
Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser
420 425 430
Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
435 440 445
Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala
450 455 460
Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln
465 470 475 480
Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr
485 490 495
Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr
500 505 510
Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu
515 520 525
Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln
530 535 540
<210> 57
<211> 543
<212> PRT
<213> 黑猩猩腺病毒- ChAd 19纤维
<400> 57
Met Lys Arg Thr Lys Thr Ser Asp Lys Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Leu Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ala Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp
180 185 190
Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
195 200 205
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220
Thr Gly Asn Gly Ile Ala Val Asp Asn Asn Ala Leu Gln Thr Arg Val
225 230 235 240
Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300
Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr
305 310 315 320
Lys Ile Gly Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335
Lys Leu Gly Thr Gly Val Ser Phe Asp Ser Thr Gly Ala Leu Ser Val
340 345 350
Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro
355 360 365
Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu
370 375 380
Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu
385 390 395 400
Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ser Ser Val
405 410 415
Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser
420 425 430
Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
435 440 445
Ala Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala
450 455 460
Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln
465 470 475 480
Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr
485 490 495
Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr
500 505 510
Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu
515 520 525
Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln
530 535 540
<210> 58
<211> 963
<212> DNA
<213> 黑猩猩腺病毒- ChAd 8纤维
<400> 58
atgaccaaac gagttcgact aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60
agcagctccc aacacccctt tataaaccct ggtttcattt cctcaaatgg atttacacaa 120
agcccagatg gggttcttac acttaaatgc ttatcgccgc tcaccaccac aggcggctcc 180
cttcaactta aagttggagg aggattatca gtggatgaca ctgacggttc attagaagaa 240
aacataagca ttacagcacc acttaataaa acaagtcact caataggttt atccatagga 300
gatgggttgg aaacaaaaaa caaccaacta tgtgctaagc tgggagacgg tcttacattt 360
aatacaggca gcatatgcat agatactgac attaatacat tatggacagg agcaacacca 420
gacgctaatt gcttagtcct tggaactgaa tctaatgatt gtaaacttac actggcactt 480
gtaaagtcag gagccttagt aaatgcttac gtagcacttg ttggagcctc agacgccgtt 540
aatgatttaa ccacagaaac aagtgctcaa ataattgcag acatatattt tgatgcgcaa 600
ggaaaacttc ttcctgattt atcagcactc aaaacagagc taaaacacaa atctggacaa 660
ggcacttcga cagcagatcc caataactgt aaaagcttta tgccaagtct aaatgcatat 720
ccactgcgcc ccaatggagg caacggaaac tatatttatg gaaccaccta ctacagggcc 780
agagatgaaa ccctttatga acttaaaacc tctgtaatgc ttaactacaa aattaccagt 840
ggactatgtg catatgccat gcattttcag tggtcttgga atagtgggac taaaccagaa 900
gacactcccg ccactttcat tgcctccccc tttgtctttt cctacattag agaagatgac 960
tga 963
<210> 59
<211> 320
<212> PRT
<213> 黑猩猩腺病毒- ChAd 8纤维
<400> 59
Met Thr Lys Arg Val Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe
20 25 30
Ile Ser Ser Asn Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu
35 40 45
Lys Cys Leu Ser Pro Leu Thr Thr Thr Gly Gly Ser Leu Gln Leu Lys
50 55 60
Val Gly Gly Gly Leu Ser Val Asp Asp Thr Asp Gly Ser Leu Glu Glu
65 70 75 80
Asn Ile Ser Ile Thr Ala Pro Leu Asn Lys Thr Ser His Ser Ile Gly
85 90 95
Leu Ser Ile Gly Asp Gly Leu Glu Thr Lys Asn Asn Gln Leu Cys Ala
100 105 110
Lys Leu Gly Asp Gly Leu Thr Phe Asn Thr Gly Ser Ile Cys Ile Asp
115 120 125
Thr Asp Ile Asn Thr Leu Trp Thr Gly Ala Thr Pro Asp Ala Asn Cys
130 135 140
Leu Val Leu Gly Thr Glu Ser Asn Asp Cys Lys Leu Thr Leu Ala Leu
145 150 155 160
Val Lys Ser Gly Ala Leu Val Asn Ala Tyr Val Ala Leu Val Gly Ala
165 170 175
Ser Asp Ala Val Asn Asp Leu Thr Thr Glu Thr Ser Ala Gln Ile Ile
180 185 190
Ala Asp Ile Tyr Phe Asp Ala Gln Gly Lys Leu Leu Pro Asp Leu Ser
195 200 205
Ala Leu Lys Thr Glu Leu Lys His Lys Ser Gly Gln Gly Thr Ser Thr
210 215 220
Ala Asp Pro Asn Asn Cys Lys Ser Phe Met Pro Ser Leu Asn Ala Tyr
225 230 235 240
Pro Leu Arg Pro Asn Gly Gly Asn Gly Asn Tyr Ile Tyr Gly Thr Thr
245 250 255
Tyr Tyr Arg Ala Arg Asp Glu Thr Leu Tyr Glu Leu Lys Thr Ser Val
260 265 270
Met Leu Asn Tyr Lys Ile Thr Ser Gly Leu Cys Ala Tyr Ala Met His
275 280 285
Phe Gln Trp Ser Trp Asn Ser Gly Thr Lys Pro Glu Asp Thr Pro Ala
290 295 300
Thr Phe Ile Ala Ser Pro Phe Val Phe Ser Tyr Ile Arg Glu Asp Asp
305 310 315 320
<210> 60
<211> 1062
<212> DNA
<213> 黑猩猩腺病毒- ChAd 22纤维
<400> 60
atggccaaac gagctcggct aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60
agcagctcac aacacccctt tataaaccct ggtttcattt cctcaaatgg ttttgcacaa 120
agcccagatg gagttctaac tcttaaatgt gttaatccgc tcactaccgc cagcggaccc 180
ctccaactta aagttggaag cagtcttaca gtagataata tcgatgggtc tttggaggaa 240
aatataactg ccgcagcgcc actcactaaa actaaccact ccataggttt atcaatagga 300
tctggcttgc aaacaaagga tgataaactt tgtttatcgc tgggagatgg gttggtaaca 360
aaggatgata aactatgttt atcgctggga gatgggttaa taacaaaaga tgatacacta 420
tgtgccaaac taggacatgg ccttgtgttt gactcttcca atgctatcac catagaaaac 480
aacaccttgt ggacaggtgc aaaaccaagc gccaactgtg taattaaaga gggagaagat 540
tccccagact gtaagctcac tttagttcta gtgaagaatg gaggactgat aaatggatac 600
ataacattaa tgggagcctc agaatatact aacaccttgt ttaaaaacaa acaagttaca 660
atcgatgtaa acctcgcatt tgataatact ggccaaatta tcacttacct atcatccctt 720
aaaagtaacc tgaactttaa agacaaccaa aacatggcta ctggaaccat aaccagtgcc 780
aaaggcttca tgcccagcac caccgcctat ccatttataa catacgccac tcagtcccta 840
aatgaagatt acatttatgg agagtgttac tacaaatcta ccaatggaac tctctttcca 900
ctaaaagtta ctgtcacact aaacagacgt atgtcagctt ctggaatggc ctatgctatg 960
aatttttcat ggtctctaaa tgcagaggaa gccccggaaa ctaccgaagt cactctcatt 1020
acctccccct tctttttttc ttatatcaga gaagatgact ga 1062
<210> 61
<211> 353
<212> PRT
<213> 黑猩猩腺病毒- ChAd 22纤维
<400> 61
Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe
20 25 30
Ile Ser Ser Asn Gly Phe Ala Gln Ser Pro Asp Gly Val Leu Thr Leu
35 40 45
Lys Cys Val Asn Pro Leu Thr Thr Ala Ser Gly Pro Leu Gln Leu Lys
50 55 60
Val Gly Ser Ser Leu Thr Val Asp Asn Ile Asp Gly Ser Leu Glu Glu
65 70 75 80
Asn Ile Thr Ala Ala Ala Pro Leu Thr Lys Thr Asn His Ser Ile Gly
85 90 95
Leu Ser Ile Gly Ser Gly Leu Gln Thr Lys Asp Asp Lys Leu Cys Leu
100 105 110
Ser Leu Gly Asp Gly Leu Val Thr Lys Asp Asp Lys Leu Cys Leu Ser
115 120 125
Leu Gly Asp Gly Leu Ile Thr Lys Asp Asp Thr Leu Cys Ala Lys Leu
130 135 140
Gly His Gly Leu Val Phe Asp Ser Ser Asn Ala Ile Thr Ile Glu Asn
145 150 155 160
Asn Thr Leu Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile Lys
165 170 175
Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val Lys
180 185 190
Asn Gly Gly Leu Ile Asn Gly Tyr Ile Thr Leu Met Gly Ala Ser Glu
195 200 205
Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val Asn
210 215 220
Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser Leu
225 230 235 240
Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly Thr
245 250 255
Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro Phe
260 265 270
Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly Glu
275 280 285
Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val Thr
290 295 300
Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala Met
305 310 315 320
Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr Glu
325 330 335
Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu Asp
340 345 350
Asp
<210> 62
<211> 1686
<212> DNA
<213> 黑猩猩腺病毒- ChAd 24纤维
<400> 62
atgtcagatt cttgctcctg tccttccgca cccactatct tcatgttgtt gcagatgaag 60
cgcaccaaaa cgtctgacga gagcttcaac cccgtgtacc cctatgacac ggaaaacggt 120
cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagagagc 180
ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc 240
gccctgaaaa tgggaagtgg cctctccctg gacgacgccg gcaacctcac ctctcaagat 300
gtcaccacca ctacccctcc cctgaaaaaa accaagacca acctcagcct agaaacctca 360
gcccccctga ctgtgagcac ctcaggcgcc ctcaccctag cggccgccgc tcccctggcg 420
gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa 480
ctcaccctgg ccaccaaggg ccccctgacc gtgtctgaag gcaaactggc cttgcagacc 540
tcggccccac tgacggccgc tgacagcagc accctcaccg ttagcgccac accacccatc 600
aatgtaagca gtggaagttt gggcttagac atggaaaatc ccatgtatac tcatgacgga 660
aaactgggaa taagaattgg gggcccactg agagtagtag acagcctgca cacactgact 720
gtagttaccg gaaatggaat agctgtagat aacaatgccc tccaaactag agttacgggc 780
gccctgggtt atgacacatc aggaaaccta caactgagag ccgcgggggg tatgcgaatt 840
gatgcaaatg gccaacttat ccttgatgtg gcatacccat ttgatgctca aaacaatctc 900
agccttagac ttggtcaggg acccctgtat gtaaacacag accacaacct agatttgaat 960
tgcaacagag gtctgaccac aactaccacc aacaacacaa aaaaacttga aactaaaatt 1020
ggctcaggct tagactatga taccaatggt gctgtcatta ttaaacttgg cactggtgtc 1080
agctttgaca gcacaggcgc cctaagtgtg ggaaacactg gcgatgataa actgactctg 1140
tggacaaccc cagacccatc tccaaattgc agaattcact cagacaaaga ctgcaagttt 1200
actctagtcc taactaagtg tggaagtcaa atcctggctt ctgtcgccgc cctagcggtg 1260
tcaggaaatc tggcttcaat aacaggcacc gtttccagcg ttaccatctt tctcagattt 1320
gatcagaatg gagtgcttat ggaaaactcc tcgctagaca agcagtactg gaactttaga 1380
aatggtaatt caaccaatgc caccccctac accaatgcag ttggtttcat gccaaacctc 1440
gcagcatacc ccaagacaca gagtcagact gctaaaaaca acattgtaag tcaggtttac 1500
ttgaatgggg acaaatccaa acccatgatc cttaccatta ccctcaatgg aactaatgaa 1560
tccagtgaaa ctagccaggt gagtcactac tccatgtcat ttacgtgggc ttgggagagt 1620
gggcaatatg ccaccgaaac ctttgccacc aattccttta ccttctctta cattgctgaa 1680
caataa 1686
<210> 63
<211> 543
<212> PRT
<213> 黑猩猩腺病毒- ChAd 24纤维
<400> 63
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Leu Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ala Thr Pro Pro Ile Asn Val Ser Ser Gly Ser Leu Gly Leu Asp
180 185 190
Met Glu Asn Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
195 200 205
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220
Thr Gly Asn Gly Ile Ala Val Asp Asn Asn Ala Leu Gln Thr Arg Val
225 230 235 240
Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300
Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr
305 310 315 320
Lys Ile Gly Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335
Lys Leu Gly Thr Gly Val Ser Phe Asp Ser Thr Gly Ala Leu Ser Val
340 345 350
Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro
355 360 365
Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu
370 375 380
Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu
385 390 395 400
Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ser Ser Val
405 410 415
Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser
420 425 430
Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
435 440 445
Ala Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala
450 455 460
Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln
465 470 475 480
Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Ile Leu Thr Ile Thr
485 490 495
Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr
500 505 510
Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu
515 520 525
Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln
530 535 540
<210> 64
<211> 1335
<212> DNA
<213> 黑猩猩腺病毒- ChAd 26纤维
<400> 64
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgct gtccctgcgt ctggccgatc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agatggggtg gacctcgacg actcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360
aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420
acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480
agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540
attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600
agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660
aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720
caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780
aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840
tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcaaatccta 900
ggcactgtct ccctattagc agtcagtggc agcttggctc ctatcacagg ggctgttaga 960
actgcacttg tatcactcaa attcaatgct aatggagccc ttttggacaa atcaactctg 1020
aacaaagaat actggaacta cagacaagga gatctaattc caggtacacc atatacacat 1080
gctgtgggtt tcatgcctaa caaaaaagcc taccctaaaa acacaactgc agcttccaag 1140
agccacattg tgggtgatgt gtatttagat ggagatgcag ataaaccttt atctcttatc 1200
atcactttca atgaaactga tgatgaaacc tgtgattact gcatcaactt tcaatggaaa 1260
tggggagctg atcaatataa ggataagaca ctcgcaacca gttcattcac cttctcatac 1320
atcgcccaag aataa 1335
<210> 65
<211> 444
<212> PRT
<213> 黑猩猩腺病毒- ChAd 26纤维
<400> 65
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Asp Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln
210 215 220
Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu
225 230 235 240
Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Leu Ala Val Ser Gly Ser Leu Ala Pro Ile Thr Gly Ala Val Arg
305 310 315 320
Thr Ala Leu Val Ser Leu Lys Phe Asn Ala Asn Gly Ala Leu Leu Asp
325 330 335
Lys Ser Thr Leu Asn Lys Glu Tyr Trp Asn Tyr Arg Gln Gly Asp Leu
340 345 350
Ile Pro Gly Thr Pro Tyr Thr His Ala Val Gly Phe Met Pro Asn Lys
355 360 365
Lys Ala Tyr Pro Lys Asn Thr Thr Ala Ala Ser Lys Ser His Ile Val
370 375 380
Gly Asp Val Tyr Leu Asp Gly Asp Ala Asp Lys Pro Leu Ser Leu Ile
385 390 395 400
Ile Thr Phe Asn Glu Thr Asp Asp Glu Thr Cys Asp Tyr Cys Ile Asn
405 410 415
Phe Gln Trp Lys Trp Gly Ala Asp Gln Tyr Lys Asp Lys Thr Leu Ala
420 425 430
Thr Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 66
<211> 1062
<212> DNA
<213> 黑猩猩腺病毒- ChAd 30纤维
<400> 66
atggccaaac gagctcggct aagcagctcc ttcaatccgg tctaccccta tgaagatgaa 60
agcagctcac aacacccctt tataaaccct ggtttcattt cctcaaatgg ttttgcacaa 120
agcccagatg gagttctaac tcttaaatgt gttaatccgc tcactaccgc cagcggaccc 180
ctccaactta aagttggaag cagtcttaca gtagatacta tcgatgggtc tttggaggaa 240
aatataactg ccgcagcgcc actcactaaa actaaccact ccataggttt atcaatagga 300
tctggcttgc aaacaaagga tgataaactt tgtttatcgc tgggagatgg gttggtaaca 360
aaggatgata aactatgttt atcgctggga gatgggttaa taacaaaaga tgatacacta 420
tgtgccaaac taggacatgg ccttgtgttt gactcttcca atgctatcac catagaaaac 480
aacaccttgt ggacaggtgc aaaaccaagc gccaactgtg taattaaaga gggagaagat 540
tccccagact gtaagctcac tttagttcta gtgaagaatg gaggactgat aaatggatac 600
ataacattaa tgggagcctc agaatatact aacaccttgt ttaaaaacaa acaagttaca 660
atcgatgtaa acctcgcatt tgataatact ggccaaatta tcacttacct atcatccctt 720
aaaagtaacc tgaactttaa agacaaccaa aacatggcta ctggaaccat aaccagtgcc 780
aaaggcttca tgcccagcac caccgcctat ccatttataa catacgccac tcagtcccta 840
aatgaagatt acatttatgg agagtgttac tacaaatcta ccaatggaac tctctttcca 900
ctaaaagtta ctgtcacact aaacagacgt atgtcagctt ctggaatggc ctatgctatg 960
aatttttcat ggtctctaaa tgcagaggaa gccccggaaa ctaccgaagt cactctcatt 1020
acctccccct tctttttttc ttatatcaga gaagatgact ga 1062
<210> 67
<211> 353
<212> PRT
<213> 黑猩猩腺病毒- ChAd 30纤维
<400> 67
Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe
20 25 30
Ile Ser Ser Asn Gly Phe Ala Gln Ser Pro Asp Gly Val Leu Thr Leu
35 40 45
Lys Cys Val Asn Pro Leu Thr Thr Ala Ser Gly Pro Leu Gln Leu Lys
50 55 60
Val Gly Ser Ser Leu Thr Val Asp Thr Ile Asp Gly Ser Leu Glu Glu
65 70 75 80
Asn Ile Thr Ala Ala Ala Pro Leu Thr Lys Thr Asn His Ser Ile Gly
85 90 95
Leu Ser Ile Gly Ser Gly Leu Gln Thr Lys Asp Asp Lys Leu Cys Leu
100 105 110
Ser Leu Gly Asp Gly Leu Val Thr Lys Asp Asp Lys Leu Cys Leu Ser
115 120 125
Leu Gly Asp Gly Leu Ile Thr Lys Asp Asp Thr Leu Cys Ala Lys Leu
130 135 140
Gly His Gly Leu Val Phe Asp Ser Ser Asn Ala Ile Thr Ile Glu Asn
145 150 155 160
Asn Thr Leu Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile Lys
165 170 175
Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val Lys
180 185 190
Asn Gly Gly Leu Ile Asn Gly Tyr Ile Thr Leu Met Gly Ala Ser Glu
195 200 205
Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val Asn
210 215 220
Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser Leu
225 230 235 240
Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly Thr
245 250 255
Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro Phe
260 265 270
Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly Glu
275 280 285
Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val Thr
290 295 300
Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala Met
305 310 315 320
Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr Glu
325 330 335
Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu Asp
340 345 350
Asp
<210> 68
<211> 1791
<212> DNA
<213> 黑猩猩腺病毒- ChAd 31纤维
<400> 68
atgtcagatt cttgctcctg tccctccgca cccactatct tcatgttgtt gcagatgaag 60
cgcaccaaaa cgtctgacga gagcttcaac cccgtgtacc cctatgacac ggaaagcggc 120
cctccctccg tccctttcct cacccctccc ttcgtgtctc ccgatggatt ccaagaaagt 180
ccccccgggg tcctgtctct gaacctggcc gagcccctgg tcacttccca cggcatgctc 240
gccctgaaaa tgggaagtgg cctctccctg gacgacgctg gcaacctcac ctctcaagat 300
atcaccaccg ctagccctcc cctcaaaaaa accaagacca acctcagcct agaaacctca 360
tcccccctaa ctgtgagcac ctcaggcgcc ctcaccgtag cagccgccgc tcccctggcg 420
gtggccggca cctccctcac catgcaatca gaggcccccc tgacagtaca ggatgcaaaa 480
ctcaccctgg ccaccaaagg ccccctgacc gtgtctgaag gcaaactggc cttgcaaaca 540
tcggccccgc tgacggccgc tgacagcagc accctcacag tcagtgccac accacccctt 600
agcacaagca atggcagctt gggtattgac atgcaagccc ccatttacac caccaatgga 660
aaactaggac ttaactttgg cgctcccctg catgtggtag acagcctaaa tgcactgact 720
gtagttactg gccaaggtct tacgataaac ggaacagccc tacaaactag agtctcaggt 780
gccctcaact atgacacatc aggaaaccta gaattgagag ctgcaggggg tatgcgagtt 840
gatgcaaatg gtcaacttat ccttgatgta gcttacccat ttgatgcaca aaacaatctc 900
agccttaggc ttggacaggg acccctgttt gttaactctg cccacaactt ggatgttaac 960
tacaacagag gcctctacct gttcacatct ggaaatacca aaaagctaga agttaatatc 1020
aaaacagcca agggtctcat ttatgatgac actgctatag caatcaatgc gggtgatggg 1080
ctacagtttg actcaggctc agatacaaat ccattaaaaa ctaaacttgg attaggactg 1140
gattatgact ccagcagagc cataattgct aaactgggaa ctggcctaag ctttgacaac 1200
acaggtgcca tcacagtagg caacaaaaat gatgacaagc ttaccttgtg gaccacacca 1260
gacccatccc ctaactgtag aatctattca gagaaagatg ctaaattcac acttgttttg 1320
actaaatgcg gcagtcaggt gttggccagc gtttctgttt tatctgtaaa aggtagcctt 1380
gcgcccatca gtggcacagt aactagtgct cagattgtcc tcagatttga tgaaaatgga 1440
gttctactaa gcaattcttc ccttgaccct caatactgga actacagaaa aggtgacctt 1500
acagagggca ctgcatatac caacgcagtg ggatttatgc ccaacctcac agcataccca 1560
aaaacacaga gccaaactgc taaaagcaac attgtaagtc aggtttactt gaatggggac 1620
aaatccaaac ccatgaccct caccattacc ctcaatggaa ctaatgaaac aggagatgcc 1680
acagtaagca cttactccat gtcattctca tggaactgga atggaagtaa ttacattaat 1740
gaaacgttcc aaaccaactc cttcaccttc tcctacatcg cccaagaata a 1791
<210> 69
<211> 578
<212> PRT
<213> 黑猩猩腺病毒- ChAd 31纤维
<400> 69
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp
180 185 190
Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe
195 200 205
Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val
210 215 220
Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val
225 230 235 240
Ser Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn Tyr Asn
290 295 300
Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu Glu Val
305 310 315 320
Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala Ile Ala
325 330 335
Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp Ser Gly Ser Asp Thr Asn
340 345 350
Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Asp Tyr Asp Ser Ser Arg
355 360 365
Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly
370 375 380
Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu Trp Thr
385 390 395 400
Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala
405 410 415
Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser
420 425 430
Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr
435 440 445
Val Thr Ser Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly Val Leu
450 455 460
Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly
465 470 475 480
Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro
485 490 495
Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser Asn
500 505 510
Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr
515 520 525
Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala Thr Val
530 535 540
Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser Asn Tyr
545 550 555 560
Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala
565 570 575
Gln Glu
<210> 70
<211> 978
<212> DNA
<213> 黑猩猩腺病毒- ChAd 37纤维
<400> 70
atggccaaac gggctcgtct aagcagctcc ttcaacccgg tgtaccccta tgaagacgag 60
agcagctcac aacacccatt tataaacccc ggcttcattt cccctgatgg ctttacacaa 120
agcccagacg gagttctaac actgaaatgt gtttcccctc ttactaccac cagtggcgct 180
ctagacatta aagtgggaag agggcttaaa gtagatagca ctgatggttc cctggaagaa 240
aatatagaca ttacagctcc cctcactaaa tttaaccact cagtaggatt agcatttggc 300
gacggtctag aaacaaaaga aaacaagctt tatgtaaaac ttggagatgg acttaaattt 360
agctctggca gtatatacat tgaccatgat gttaacactt tatggacagg agtcaatcca 420
agtgctaact gtataattac agacaatgga gaaaccaatg acagcaagct taccctaata 480
cttgttaagt caggtggatt aataaatgct tatgtctcat taatgggtga ctcagacaca 540
gtcaataaat taaccacaga aaaaagtgct caaattaccg ttgacatata ctttgataat 600
caaggaaaag ttcttactga actatcggcc cttaaaacag atcttaaaca taaatttggt 660
caaaacatgg cttctagcga agtatcaaac tgcaaaggct ttatgccaag cttaaatgca 720
tacccattca gaaatccaac taaacctacc aaaggaagag aagactacat ttatggaata 780
acttactatc aagccacaga tggtaatctc tatgagctaa aaactactat tactctaaac 840
cacagtgtca ttagttctct atgtgcatat gcaatgcaca tttcatggtc atgggacacc 900
gtaacagagc cagagacaac acccactact cttattacct cccccttctc cttttcctat 960
atcagagaag atgactga 978
<210> 71
<211> 325
<212> PRT
<213> 黑猩猩腺病毒- ChAd 37纤维
<400> 71
Met Ala Lys Arg Ala Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Glu Asp Glu Ser Ser Ser Gln His Pro Phe Ile Asn Pro Gly Phe
20 25 30
Ile Ser Pro Asp Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu
35 40 45
Lys Cys Val Ser Pro Leu Thr Thr Thr Ser Gly Ala Leu Asp Ile Lys
50 55 60
Val Gly Arg Gly Leu Lys Val Asp Ser Thr Asp Gly Ser Leu Glu Glu
65 70 75 80
Asn Ile Asp Ile Thr Ala Pro Leu Thr Lys Phe Asn His Ser Val Gly
85 90 95
Leu Ala Phe Gly Asp Gly Leu Glu Thr Lys Glu Asn Lys Leu Tyr Val
100 105 110
Lys Leu Gly Asp Gly Leu Lys Phe Ser Ser Gly Ser Ile Tyr Ile Asp
115 120 125
His Asp Val Asn Thr Leu Trp Thr Gly Val Asn Pro Ser Ala Asn Cys
130 135 140
Ile Ile Thr Asp Asn Gly Glu Thr Asn Asp Ser Lys Leu Thr Leu Ile
145 150 155 160
Leu Val Lys Ser Gly Gly Leu Ile Asn Ala Tyr Val Ser Leu Met Gly
165 170 175
Asp Ser Asp Thr Val Asn Lys Leu Thr Thr Glu Lys Ser Ala Gln Ile
180 185 190
Thr Val Asp Ile Tyr Phe Asp Asn Gln Gly Lys Val Leu Thr Glu Leu
195 200 205
Ser Ala Leu Lys Thr Asp Leu Lys His Lys Phe Gly Gln Asn Met Ala
210 215 220
Ser Ser Glu Val Ser Asn Cys Lys Gly Phe Met Pro Ser Leu Asn Ala
225 230 235 240
Tyr Pro Phe Arg Asn Pro Thr Lys Pro Thr Lys Gly Arg Glu Asp Tyr
245 250 255
Ile Tyr Gly Ile Thr Tyr Tyr Gln Ala Thr Asp Gly Asn Leu Tyr Glu
260 265 270
Leu Lys Thr Thr Ile Thr Leu Asn His Ser Val Ile Ser Ser Leu Cys
275 280 285
Ala Tyr Ala Met His Ile Ser Trp Ser Trp Asp Thr Val Thr Glu Pro
290 295 300
Glu Thr Thr Pro Thr Thr Leu Ile Thr Ser Pro Phe Ser Phe Ser Tyr
305 310 315 320
Ile Arg Glu Asp Asp
325
<210> 72
<211> 1332
<212> DNA
<213> 黑猩猩腺病毒- ChAd 38纤维
<400> 72
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgtt gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggataccc ctttttatac caaagatgga aaattatcct tacaagtttc tccaccatta 360
aacatattaa aatcaaccat tctgaacaca ttagctgtag cttatggatc aggtttagga 420
ctcagtggtg gcactgctct tgcagtacag ttggcctctc cactcacctt tgatgaaaaa 480
ggaaatatta aaattaacct agccagtggt ccattaacag ttgatgcaag tcgacttagt 540
atcaactgca aaagaggggt cactgtcact accgcaggag atgcaattaa aagcaacata 600
agctggccta aaggtataag atttgaaggt gatgccatag ctgcaaacat tggcagagga 660
ttggaatttg gaaccactag tacagagact gatgtcacag atgcataccc aattcaagtt 720
aaattgggta ctggtctcac ctttgacagt acaggcgcca ttgttgcatg gaacaaagag 780
gatgataaac ttacattatg gaccacagcc gacccctcgc caaattgcaa aatatactct 840
gaaaaagatg ctaaactcac actttgcttg acaaaatgtg gaagccaaat tctgggcact 900
gtgactgtat tggcagtgaa taatggaagt ctcaacccaa tcacaaacac agtaagcact 960
gcacttgtct ccctcaagtt tgatgcaagt ggagttttgc taagcagctc cacattagac 1020
aaagaatatt ggaacttccg aaagggagat gttacacctg ctgaacccta tactaatgct 1080
ataggtttta tgcctaacat aaaggcctat cctaaaaaca catctgcagc ttcaaaaagc 1140
catattgtca gtcaagttta tctcaatggg gatgaaacca aacctctgat gctgattatt 1200
acttttaatg aaactgagga tgcaacttgc acctatagta tcacttttca atggaaatgg 1260
gatagtacta agtacacagg taaaacactt gctaccagct ccttcacctt ctcctacatt 1320
gctcaagaat ga 1332
<210> 73
<211> 443
<212> PRT
<213> 黑猩猩腺病毒- ChAd 38纤维
<400> 73
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Lys Ser Thr Ile Leu
115 120 125
Asn Thr Leu Ala Val Ala Tyr Gly Ser Gly Leu Gly Leu Ser Gly Gly
130 135 140
Thr Ala Leu Ala Val Gln Leu Ala Ser Pro Leu Thr Phe Asp Glu Lys
145 150 155 160
Gly Asn Ile Lys Ile Asn Leu Ala Ser Gly Pro Leu Thr Val Asp Ala
165 170 175
Ser Arg Leu Ser Ile Asn Cys Lys Arg Gly Val Thr Val Thr Thr Ala
180 185 190
Gly Asp Ala Ile Lys Ser Asn Ile Ser Trp Pro Lys Gly Ile Arg Phe
195 200 205
Glu Gly Asp Ala Ile Ala Ala Asn Ile Gly Arg Gly Leu Glu Phe Gly
210 215 220
Thr Thr Ser Thr Glu Thr Asp Val Thr Asp Ala Tyr Pro Ile Gln Val
225 230 235 240
Lys Leu Gly Thr Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile Val Ala
245 250 255
Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala Asp Pro
260 265 270
Ser Pro Asn Cys Lys Ile Tyr Ser Glu Lys Asp Ala Lys Leu Thr Leu
275 280 285
Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Thr Val Leu
290 295 300
Ala Val Asn Asn Gly Ser Leu Asn Pro Ile Thr Asn Thr Val Ser Thr
305 310 315 320
Ala Leu Val Ser Leu Lys Phe Asp Ala Ser Gly Val Leu Leu Ser Ser
325 330 335
Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp Val Thr
340 345 350
Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn Ile Lys
355 360 365
Ala Tyr Pro Lys Asn Thr Ser Ala Ala Ser Lys Ser His Ile Val Ser
370 375 380
Gln Val Tyr Leu Asn Gly Asp Glu Thr Lys Pro Leu Met Leu Ile Ile
385 390 395 400
Thr Phe Asn Glu Thr Glu Asp Ala Thr Cys Thr Tyr Ser Ile Thr Phe
405 410 415
Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Lys Thr Leu Ala Thr
420 425 430
Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 74
<211> 1332
<212> DNA
<213> 黑猩猩腺病毒- ChAd 44纤维
<400> 74
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgtt gtccctgcga ctggctgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cgtcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtatttcaa acaacaccat ttcccttaaa 300
actgctgccc ctttctacaa caacaatgga actttaagcc tcaatgtctc cacaccatta 360
gcagtatttc ccacatttaa cactttaggc ataagtcttg gaaacggtct tcagacttca 420
aataagttgt tgactgtaca actaactcat cctcttacat tcagctcaaa tagcatcaca 480
gtaaaaacag acaaagggct atatattaac tccagtggaa acagaggact tgaggctaat 540
ataagcctaa aaagaggact agtttttgac ggtaatgcta ttgcaacata tattggaaat 600
ggcttagact atggatctta tgatagtgat ggaaaaacaa gacccgtaat taccaaaatt 660
ggagcaggat taaattttga tgctaacaaa gcaatagctg tcaaactagg cacaggttta 720
agttttgact ccgctggtgc cttgacagct ggaaacaaac aggatgacaa gctaacactt 780
tggactaccc ctgacccaag ccctaattgt caattacttt cagacagaga tgccaaattt 840
actctctgtc ttacaaaatg cggtagtcaa atactaggca ctgtggcagt ggcggctgtt 900
actgtaggat cagcactaaa tccaattaat gacacagtca aaagcgccat agttttcctt 960
agatttgatt ccgatggtgt actcatgtca aactcatcaa tggtaggtga ttactggaac 1020
tttagggagg gacagaccac tcaaagtgta gcctatacaa atgctgtggg attcatgcca 1080
aatataggtg catatccaaa aacccaaagt aaaacaccta aaaatagcat agtcagtcag 1140
gtatatttaa ctggagaaac tactatgcca atgacactaa ccataacttt caatggcact 1200
gatgaaaaag acacaacccc agttagcacc tactctatga cttttacatg gcagtggact 1260
ggagactata aggacaaaaa tattaccttt gctaccaact cattctcttt ttcctacatc 1320
gcccaggaat aa 1332
<210> 75
<211> 443
<212> PRT
<213> 黑猩猩腺病毒- ChAd 44纤维
<400> 75
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Ile Ser Asn Asn Thr
85 90 95
Ile Ser Leu Lys Thr Ala Ala Pro Phe Tyr Asn Asn Asn Gly Thr Leu
100 105 110
Ser Leu Asn Val Ser Thr Pro Leu Ala Val Phe Pro Thr Phe Asn Thr
115 120 125
Leu Gly Ile Ser Leu Gly Asn Gly Leu Gln Thr Ser Asn Lys Leu Leu
130 135 140
Thr Val Gln Leu Thr His Pro Leu Thr Phe Ser Ser Asn Ser Ile Thr
145 150 155 160
Val Lys Thr Asp Lys Gly Leu Tyr Ile Asn Ser Ser Gly Asn Arg Gly
165 170 175
Leu Glu Ala Asn Ile Ser Leu Lys Arg Gly Leu Val Phe Asp Gly Asn
180 185 190
Ala Ile Ala Thr Tyr Ile Gly Asn Gly Leu Asp Tyr Gly Ser Tyr Asp
195 200 205
Ser Asp Gly Lys Thr Arg Pro Val Ile Thr Lys Ile Gly Ala Gly Leu
210 215 220
Asn Phe Asp Ala Asn Lys Ala Ile Ala Val Lys Leu Gly Thr Gly Leu
225 230 235 240
Ser Phe Asp Ser Ala Gly Ala Leu Thr Ala Gly Asn Lys Gln Asp Asp
245 250 255
Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Gln Leu
260 265 270
Leu Ser Asp Arg Asp Ala Lys Phe Thr Leu Cys Leu Thr Lys Cys Gly
275 280 285
Ser Gln Ile Leu Gly Thr Val Ala Val Ala Ala Val Thr Val Gly Ser
290 295 300
Ala Leu Asn Pro Ile Asn Asp Thr Val Lys Ser Ala Ile Val Phe Leu
305 310 315 320
Arg Phe Asp Ser Asp Gly Val Leu Met Ser Asn Ser Ser Met Val Gly
325 330 335
Asp Tyr Trp Asn Phe Arg Glu Gly Gln Thr Thr Gln Ser Val Ala Tyr
340 345 350
Thr Asn Ala Val Gly Phe Met Pro Asn Ile Gly Ala Tyr Pro Lys Thr
355 360 365
Gln Ser Lys Thr Pro Lys Asn Ser Ile Val Ser Gln Val Tyr Leu Thr
370 375 380
Gly Glu Thr Thr Met Pro Met Thr Leu Thr Ile Thr Phe Asn Gly Thr
385 390 395 400
Asp Glu Lys Asp Thr Thr Pro Val Ser Thr Tyr Ser Met Thr Phe Thr
405 410 415
Trp Gln Trp Thr Gly Asp Tyr Lys Asp Lys Asn Ile Thr Phe Ala Thr
420 425 430
Asn Ser Phe Ser Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 76
<211> 1278
<212> DNA
<213> 黑猩猩腺病毒- ChAd 63纤维
<400> 76
atgtccaaaa agcgcgtccg ggtggatgat gacttcgacc ccgtctaccc ctacgatgca 60
gacaacgcac cgaccgtgcc cttcatcaac ccccccttcg tctcttcaga tggattccaa 120
gagaagcccc tgggggtgct gtccctgcga ctggccgacc ccgtcaccac caagaacggg 180
gaaatcaccc tcaagctggg agagggggtg gacctcgact cctcgggaaa actcatctcc 240
aacacggcca ccaaggccgc cgcccctctc agtttttcca acaacaccat ttcccttaac 300
atggatcacc ccttttacac taaagatgga aaattatcct tacaagtttc tccaccatta 360
aatatactga gaacaagcat tctaaacaca ctagctttag gttttggatc aggtttagga 420
ctccgtggct ctgccttggc agtacagtta gtctctccac ttacatttga tactgatgga 480
aacataaagc ttaccttaga cagaggtttg catgttacaa caggagatgc aattgaaagc 540
aacataagct gggctaaagg tttaaaattt gaagatggag ccatagcaac caacattgga 600
aatgggttag agtttggaag cagtagtaca gaaacaggtg ttgatgatgc ttacccaatc 660
caagttaaac ttggatctgg ccttagcttt gacagtacag gagccataat ggctggtaac 720
aaagaagacg ataaactcac tttgtggaca acacctgatc catcgccaaa ctgtcaaata 780
ctcgcagaaa atgatgcaaa actaacactt tgcttgacta aatgtggtag tcaaatactg 840
gccactgtgt cagtcttagt tgtaggaagt ggaaacctaa accccattac tggcaccgta 900
agcagtgctc aggtgtttct acgttttgat gcaaacggtg ttcttttaac agaacattct 960
acactaaaaa aatactgggg gtataggcag ggagatagca tagatggcac tccatatacc 1020
aatgctgtag gattcatgcc caatttaaaa gcttatccaa agtcacaaag ttctactact 1080
aaaaataata tagtagggca agtatacatg aatggagatg tttcaaaacc tatgcttctc 1140
actataaccc tcaatggtac tgatgacagc aacagtacat attcaatgtc attttcatac 1200
acctggacta atggaagcta tgttggagca acatttgggg ctaactctta taccttctca 1260
tacatcgccc aagaatga 1278
<210> 77
<211> 425
<212> PRT
<213> 黑猩猩腺病毒- ChAd 63纤维
<400> 77
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu
115 120 125
Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser
130 135 140
Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly
145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp
165 170 175
Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp
180 185 190
Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser
195 200 205
Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu
210 215 220
Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn
225 230 235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
245 250 255
Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu
260 265 270
Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val
275 280 285
Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300
Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser
305 310 315 320
Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly
325 330 335
Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350
Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val
355 360 365
Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu
370 375 380
Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400
Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser
405 410 415
Tyr Thr Phe Ser Tyr Ile Ala Gln Glu
420 425
<210> 78
<211> 1338
<212> DNA
<213> 黑猩猩腺病毒- ChAd 82纤维
<400> 78
atgtccaaaa agcgcgcgcg ggtggatgat gacttcgacc ccgtgtaccc ctacgatgca 60
gacaacgcac cgactgtgcc cttcatcaac cctcccttcg tctcttcaga tggattccaa 120
gaaaagcccc tgggggtgtt gtccctgcga ctggccgatc ccgtcaccac caagaacggg 180
gctgtcaccc tcaagctggg ggagggggtg gacctcgacg actcgggaaa actcatctcc 240
aaaaatgcca ccaaggccac tgcccctctc agtatttcca acaacaccat ttcccttaac 300
atggataccc ctctttacaa caacaatgga aagctaggta tgaaggtaac cgcaccatta 360
aagatattag acacagatct actaaaaaca cttgttgttg cttatgggca gggattagga 420
acaaacacca atggtgctct tgttgcccaa ctagcatacc cacttgtttt taataccgct 480
agcaaaattg cccttaattt aggcaatgga ccattaaaag tggatgcaaa tagactgaac 540
attaattgca aaagaggtat ctatgtcact accacaaaag atgcactgga gattaatatc 600
agttgggcaa atgctatgac atttatagga aatgccattg gtgtcaatat tgacacaaaa 660
aaaggcctac agttcggcac ttcaagcact gaaacagatg ttaaaaatgc ttttccactc 720
caagtaaaac ttggagctgg tcttacattt gacagcacag gtgccattgt tgcttggaac 780
aaagaagatg acaaacttac actgtggacc acagccgatc catctccaaa ctgtcacata 840
tattctgcaa aggatgctaa gcttacactc tgcttgacaa agtgtggtag tcagatactg 900
ggcactgttt ctctcatagc tgttgatact ggtagcttaa atccaataac aggaaaagta 960
accactgctc ttgtttcact taaattcgat gccaatggag ttttgcaagc cagttcaaca 1020
ctagataaag aatattggaa tttcagaaaa ggagatgtga cacctgctga cccctacact 1080
aatgctatag gctttatgcc caaccttaat gcatacccaa aaaacacaaa cgcagctgca 1140
aaaagtcaca ttgttggaaa agtataccta catggggatg taagcaagcc actagacttg 1200
ataattacat ttaatgaaac cagtgatgaa tcctgtactt attgcattaa ctttcagtgg 1260
cggtggggaa ctgaccaata taaagatgaa acacttgcag tcagttcatt caccttctca 1320
tacattgcta aagaataa 1338
<210> 79
<211> 445
<212> PRT
<213> 黑猩猩腺病毒- ChAd 82纤维
<400> 79
Met Ser Lys Lys Arg Ala Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Ala Val Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser
65 70 75 80
Lys Asn Ala Thr Lys Ala Thr Ala Pro Leu Ser Ile Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln
210 215 220
Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu
225 230 235 240
Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Lys Val
305 310 315 320
Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln
325 330 335
Ala Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp
340 345 350
Val Thr Pro Ala Asp Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn
355 360 365
Leu Asn Ala Tyr Pro Lys Asn Thr Asn Ala Ala Ala Lys Ser His Ile
370 375 380
Val Gly Lys Val Tyr Leu His Gly Asp Val Ser Lys Pro Leu Asp Leu
385 390 395 400
Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile
405 410 415
Asn Phe Gln Trp Arg Trp Gly Thr Asp Gln Tyr Lys Asp Glu Thr Leu
420 425 430
Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu
435 440 445
<210> 80
<211> 445
<212> PRT
<213> 黑猩猩腺病毒- CV23/Pan5纤维
<400> 80
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Asp Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Phe Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Thr
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Ser Pro Leu Ala Phe Asp Ser Asn
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Asn Arg Gly Leu Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Ala Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Met Gly Val Asn Ile Asp Thr Gln Lys Gly Leu Gln
210 215 220
Phe Gly Thr Thr Ser Thr Val Ala Asp Val Lys Asn Ala Tyr Pro Ile
225 230 235 240
Gln Ile Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Asp Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Glu Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Thr Val
305 310 315 320
Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln
325 330 335
Ser Ser Ser Thr Leu Asp Ser Asp Tyr Trp Asn Phe Arg Gln Gly Asp
340 345 350
Val Thr Pro Ala Glu Ala Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn
355 360 365
Leu Lys Ala Tyr Pro Lys Asn Thr Ser Gly Ala Ala Lys Ser His Ile
370 375 380
Val Gly Lys Val Tyr Leu His Gly Asp Thr Gly Lys Pro Leu Asp Leu
385 390 395 400
Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile
405 410 415
Asn Phe Gln Trp Gln Trp Gly Ala Asp Gln Tyr Lys Asn Glu Thr Leu
420 425 430
Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu
435 440 445
<210> 81
<211> 443
<212> PRT
<213> 黑猩猩腺病毒- CV32/Pan6纤维
<400> 81
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Ile Ser Asn Asn Thr
85 90 95
Ile Ser Leu Lys Thr Ala Ala Pro Phe Tyr Asn Asn Asn Gly Thr Leu
100 105 110
Ser Leu Asn Val Ser Thr Pro Leu Ala Val Phe Pro Thr Phe Asn Thr
115 120 125
Leu Gly Ile Ser Leu Gly Asn Gly Leu Gln Thr Ser Asn Lys Leu Leu
130 135 140
Thr Val Gln Leu Thr His Pro Leu Thr Phe Ser Ser Asn Ser Ile Thr
145 150 155 160
Val Lys Thr Asp Lys Gly Leu Tyr Ile Asn Ser Ser Gly Asn Arg Gly
165 170 175
Leu Glu Ala Asn Ile Ser Leu Lys Arg Gly Leu Val Phe Asp Gly Asn
180 185 190
Ala Ile Ala Thr Tyr Ile Gly Asn Gly Leu Asp Tyr Gly Ser Tyr Asp
195 200 205
Ser Asp Gly Lys Thr Arg Pro Val Ile Thr Lys Ile Gly Ala Gly Leu
210 215 220
Asn Phe Asp Ala Asn Lys Ala Ile Ala Val Lys Leu Gly Thr Gly Leu
225 230 235 240
Ser Phe Asp Ser Ala Gly Ala Leu Thr Ala Gly Asn Lys Gln Asp Asp
245 250 255
Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Gln Leu
260 265 270
Leu Ser Asp Arg Asp Ala Lys Phe Thr Leu Cys Leu Thr Lys Cys Gly
275 280 285
Ser Gln Ile Leu Gly Thr Val Ala Val Ala Ala Val Thr Val Gly Ser
290 295 300
Ala Leu Asn Pro Ile Asn Asp Thr Val Lys Ser Ala Ile Val Phe Leu
305 310 315 320
Arg Phe Asp Ser Asp Gly Val Leu Met Ser Asn Ser Ser Met Val Gly
325 330 335
Asp Tyr Trp Asn Phe Arg Glu Gly Gln Thr Thr Gln Ser Val Ala Tyr
340 345 350
Thr Asn Ala Val Gly Phe Met Pro Asn Ile Gly Ala Tyr Pro Lys Thr
355 360 365
Gln Ser Lys Thr Pro Lys Asn Ser Ile Val Ser Gln Val Tyr Leu Thr
370 375 380
Gly Glu Thr Thr Met Pro Met Thr Leu Thr Ile Thr Phe Asn Gly Thr
385 390 395 400
Asp Glu Lys Asp Thr Thr Pro Val Ser Thr Tyr Ser Met Thr Phe Thr
405 410 415
Trp Gln Trp Thr Gly Asp Tyr Lys Asp Lys Asn Ile Thr Phe Ala Thr
420 425 430
Asn Ser Phe Ser Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 82
<211> 443
<212> PRT
<213> 黑猩猩腺病毒- CV33/Pan7纤维
<400> 82
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Lys Ser Thr Ile Leu
115 120 125
Asn Thr Leu Ala Val Ala Tyr Gly Ser Gly Leu Gly Leu Ser Gly Gly
130 135 140
Thr Ala Leu Ala Val Gln Leu Ala Ser Pro Leu Thr Phe Asp Glu Lys
145 150 155 160
Gly Asn Ile Lys Ile Asn Leu Ala Ser Gly Pro Leu Thr Val Asp Ala
165 170 175
Ser Arg Leu Ser Ile Asn Cys Lys Arg Gly Val Thr Val Thr Thr Ser
180 185 190
Gly Asp Ala Ile Glu Ser Asn Ile Ser Trp Pro Lys Gly Ile Arg Phe
195 200 205
Glu Gly Asn Gly Ile Ala Ala Asn Ile Gly Arg Gly Leu Glu Phe Gly
210 215 220
Thr Thr Ser Thr Glu Thr Asp Val Thr Asp Ala Tyr Pro Ile Gln Val
225 230 235 240
Lys Leu Gly Thr Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile Val Ala
245 250 255
Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala Asp Pro
260 265 270
Ser Pro Asn Cys Lys Ile Tyr Ser Glu Lys Asp Ala Lys Leu Thr Leu
275 280 285
Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Thr Val Leu
290 295 300
Ala Val Asn Asn Gly Ser Leu Asn Pro Ile Thr Asn Thr Val Ser Thr
305 310 315 320
Ala Leu Val Ser Leu Lys Phe Asp Ala Ser Gly Val Leu Leu Ser Ser
325 330 335
Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp Val Thr
340 345 350
Pro Ala Glu Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn Ile Lys
355 360 365
Ala Tyr Pro Lys Asn Thr Ser Ala Ala Ser Lys Ser His Ile Val Ser
370 375 380
Gln Val Tyr Leu Asn Gly Asp Glu Ala Lys Pro Leu Met Leu Ile Ile
385 390 395 400
Thr Phe Asn Glu Thr Glu Asp Ala Thr Cys Thr Tyr Ser Ile Thr Phe
405 410 415
Gln Trp Lys Trp Asp Ser Thr Lys Tyr Thr Gly Glu Thr Leu Ala Thr
420 425 430
Ser Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
435 440
<210> 83
<211> 543
<212> PRT
<213> 黑猩猩腺病毒- ChAd 3纤维
<400> 83
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ala Thr Pro Pro Ile Asn Val Ser Ser Gly Ser Leu Gly Leu Asp
180 185 190
Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
195 200 205
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220
Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr Arg Val
225 230 235 240
Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asn Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Tyr Ile Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300
Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr
305 310 315 320
Lys Ile Ser Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335
Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Leu Thr Val
340 345 350
Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro
355 360 365
Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu
370 375 380
Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu
385 390 395 400
Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val
405 410 415
Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser
420 425 430
Ser Leu Asp Arg Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
435 440 445
Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala
450 455 460
Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln
465 470 475 480
Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr
485 490 495
Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr
500 505 510
Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu
515 520 525
Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln
530 535 540
<210> 84
<211> 445
<212> PRT
<213> 黑猩猩腺病毒- ChAd 6纤维
<400> 84
Met Ser Lys Lys Arg Ala Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Ala Val Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Asp Ser Gly Lys Leu Ile Ser
65 70 75 80
Lys Asn Ala Thr Lys Ala Thr Ala Pro Leu Ser Ile Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp Thr Pro Leu Tyr Asn Asn Asn Gly Lys Leu
100 105 110
Gly Met Lys Val Thr Ala Pro Leu Lys Ile Leu Asp Thr Asp Leu Leu
115 120 125
Lys Thr Leu Val Val Ala Tyr Gly Gln Gly Leu Gly Thr Asn Thr Asn
130 135 140
Gly Ala Leu Val Ala Gln Leu Ala Tyr Pro Leu Val Phe Asn Thr Ala
145 150 155 160
Ser Lys Ile Ala Leu Asn Leu Gly Asn Gly Pro Leu Lys Val Asp Ala
165 170 175
Asn Arg Leu Asn Ile Asn Cys Lys Arg Gly Ile Tyr Val Thr Thr Thr
180 185 190
Lys Asp Ala Leu Glu Ile Asn Ile Ser Trp Ala Asn Ala Met Thr Phe
195 200 205
Ile Gly Asn Ala Ile Gly Val Asn Ile Asp Thr Lys Lys Gly Leu Gln
210 215 220
Phe Gly Thr Ser Ser Thr Glu Thr Asp Val Lys Asn Ala Phe Pro Leu
225 230 235 240
Gln Val Lys Leu Gly Ala Gly Leu Thr Phe Asp Ser Thr Gly Ala Ile
245 250 255
Val Ala Trp Asn Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Ala
260 265 270
Asp Pro Ser Pro Asn Cys His Ile Tyr Ser Ala Lys Asp Ala Lys Leu
275 280 285
Thr Leu Cys Leu Thr Lys Cys Gly Ser Gln Ile Leu Gly Thr Val Ser
290 295 300
Leu Ile Ala Val Asp Thr Gly Ser Leu Asn Pro Ile Thr Gly Lys Val
305 310 315 320
Thr Thr Ala Leu Val Ser Leu Lys Phe Asp Ala Asn Gly Val Leu Gln
325 330 335
Ala Ser Ser Thr Leu Asp Lys Glu Tyr Trp Asn Phe Arg Lys Gly Asp
340 345 350
Val Thr Pro Ala Asp Pro Tyr Thr Asn Ala Ile Gly Phe Met Pro Asn
355 360 365
Leu Asn Ala Tyr Pro Lys Asn Thr Asn Ala Ala Ala Lys Ser His Ile
370 375 380
Val Gly Lys Val Tyr Leu His Gly Asp Glu Ser Lys Pro Leu Asp Leu
385 390 395 400
Ile Ile Thr Phe Asn Glu Thr Ser Asp Glu Ser Cys Thr Tyr Cys Ile
405 410 415
Asn Phe Gln Trp Gln Trp Gly Thr Asp Gln Tyr Lys Asp Glu Thr Leu
420 425 430
Ala Val Ser Ser Phe Thr Phe Ser Tyr Ile Ala Lys Glu
435 440 445
<210> 85
<211> 322
<212> PRT
<213> 黑猩猩腺病毒- C1纤维
<400> 85
Met Ala Lys Arg Thr Arg Leu Ser Ser Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Glu Asp Glu Asn Ser Ser His Pro Phe Ile Asn Pro Gly Phe Ile
20 25 30
Ser Pro Asn Gly Phe Thr Gln Ser Pro Asp Gly Val Leu Thr Leu Asn
35 40 45
Cys Val Ala Pro Leu Thr Thr Ala Asn Gly Ala Leu Asp Ile Lys Val
50 55 60
Gly Gly Gly Leu Lys Val Asn Ser Thr Asp Gly Phe Leu Glu Glu Asn
65 70 75 80
Ile Asn Ile Thr Ser Pro Leu Thr Lys Ser Asn His Ser Ile Gly Leu
85 90 95
Glu Trp Ser Asp Gly Leu Gln Thr Asn Glu Ala Lys Leu Cys Val Lys
100 105 110
Leu Gly Lys Gly Leu Val Phe Asp Ser Ser Ser Ala Ile Ala Met Glu
115 120 125
Asn Asn Thr Leu Trp Thr Gly Ala Lys Pro Ser Ala Asn Cys Val Ile
130 135 140
Lys Glu Gly Glu Asp Ser Pro Asp Cys Lys Leu Thr Leu Val Leu Val
145 150 155 160
Lys Asn Gly Gly Leu Val Asn Gly Tyr Ile Thr Leu Met Gly Asp Ser
165 170 175
Glu Tyr Thr Asn Thr Leu Phe Lys Asn Lys Gln Val Thr Ile Asp Val
180 185 190
Asn Leu Ala Phe Asp Asn Thr Gly Gln Ile Ile Thr Tyr Leu Ser Ser
195 200 205
Leu Lys Ser Asn Leu Asn Phe Lys Asp Asn Gln Asn Met Ala Thr Gly
210 215 220
Thr Ile Thr Ser Ala Lys Gly Phe Met Pro Ser Thr Thr Ala Tyr Pro
225 230 235 240
Phe Ile Thr Tyr Ala Thr Gln Ser Leu Asn Glu Asp Tyr Ile Tyr Gly
245 250 255
Glu Cys Tyr Tyr Lys Ser Thr Asn Gly Thr Leu Phe Pro Leu Lys Val
260 265 270
Thr Val Thr Leu Asn Arg Arg Met Ser Ala Ser Gly Met Ala Tyr Ala
275 280 285
Met Asn Phe Ser Trp Ser Leu Asn Ala Glu Glu Ala Pro Glu Thr Thr
290 295 300
Glu Val Thr Leu Ile Thr Ser Pro Phe Phe Phe Ser Tyr Ile Arg Glu
305 310 315 320
Asp Asp
<210> 86
<211> 425
<212> PRT
<213> 黑猩猩腺病毒- CV68纤维
<400> 86
Met Ser Lys Lys Arg Val Arg Val Asp Asp Asp Phe Asp Pro Val Tyr
1 5 10 15
Pro Tyr Asp Ala Asp Asn Ala Pro Thr Val Pro Phe Ile Asn Pro Pro
20 25 30
Phe Val Ser Ser Asp Gly Phe Gln Glu Lys Pro Leu Gly Val Leu Ser
35 40 45
Leu Arg Leu Ala Asp Pro Val Thr Thr Lys Asn Gly Glu Ile Thr Leu
50 55 60
Lys Leu Gly Glu Gly Val Asp Leu Asp Ser Ser Gly Lys Leu Ile Ser
65 70 75 80
Asn Thr Ala Thr Lys Ala Ala Ala Pro Leu Ser Phe Ser Asn Asn Thr
85 90 95
Ile Ser Leu Asn Met Asp His Pro Phe Tyr Thr Lys Asp Gly Lys Leu
100 105 110
Ser Leu Gln Val Ser Pro Pro Leu Asn Ile Leu Arg Thr Ser Ile Leu
115 120 125
Asn Thr Leu Ala Leu Gly Phe Gly Ser Gly Leu Gly Leu Arg Gly Ser
130 135 140
Ala Leu Ala Val Gln Leu Val Ser Pro Leu Thr Phe Asp Thr Asp Gly
145 150 155 160
Asn Ile Lys Leu Thr Leu Asp Arg Gly Leu His Val Thr Thr Gly Asp
165 170 175
Ala Ile Glu Ser Asn Ile Ser Trp Ala Lys Gly Leu Lys Phe Glu Asp
180 185 190
Gly Ala Ile Ala Thr Asn Ile Gly Asn Gly Leu Glu Phe Gly Ser Ser
195 200 205
Ser Thr Glu Thr Gly Val Asp Asp Ala Tyr Pro Ile Gln Val Lys Leu
210 215 220
Gly Ser Gly Leu Ser Phe Asp Ser Thr Gly Ala Ile Met Ala Gly Asn
225 230 235 240
Lys Glu Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
245 250 255
Asn Cys Gln Ile Leu Ala Glu Asn Asp Ala Lys Leu Thr Leu Cys Leu
260 265 270
Thr Lys Cys Gly Ser Gln Ile Leu Ala Thr Val Ser Val Leu Val Val
275 280 285
Gly Ser Gly Asn Leu Asn Pro Ile Thr Gly Thr Val Ser Ser Ala Gln
290 295 300
Val Phe Leu Arg Phe Asp Ala Asn Gly Val Leu Leu Thr Glu His Ser
305 310 315 320
Thr Leu Lys Lys Tyr Trp Gly Tyr Arg Gln Gly Asp Ser Ile Asp Gly
325 330 335
Thr Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Lys Ala Tyr
340 345 350
Pro Lys Ser Gln Ser Ser Thr Thr Lys Asn Asn Ile Val Gly Gln Val
355 360 365
Tyr Met Asn Gly Asp Val Ser Lys Pro Met Leu Leu Thr Ile Thr Leu
370 375 380
Asn Gly Thr Asp Asp Ser Asn Ser Thr Tyr Ser Met Ser Phe Ser Tyr
385 390 395 400
Thr Trp Thr Asn Gly Ser Tyr Val Gly Ala Thr Phe Gly Ala Asn Ser
405 410 415
Tyr Thr Phe Ser Tyr Ile Ala Gln Glu
420 425
<210> 87
<211> 954
<212> PRT
<213> 黑猩猩腺病毒- ChAd20六邻体
<400> 87
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Pro Cys Glu Trp Asp Glu Ala Ala Thr Ala Leu Asp Ile
130 135 140
Asp Leu Asn Ala Glu Asp Asp Glu Glu Ser Asp Glu Ala Gln Gly Glu
145 150 155 160
Ala Asp Gln Gln Lys Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly
165 170 175
Gln Asn Ile Thr Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Ala Ser
180 185 190
Gln Ala Gln Thr Pro Val Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro
195 200 205
Gln Val Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser Tyr Gly Ala
210 215 220
Gly Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu Glu
245 250 255
Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe Ser Thr
260 265 270
Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro Lys Val Val
275 280 285
Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp Thr His Ile Ser
290 295 300
Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg Glu Leu Leu Gly Gln
305 310 315 320
Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
325 330 335
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
340 345 350
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
355 360 365
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr
370 375 380
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
385 390 395 400
Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr
405 410 415
Cys Phe Pro Leu Gly Gly Val Ile Asn Thr Glu Thr Phe Thr Lys Val
420 425 430
Lys Pro Lys Ala Ala Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe
435 440 445
Ser Asp Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile
450 455 460
Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala
465 470 475 480
Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln Ile
485 490 495
Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val Val Ala
500 505 510
Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu
515 520 525
Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly
530 535 540
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe
545 550 555 560
His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu
565 570 575
Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn
580 585 590
Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala
595 600 605
Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met
610 615 620
Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr
625 630 635 640
Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr
645 650 655
Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg
660 665 670
Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys
675 680 685
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser
690 695 700
Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
705 710 715 720
Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn
725 730 735
Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser Val Asp
740 745 750
Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
755 760 765
Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr
770 775 780
Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe
785 790 795 800
Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr
805 810 815
Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly
820 825 830
Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe
835 840 845
Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys
850 855 860
Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn
865 870 875 880
Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln Asn Leu Leu Tyr
885 890 895
Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met
900 905 910
Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val
915 920 925
Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg
930 935 940
Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950
<210> 88
<211> 940
<212> PRT
<213> 黑猩猩腺病毒- ChAd 4六邻体
<400> 88
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Ala
130 135 140
Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly
145 150 155 160
Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys
165 170 175
Asp Asp Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro
180 185 190
Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly
195 200 205
Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe
210 215 220
Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp
225 230 235 240
Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro
245 250 255
Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met
260 265 270
Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile
275 280 285
Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys Val Asn Leu Cys
290 295 300
Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn
305 310 315 320
Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu
325 330 335
Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg
340 345 350
Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg
355 360 365
Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro
370 375 380
Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn
385 390 395 400
Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly
405 410 415
Val Lys Pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser
420 425 430
Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met
435 440 445
Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn
450 455 460
Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile
465 470 475 480
Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val
485 490 495
Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp
500 505 510
Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn
515 520 525
Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val
530 535 540
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu
545 550 555 560
Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp
565 570 575
Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp
580 585 590
Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe
595 600 605
Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
610 615 620
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
625 630 635 640
Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro
645 650 655
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys
660 665 670
Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val
675 680 685
Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
690 695 700
Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro
705 710 715 720
Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr
725 730 735
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp
740 745 750
Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly
755 760 765
Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg
770 775 780
Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys
785 790 795 800
Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe
805 810 815
Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala
820 825 830
Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr
835 840 845
Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser
850 855 860
Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met
865 870 875 880
Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp
885 890 895
Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp
900 905 910
Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr
915 920 925
Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935 940
<210> 89
<211> 940
<212> PRT
<213> 黑猩猩腺病毒- ChAd 5六邻体
<400> 89
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Ala
130 135 140
Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly
145 150 155 160
Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys
165 170 175
Asp Asp Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro
180 185 190
Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly
195 200 205
Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe
210 215 220
Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp
225 230 235 240
Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro
245 250 255
Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met
260 265 270
Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile
275 280 285
Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys Val Asn Leu Cys
290 295 300
Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn
305 310 315 320
Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu
325 330 335
Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg
340 345 350
Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg
355 360 365
Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro
370 375 380
Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn
385 390 395 400
Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly
405 410 415
Val Lys Pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser
420 425 430
Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met
435 440 445
Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn
450 455 460
Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile
465 470 475 480
Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val
485 490 495
Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp
500 505 510
Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn
515 520 525
Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val
530 535 540
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu
545 550 555 560
Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp
565 570 575
Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp
580 585 590
Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe
595 600 605
Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
610 615 620
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
625 630 635 640
Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro
645 650 655
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys
660 665 670
Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val
675 680 685
Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
690 695 700
Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro
705 710 715 720
Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr
725 730 735
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp
740 745 750
Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly
755 760 765
Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg
770 775 780
Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys
785 790 795 800
Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe
805 810 815
Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala
820 825 830
Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val Thr
835 840 845
Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser
850 855 860
Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met
865 870 875 880
Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp
885 890 895
Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp
900 905 910
Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr
915 920 925
Leu Arg Thr Pro Phe Ser Ala Gly Lys Ala Thr Thr
930 935 940
<210> 90
<211> 940
<212> PRT
<213> 黑猩猩腺病毒- ChAd 7六邻体
<400> 90
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Lys Asn Ala
130 135 140
Asn Gly Asp Thr Glu Asn Val Thr Tyr Gly Val Ala Ala Met Gly Gly
145 150 155 160
Ile Asp Ile Asp Lys Asn Gly Leu Gln Ile Gly Thr Asp Asp Thr Lys
165 170 175
Asp Gly Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro
180 185 190
Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Tyr Ser Tyr Tyr Gly Gly
195 200 205
Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe
210 215 220
Ala Arg Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Ile Lys Thr Asp
225 230 235 240
Gly Asp Val Lys Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro
245 250 255
Asn Ser Gly Ala Gly Asn Gly Thr Asn Val Asn Asp Asp Pro Asp Met
260 265 270
Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile
275 280 285
Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Glu Val Asn Leu Cys
290 295 300
Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn
305 310 315 320
Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu
325 330 335
Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg
340 345 350
Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg
355 360 365
Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro
370 375 380
Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn
385 390 395 400
Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ser Val Tyr Gln Gly
405 410 415
Val Lys Pro Lys Thr Asp Asn Gly Asn Asp Gln Trp Glu Thr Asp Ser
420 425 430
Thr Val Ser Ser His Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met
435 440 445
Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn
450 455 460
Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile
465 470 475 480
Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val
485 490 495
Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp
500 505 510
Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn
515 520 525
Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val
530 535 540
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu
545 550 555 560
Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp
565 570 575
Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp
580 585 590
Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe
595 600 605
Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
610 615 620
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
625 630 635 640
Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro
645 650 655
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys
660 665 670
Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val
675 680 685
Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
690 695 700
Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro
705 710 715 720
Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr
725 730 735
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp
740 745 750
Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly
755 760 765
Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg
770 775 780
Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys
785 790 795 800
Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe
805 810 815
Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala
820 825 830
Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr
835 840 845
Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser
850 855 860
Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met
865 870 875 880
Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp
885 890 895
Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp
900 905 910
Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr
915 920 925
Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935 940
<210> 91
<211> 930
<212> PRT
<213> 黑猩猩腺病毒- ChAd 9六邻体
<400> 91
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Thr Tyr Thr Asp Asn Gln Thr Glu Lys
130 135 140
Thr Ala Thr Tyr Gly Asn Ala Pro Val Glu Gly Ile Asn Ile Thr Lys
145 150 155 160
Asp Gly Ile Gln Leu Gly Thr Asp Ser Asp Gly Gln Ala Ile Tyr Ala
165 170 175
Asp Glu Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Pro Glu Trp His
180 185 190
Asp Thr Thr Gly Thr Glu Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro
195 200 205
Ala Thr Asp Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn
210 215 220
Val Lys Gly Gly Gln Ala Lys Ser Arg Thr Lys Thr Asp Gly Thr Thr
225 230 235 240
Glu Pro Asp Ile Asp Met Ala Phe Phe Asp Gly Arg Asn Ala Thr Thr
245 250 255
Ala Gly Leu Thr Pro Glu Ile Val Leu Tyr Thr Glu Asn Val Asp Leu
260 265 270
Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp Asp Ser
275 280 285
Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn
290 295 300
Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser
305 310 315 320
Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala
325 330 335
Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu
340 345 350
Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln
355 360 365
Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly
370 375 380
Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Ala Val Gly
385 390 395 400
Arg Thr Asn Ser Tyr Gln Gly Ile Lys Pro Asn Gly Gly Asp Pro Ala
405 410 415
Thr Trp Ala Lys Asp Glu Ser Val Asn Asp Ser Asn Glu Leu Gly Lys
420 425 430
Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg
435 440 445
Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys
450 455 460
Tyr Thr Pro Ala Asn Ile Thr Leu Pro Ala Asn Thr Asn Thr Tyr Asp
465 470 475 480
Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile
485 490 495
Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro
500 505 510
Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu
515 520 525
Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe
530 535 540
Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu
545 550 555 560
Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly
565 570 575
Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn
580 585 590
Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu
595 600 605
Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr
610 615 620
Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn
625 630 635 640
Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp
645 650 655
Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly
660 665 670
Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly
675 680 685
Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp
690 695 700
Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu
705 710 715 720
Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln
725 730 735
Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr
740 745 750
Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg
755 760 765
Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val
770 775 780
Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln
785 790 795 800
His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln
805 810 815
Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser
820 825 830
Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met
835 840 845
Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr
850 855 860
Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp
865 870 875 880
Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val
885 890 895
Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly
900 905 910
Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala
915 920 925
Thr Thr
930
<210> 92
<211> 930
<212> PRT
<213> 黑猩猩腺病毒- ChAd 10六邻体
<400> 92
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Thr Tyr Thr Asp Asn Gln Thr Glu Lys
130 135 140
Thr Ala Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser Ile Thr Lys
145 150 155 160
Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro Ile Tyr Ala
165 170 175
Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala Glu Trp His
180 185 190
Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro
195 200 205
Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn
210 215 220
Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly Gly Thr Lys
225 230 235 240
Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser Ala Ala Ala
245 250 255
Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn Val Asp Leu
260 265 270
Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp Asp Ser
275 280 285
Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn
290 295 300
Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser
305 310 315 320
Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala
325 330 335
Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu
340 345 350
Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln
355 360 365
Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly
370 375 380
Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Ala Val Gly
385 390 395 400
Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Ala Asp Gln Thr
405 410 415
Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu Leu Gly Lys
420 425 430
Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg
435 440 445
Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys
450 455 460
Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp
465 470 475 480
Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile
485 490 495
Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro
500 505 510
Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu
515 520 525
Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe
530 535 540
Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu
545 550 555 560
Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly
565 570 575
Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn
580 585 590
Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu
595 600 605
Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr
610 615 620
Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn
625 630 635 640
Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp
645 650 655
Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly
660 665 670
Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly
675 680 685
Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp
690 695 700
Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu
705 710 715 720
Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln
725 730 735
Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr
740 745 750
Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg
755 760 765
Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val
770 775 780
Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln
785 790 795 800
His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln
805 810 815
Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser
820 825 830
Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met
835 840 845
Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr
850 855 860
Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp
865 870 875 880
Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val
885 890 895
Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly
900 905 910
Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala
915 920 925
Thr Thr
930
<210> 93
<211> 960
<212> PRT
<213> 黑猩猩腺病毒- ChAd 11六邻体
<400> 93
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135 140
Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu
145 150 155 160
Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu
165 170 175
Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala
180 185 190
Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro
195 200 205
Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val
210 215 220
Ala Gly Gly Arg Val Leu Lys Lys Thr Thr Pro Met Lys Pro Cys Tyr
225 230 235 240
Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu
245 250 255
Ala Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe
260 265 270
Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Ala Asn Asn Ile Gln Pro
275 280 285
Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr
290 295 300
His Leu Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Val Met
305 310 315 320
Leu Gly Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
325 330 335
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
340 345 350
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
355 360 365
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly
370 375 380
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
385 390 395 400
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu
405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr
420 425 430
Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp
435 440 445
Thr Lys Asp Glu Thr Phe Ala Glu Arg Asn Glu Ile Gly Val Gly Asn
450 455 460
Asn Phe Ala Met Glu Ile Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe
465 470 475 480
Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn
485 490 495
Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met
500 505 510
Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu
515 520 525
Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn
530 535 540
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn
545 550 555 560
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
565 570 575
Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn
580 585 590
Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp
595 600 605
Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr
610 615 620
Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala
625 630 635 640
Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser
645 650 655
Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro
660 665 670
Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe
675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
690 695 700
Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe
705 710 715 720
Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser
725 730 735
Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu
740 745 750
Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn
755 760 765
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile
770 775 780
Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr
785 790 795 800
Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln
805 810 815
Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn
820 825 830
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln
835 840 845
Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val
850 855 860
Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg
865 870 875 880
Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu
885 890 895
Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr
900 905 910
Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe
915 920 925
Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
930 935 940
Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955 960
<210> 94
<211> 944
<212> PRT
<213> 黑猩猩腺病毒- ChAd 16六邻体
<400> 94
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Thr Glu Asn Gly Gly Gly Gln
130 135 140
Ala Thr Thr Lys Thr His Thr Tyr Gly Val Ala Pro Met Gly Gly Thr
145 150 155 160
Asn Ile Thr Val Asp Gly Leu Gln Ile Gly Thr Asp Ala Thr Ala Asp
165 170 175
Thr Glu Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln
180 185 190
Ile Gly Glu Glu Asn Trp Gln Glu Thr Glu Ser Phe Tyr Gly Gly Arg
195 200 205
Ala Leu Lys Lys Asp Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala
210 215 220
Arg Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Leu Lys Val Gly Ala
225 230 235 240
Asp Gly Leu Pro Thr Lys Glu Phe Asp Ile Asp Leu Ala Phe Phe Asp
245 250 255
Thr Pro Gly Gly Thr Val Thr Gly Gly Thr Glu Glu Tyr Lys Ala Asp
260 265 270
Ile Val Met Tyr Thr Glu Asn Thr Tyr Leu Glu Thr Pro Asp Thr His
275 280 285
Val Val Tyr Lys Pro Gly Lys Asp Asn Thr Ser Ser Lys Ile Asn Leu
290 295 300
Val Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp
305 310 315 320
Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val
325 330 335
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp
340 345 350
Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp
355 360 365
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp
370 375 380
Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro
385 390 395 400
Asn Tyr Cys Phe Pro Leu Asp Gly Ser Gly Thr Asn Ala Ala Tyr Gln
405 410 415
Gly Val Lys Val Lys Asn Gly Gln Asp Gly Asp Val Glu Ser Glu Trp
420 425 430
Glu Lys Asp Asp Thr Val Ala Ala Arg Asn Gln Leu Cys Lys Gly Asn
435 440 445
Ile Phe Ala Met Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe
450 455 460
Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr
465 470 475 480
Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met
485 490 495
Asn Gly Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile
500 505 510
Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn
515 520 525
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn
530 535 540
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
545 550 555 560
Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn
565 570 575
Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp
580 585 590
Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr
595 600 605
Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala
610 615 620
Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser
625 630 635 640
Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro
645 650 655
Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe
660 665 670
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
675 680 685
Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe
690 695 700
Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser
705 710 715 720
Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu
725 730 735
Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn
740 745 750
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile
755 760 765
Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr
770 775 780
Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu
785 790 795 800
Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn
805 810 815
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln
820 825 830
Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val
835 840 845
Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg
850 855 860
Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu
865 870 875 880
Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn
885 890 895
Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe
900 905 910
Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
915 920 925
Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935 940
<210> 95
<211> 960
<212> PRT
<213> 黑猩猩腺病毒- ChAd 17六邻体
<400> 95
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135 140
Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu
145 150 155 160
Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu
165 170 175
Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala
180 185 190
Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro
195 200 205
Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val
210 215 220
Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr
225 230 235 240
Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu
245 250 255
Thr Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe
260 265 270
Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Thr Asn Asn Ile Gln Pro
275 280 285
Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr
290 295 300
His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile Met
305 310 315 320
Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
325 330 335
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
340 345 350
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
355 360 365
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly
370 375 380
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
385 390 395 400
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu
405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr
420 425 430
Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp
435 440 445
Thr Lys Asp Glu Thr Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn
450 455 460
Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe
465 470 475 480
Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn
485 490 495
Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met
500 505 510
Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu
515 520 525
Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn
530 535 540
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn
545 550 555 560
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
565 570 575
Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn
580 585 590
Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp
595 600 605
Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr
610 615 620
Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala
625 630 635 640
Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser
645 650 655
Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro
660 665 670
Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe
675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
690 695 700
Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe
705 710 715 720
Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser
725 730 735
Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu
740 745 750
Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn
755 760 765
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile
770 775 780
Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr
785 790 795 800
Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln
805 810 815
Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn
820 825 830
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln
835 840 845
Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val
850 855 860
Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg
865 870 875 880
Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu
885 890 895
Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr
900 905 910
Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe
915 920 925
Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
930 935 940
Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955 960
<210> 96
<211> 958
<212> PRT
<213> 黑猩猩腺病毒- ChAd 19六邻体
<400> 96
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala
130 135 140
Leu Glu Asp Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu
145 150 155 160
Ala Pro Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly
165 170 175
Glu Glu Ile Thr Lys Asp Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu
180 185 190
Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro
195 200 205
Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly
210 215 220
Gly Arg Val Leu Lys Lys Thr Thr Pro Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu Val Ala
245 250 255
Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu Leu Gln Phe Phe Ser
260 265 270
Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly Asn Asp Thr Lys Pro Lys
275 280 285
Val Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr His
290 295 300
Ile Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Val Met Leu
305 310 315 320
Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp
325 330 335
Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val
340 345 350
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp
355 360 365
Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp
370 375 380
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp
385 390 395 400
Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro
405 410 415
Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln
420 425 430
Val Ile Lys Thr Asn Gly Asn Gly Gln Ala Asp Pro Thr Trp Glu Lys
435 440 445
Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe
450 455 460
Ala Met Glu Ile Asn Leu Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr
465 470 475 480
Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser
485 490 495
Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys
500 505 510
Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala
515 520 525
Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His
530 535 540
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg
545 550 555 560
Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys
565 570 575
Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg
580 585 590
Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg
595 600 605
Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr
610 615 620
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu
625 630 635 640
Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala
645 650 655
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
660 665 670
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg
675 680 685
Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr
690 695 700
Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu
705 710 715 720
Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser
725 730 735
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
740 745 750
Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr
755 760 765
Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr
770 775 780
Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe
785 790 795 800
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys
805 810 815
Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser
820 825 830
Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr
835 840 845
Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser
850 855 860
Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro
865 870 875 880
Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln
885 890 895
Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu
900 905 910
Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val
915 920 925
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr
930 935 940
Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955
<210> 97
<211> 2865
<212> DNA
<213> 黑猩猩腺病毒- ChAd 8六邻体
<400> 97
atggccaccc catcgatgtt gccccagtgg gcatacatgc acatcgccgg acaggatgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120
ctggggaaca agtttaggaa ccccaccgtg gcccccaccc acgatgtgac caccgaccga 180
agccagcggc tgatgctgcg ctttgtgccc gttgatcggg aggacaatac ctactcatac 240
aaagttcgct acacactggc tgtgggcgac aacagagtgc tggatatggc cagcaccttc 300
tttgacatcc ggggggtgct tgacagaggt cccagtttca agccatactc tggcacggct 360
tacaactcct tggctcctaa gggtgccccc aatacatgcc agtggatagc taaagggtcg 420
cccgttcaag atgatgctga acaagctcag gaacaaaaag atgttaccta tacttttggc 480
aatgcgccag taaaagcaga agatgacatt acaaaagacg gattagaagt aggcatacaa 540
attattggtg atgaggagaa tcccatttat gcagataaaa catatcaacc agagccacag 600
gttggtgacg agcaatggca tgacacaact ggaaccactg agcagtatgg aggcagagct 660
cttaagccag ctacaaacat gaggccatgc tatggctctt ttgccagacc tacaaacaaa 720
aaaggagggc aagctaaaac cagaaaagta gaaaaaactg aaggtgacaa aaagactgaa 780
gttgaagaac ttgacattga tatggatttt tatgatgcaa gatctaaaaa acaaggctat 840
gatcctcaaa tagtgctata ttcagaaaat gtaaatctgg aaacgcccga cactcatatt 900
gtgtacaaac cgggaactga tgaaaccagt tcctccacta atttgggcca gcaagctatg 960
cccaacagac ccaattacat tggtttcagg gacaacttca ttggacttat gtattataac 1020
agtactggta acatgggagt gctggccggt caagcttctc agttgaatgc tgtggtcgac 1080
ttgcaggaca ggaacacaga actgtcctac cagctgctgc ttgactctct gggtgacaga 1140
accagatact ttagcatgtg gaatcaggcc gtggatagct atgacccaga tgtgcgcatt 1200
attgaaaatc atggtgtgga agatgaactt cccaattatt gtttcccatt ggatggtgtt 1260
ggtccaatta cagaaaccta tcaaggtatc aagccaaaaa cagcagacaa tgcaaatgac 1320
caatgggaaa aaaataccga agtaaatgga gctaatgaaa taggaaaggg aaacaattat 1380
gcaatggaaa ttaatctaca agctaacctc tggagaagtt ttctttactc caacgtggct 1440
ctgtatcttc cagacggtta caaatatacc ccagccaatg ttacgctgcc agacaacaaa 1500
aatacctatg ggtacataaa cggacgagta gtgtctccat ctttggtgga ttcatacatc 1560
aacattggag ccagatggtc tttggatctt atggacaatg tcaacccatt taatcaccac 1620
cgcaatgctg ggctgcgcta ccgttccatg cttcttggca atggacgcta tgtgcccttc 1680
cacatccaag tgccgcagaa attctttgct atcaagaact tgctgcttct gccaggctcc 1740
tacacctatg agtggaactt cagaaaggat gtgaacatgg tcctacaaag ttcccttggt 1800
aatgatctca gaactgatgg agccagcatc agttttacca gcatcaacct ctatgccacc 1860
tttttcccaa tggctcacaa cactgcttcc acccttgaag ccatgctgcg caatgacacc 1920
aatgaccagt cattcaacga ctacctctct gcagccaaca tgctctaccc catccctgcc 1980
aatgccacta acattcccat ctccattccc tctcgcaact gggctgcctt caggggctgg 2040
tccttcacca gactcaaaac caaggagact ccctctttgg gatcagggtt cgatccctac 2100
tttgtctatt caggctccat tccctacctg gatggtacct tctacctcaa ccacactttc 2160
aagaaggtct ccatcatgtt tgactcctca gtcagctggc cgggcaatga cagactgttg 2220
tgtcccaatg agtttgaaat caagcgcact gtggatgggg aagggtacaa cgtggctcaa 2280
tgcaacatga ccaaggattg gttcttggtc cagatgcttg ccaactacaa cattggctac 2340
cagggcttct acatcccaga ggggtacaag gatcgcatgt actccttctt cagaaacttc 2400
cagcccatga gcagacaggt agttgatgaa gtcaattaca aggagtacca agctgtcaca 2460
cttgcttacc agcacaacaa ctctggtttt gtgggttacc atgcacccac tcttcgtcag 2520
ggccaaccat acccagctaa ctacccctac ccgctcattg gaaccactgc tgtcaccagc 2580
gtcacccaga aaaagttctt gtgcgacagg accatgtggc gcatcccatt ctccagcaac 2640
ttcatgtcca tgggtgccct taccgacctg gggcagaaca tgctttatgc caactcagcc 2700
catgcgctgg acatgacttt tgaggtggat cccatggatg agcccacact gctttatctt 2760
ctttttgaag tcttcgacgt ggtcagagtg caccagccac accgcggcgt catcgaggct 2820
gtctacctgc gtaccccatt ctcagctggt aacgccacca cataa 2865
<210> 98
<211> 954
<212> PRT
<213> 黑猩猩腺病毒 ChAd 8
<400> 98
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Ile Ala Lys Gly Ser Pro Val Gln Asp
130 135 140
Asp Ala Glu Gln Ala Gln Glu Gln Lys Asp Val Thr Tyr Thr Phe Gly
145 150 155 160
Asn Ala Pro Val Lys Ala Glu Asp Asp Ile Thr Lys Asp Gly Leu Glu
165 170 175
Val Gly Ile Gln Ile Ile Gly Asp Glu Glu Asn Pro Ile Tyr Ala Asp
180 185 190
Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Glu Gln Trp His Asp
195 200 205
Thr Thr Gly Thr Thr Glu Gln Tyr Gly Gly Arg Ala Leu Lys Pro Ala
210 215 220
Thr Asn Met Arg Pro Cys Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys
225 230 235 240
Lys Gly Gly Gln Ala Lys Thr Arg Lys Val Glu Lys Thr Glu Gly Asp
245 250 255
Lys Lys Thr Glu Val Glu Glu Leu Asp Ile Asp Met Asp Phe Tyr Asp
260 265 270
Ala Arg Ser Lys Lys Gln Gly Tyr Asp Pro Gln Ile Val Leu Tyr Ser
275 280 285
Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Pro
290 295 300
Gly Thr Asp Glu Thr Ser Ser Ser Thr Asn Leu Gly Gln Gln Ala Met
305 310 315 320
Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu
325 330 335
Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala
340 345 350
Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu
355 360 365
Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe
370 375 380
Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile
385 390 395 400
Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro
405 410 415
Leu Asp Gly Val Gly Pro Ile Thr Glu Thr Tyr Gln Gly Ile Lys Pro
420 425 430
Lys Thr Ala Asp Asn Ala Asn Asp Gln Trp Glu Lys Asn Thr Glu Val
435 440 445
Asn Gly Ala Asn Glu Ile Gly Lys Gly Asn Asn Tyr Ala Met Glu Ile
450 455 460
Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala
465 470 475 480
Leu Tyr Leu Pro Asp Gly Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu
485 490 495
Pro Asp Asn Lys Asn Thr Tyr Gly Tyr Ile Asn Gly Arg Val Val Ser
500 505 510
Pro Ser Leu Val Asp Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu
515 520 525
Asp Leu Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly
530 535 540
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe
545 550 555 560
His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu
565 570 575
Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn
580 585 590
Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala
595 600 605
Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met
610 615 620
Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr
625 630 635 640
Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr
645 650 655
Pro Ile Pro Ala Asn Ala Thr Asn Ile Pro Ile Ser Ile Pro Ser Arg
660 665 670
Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys
675 680 685
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser
690 695 700
Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
705 710 715 720
Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro Gly Asn
725 730 735
Asp Arg Leu Leu Cys Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp
740 745 750
Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
755 760 765
Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr
770 775 780
Ile Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe
785 790 795 800
Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Glu Tyr
805 810 815
Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly
820 825 830
Tyr His Ala Pro Thr Leu Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr
835 840 845
Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr Gln Lys
850 855 860
Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser Ser Asn
865 870 875 880
Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr
885 890 895
Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met
900 905 910
Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp Val Val
915 920 925
Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg
930 935 940
Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950
<210> 99
<211> 2871
<212> DNA
<213> 黑猩猩腺病毒- ChAd 22六邻体
<400> 99
atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcaat 120
ctggggaaca agtttaggaa ccctaccgtg gcgcccaccc atgatgtgac caccgaccgc 180
agtcaacggc tgatgctccg ctttgtgccc gttgaccggg aggacaatac ctactcatac 240
aaagttcgat acaccttggc tgtgggcgac aacagagtgc tggatatggc cagtactttc 300
tttgacattc ggggtgtgtt ggatagaggc cctagcttca agccatattc tggcactgct 360
tacaactcat tggcccctaa gggcgctccc aatacatctc agtggattgc tgaaggcgta 420
aaaaaagaaa atggggaagc tgacaatgaa gcagctgtcg aagaggaaga ggaagagaaa 480
aatcttacca cttacacttt tggaaatgcc ccagtgaaag cagaaggtgg tgatatcact 540
aaagacaaag gtcttccaat tggttcagaa attacagacg gcgaagccaa accaatttat 600
gcagataaac tataccaacc agaacctcag gtgggagagg aaacttggac tgacacagat 660
ggaacaactg agaagtatgg tggtagagct ctaaagccag aaactaaaat gaaaccctgc 720
tatgggtctt ttgctaaacc cactaacgtc aaaggcggac aggcaaaaca aaaaactact 780
gaacaactgc aaaaccagca ggttgaatat gatattgaca tgaacttttt tgatcaagcg 840
tcacagaaag caaacttcag tccaaaaatt gtgatgtatg cagaaaatgt agacttggaa 900
accccagaca ctcacgtggt gtacaaacct ggtacttcag aagaaagttc tcatgctaat 960
ctcggtcaac aatctatgcc caacagaccc aactacattg gctttagaga taactttatt 1020
ggacttatgt actacaacag tactggcaac atgggagtgc tggcaggtca agcatcccaa 1080
ttgaatgcgg tggttgactt gcaggacaga aacacagaac tatcatatca actactgctt 1140
gattctctgg gtgacagaac cagatacttc agcatgtgga atcaagcagt cgatagctat 1200
gatcctgatg tgcgcattat tgaaaatcat ggggtggaag atgagcttcc caactactgc 1260
tttccattgg atggagtagg ggtaccaaca actagttaca aaataattga accaaatgga 1320
gagggtgcag attggaaaga gcctgacata aatggaacaa gtgaaattgg acaaggaaat 1380
ctctttgcca tggaaattaa cctccaagct aatctctgga gaagttttct ttattccaat 1440
gtggctctgt atctcccaga ctcctacaaa tacaccccag ccaatgtcac tcttccaact 1500
aacaccaaca cttatgacta catgaatggg cgggtggttc ccccatccct agtggatacc 1560
tacgtaaaca ttggcgccag atggtctttg gatgccatgg acaatgtcaa cccctttaac 1620
catcaccgca acgctggcct gcgataccgg tccatgcttt tgggcaatgg tcgctacgtg 1680
cctttccaca ttcaagtgcc tcagaaattc tttgctgtga agaacctgct gcttctaccc 1740
ggttcttaca cctacgagtg gaacttcaga aaggatgtga acatggtcct gcagagttcc 1800
cttggtaatg atctccgggt cgatggtgcc agcatcagtt ttaccagcat caatctctat 1860
gccaccttct tccccatggc ccacaacact gcctccaccc ttgaagccat gctgcgcaat 1920
gacaccaatg atcaatcatt caatgactac ctttctgcag ccaacatgct ctaccccatc 1980
ccggccaacg ctaccaacgt tcccatctcc attccctctc gtaactgggc cgccttcaga 2040
ggctggtcct tcaccagact caaaaccaaa gagactccct ctttgggatc agggttcgat 2100
ccctactttg tttactctgg ttctatacct tacctggatg gtaccttcta ccttaaccac 2160
acttttaaga aagtctctat catgtttgac tcttcagtca gctggcctgg taatgacaga 2220
ttgctaactc caaatgagtt cgaaatcaag cgcacagttg atggggaagg ctacaatgtg 2280
gcccaatgta acatgaccaa agactggttc ctggtccaga tgcttgccaa ctacaacatt 2340
ggataccagg gcttctacgt tcctgagggt tacaaggatc gcatgtactc cttcttcaga 2400
aacttccagc ccatgagtag acaggtggtt gatgagatta actacaaaga ctataaagct 2460
gtcgccgtac cctaccagca taataactct ggctttgtgg gttacatggc tcctaccatg 2520
cgtcagggtc aagcgtaccc tgctaactac ccataccccc taattggaac cactgcagta 2580
accagtgtca cccagaaaaa attcctgtgc gacaggacca tgtggcgcat cccattctct 2640
agcaacttca tgtccatggg tgcccttaca gacctgggac agaacttgct gtatgccaac 2700
tcagcccatg cgctggacat gacttttgag gtggatccca tggatgagcc caccctgctt 2760
tatcttcttt ttgaagtatt cgacgtggtc agagtgcacc aaccacaccg cggcgtcatc 2820
gaggccgtct acctgcgcac accgttctcg gctggtaacg ccaccacata a 2871
<210> 100
<211> 956
<212> PRT
<213> 黑猩猩腺病毒- ChAd 22六邻体
<400> 100
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Ser Gln Trp Ile Ala Glu Gly Val Lys Lys Glu Asn
130 135 140
Gly Glu Ala Asp Asn Glu Ala Ala Val Glu Glu Glu Glu Glu Glu Lys
145 150 155 160
Asn Leu Thr Thr Tyr Thr Phe Gly Asn Ala Pro Val Lys Ala Glu Gly
165 170 175
Gly Asp Ile Thr Lys Asp Lys Gly Leu Pro Ile Gly Ser Glu Ile Thr
180 185 190
Asp Gly Glu Ala Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln Pro Glu
195 200 205
Pro Gln Val Gly Glu Glu Thr Trp Thr Asp Thr Asp Gly Thr Thr Glu
210 215 220
Lys Tyr Gly Gly Arg Ala Leu Lys Pro Glu Thr Lys Met Lys Pro Cys
225 230 235 240
Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val Lys Gly Gly Gln Ala Lys
245 250 255
Gln Lys Thr Thr Glu Gln Leu Gln Asn Gln Gln Val Glu Tyr Asp Ile
260 265 270
Asp Met Asn Phe Phe Asp Gln Ala Ser Gln Lys Ala Asn Phe Ser Pro
275 280 285
Lys Ile Val Met Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr
290 295 300
His Val Val Tyr Lys Pro Gly Thr Ser Glu Glu Ser Ser His Ala Asn
305 310 315 320
Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
325 330 335
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
340 345 350
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
355 360 365
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly
370 375 380
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
385 390 395 400
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu
405 410 415
Pro Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Val Pro Thr Thr Ser
420 425 430
Tyr Lys Ile Ile Glu Pro Asn Gly Glu Gly Ala Asp Trp Lys Glu Pro
435 440 445
Asp Ile Asn Gly Thr Ser Glu Ile Gly Gln Gly Asn Leu Phe Ala Met
450 455 460
Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn
465 470 475 480
Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Val
485 490 495
Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val
500 505 510
Val Pro Pro Ser Leu Val Asp Thr Tyr Val Asn Ile Gly Ala Arg Trp
515 520 525
Ser Leu Asp Ala Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn
530 535 540
Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val
545 550 555 560
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Val Lys Asn Leu
565 570 575
Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp
580 585 590
Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp
595 600 605
Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe
610 615 620
Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
625 630 635 640
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
645 650 655
Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro
660 665 670
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys
675 680 685
Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val
690 695 700
Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
705 710 715 720
Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro
725 730 735
Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr
740 745 750
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp
755 760 765
Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly
770 775 780
Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg
785 790 795 800
Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys
805 810 815
Asp Tyr Lys Ala Val Ala Val Pro Tyr Gln His Asn Asn Ser Gly Phe
820 825 830
Val Gly Tyr Met Ala Pro Thr Met Arg Gln Gly Gln Ala Tyr Pro Ala
835 840 845
Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr
850 855 860
Gln Lys Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser
865 870 875 880
Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu
885 890 895
Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp
900 905 910
Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp
915 920 925
Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr
930 935 940
Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955
<210> 101
<211> 2865
<212> DNA
<213> 黑猩猩腺病毒- ChAd 24六邻体
<400> 101
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tcccagcgcc tgacgctgcg gttcatcccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggcgtgct ggaccgcggc cccaccttca agccctactc cggcaccgcc 360
tacaactccc tggcccccaa gggcgcgccc aacccatgcg agtgggatga ggctgctact 420
gcccttgaca ttgatttgaa cgcagaagaa gatgaagaag gcgatgaagc ccaaggggaa 480
gcagatcagc agaaaactca tgtatttggc caggcgccat actccggaca gaacattaca 540
aaagaaggca tacagatagg cattgatgct accagtcaag cccaaacacc tctatatgcc 600
gacaaaacat tccaacccga acctcaggtt ggagaatcac aatggaatga gacagagatt 660
agccatggag cgggacgggt gctaaaaaag accactctca tgaaaccttg ctatgggtca 720
tatgcaaggc ctactaatga gaacggaggt cagggcatcc tcctggaaca agatggaaag 780
aaagaaagtc aagtggaaat gcaatttttc tccactactc aggcagctgc gggtaattca 840
gataatccta ctccaaagct tgttttgtac agcgaggatg ttaacctgga aacaccagat 900
acacacattt catacatgcc cactaacaac gaaaccaatt caagagaact gttgggacaa 960
caggccatgc ccaacaggcc taattacatc ggcttcagag acaactttat cggtctcatg 1020
tactacaaca gcactggcaa catgggagtg cttgcaggtc aggcctctca gttgaatgca 1080
gtggtggact tgcaagacag aaacacagaa ctgtcctacc agctcttgct tgattccatg 1140
ggtgacagaa ccagatattt ctccatgtgg aatcaggcag tggacagtta tgacccagat 1200
gtcagaatta ttgaaaatca tggaaccgaa gacgagctcc ccaactactg ttttcctctg 1260
ggtggcataa tcaatacgga aacttttaca aaagtcaagc ctaaagctgg acaggacgct 1320
cagtgggaaa aagattcaga attttcagat aaaaatgaaa taagagtggg aaacaacttc 1380
gctatggaaa tcaacatcaa tgccaacctg tggaggaact tcctgtactc caacgtggcc 1440
ctgtacctgc cagacaagct taagtatact ccatccaatg tgcaaatttc caacaacccc 1500
aactcctacg attacatgaa caagcgagtg gtggccccgg ggctggtgga ctgctacatc 1560
aacctgggcg cgcggtggtc gctggactac atggacaacg tcaacccctt caaccaccac 1620
cgcaacgcgg gcctgcgcta ccgctccatg ctcctgggca acgggcgcta cgtgcccttc 1680
cacatccagg tgccccagaa gttctttgcc atcaagaacc tcctcctcct gccgggctcc 1740
tacacctacg agtggaactt caggaaggat gtcaacatgg tcctccagag ctctctgggc 1800
aacgatctca gggtggacgg ggccagcatc aagttcgaga gcatctgcct ctacgccacc 1860
ttcttcccca tggcccacaa cacggcctcc acgctcgagg ccatgctcag gaacgacacc 1920
aacgaccagt ccttcaatga ctacctctcc gccgccaaca tgctctaccc catccccgcc 1980
aacgccacca acgtccccat ctccatcccc tcgcgcaact gggcggcctt ccgcggctgg 2040
gccttcaccc gcctcaagac caaggagacc ccctccctgg gctcgggatt cgacccctac 2100
tacacctact cgggatccat tccctacctg gacggcacct tctacctcaa ccacactttc 2160
aagaaggtct cggtcacctt cgactcctcg gtcagctggc cgggcaacga ccgcctgctc 2220
acccccaacg agttcgagat caagcgctcg gtcgacgggg agggctacaa cgtggcccag 2280
tgcaacatga ccaaggactg gttcctggtc cagatgctgg ccaactacaa catcggctac 2340
cagggcttct acatcccaga gagctacaag gacaggatgt actccttctt caggaacttc 2400
cagcccatga gccggcaggt ggtggaccag accaagtaca aggactacca ggaggtgggc 2460
atcatccacc agcacaacaa ctcgggcttc gtgggctacc tcgcccccac catgcgcgag 2520
ggacaggcct accccgccaa cttcccctac ccgctcatag gcaagaccgc ggtcgacagc 2580
atcacccaga aaaagttcct ctgcgaccgc accctctggc gcatcccctt ctccagcaac 2640
ttcatgtcca tgggtgcgct cacggacctg ggccagaacc tgctctatgc caactccgcc 2700
cacgcgctcg acatgacctt cgaggtcgac cccatggacg agcccaccct tctctatgtt 2760
ctgttcgaag tctttgacgt ggtccgggtc caccagccgc accgcggcgt catcgagacc 2820
gtgtacctgc gcacgccctt ctcggccggc aacgccacca cctaa 2865
<210> 102
<211> 954
<212> PRT
<213> 黑猩猩腺病毒- ChAd 24六邻体
<400> 102
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Pro Cys Glu Trp Asp Glu Ala Ala Thr Ala Leu Asp Ile
130 135 140
Asp Leu Asn Ala Glu Glu Asp Glu Glu Gly Asp Glu Ala Gln Gly Glu
145 150 155 160
Ala Asp Gln Gln Lys Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly
165 170 175
Gln Asn Ile Thr Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Thr Ser
180 185 190
Gln Ala Gln Thr Pro Leu Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro
195 200 205
Gln Val Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser His Gly Ala
210 215 220
Gly Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu Glu
245 250 255
Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe Ser Thr
260 265 270
Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro Lys Leu Val
275 280 285
Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp Thr His Ile Ser
290 295 300
Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg Glu Leu Leu Gly Gln
305 310 315 320
Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
325 330 335
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
340 345 350
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
355 360 365
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr
370 375 380
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
385 390 395 400
Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr
405 410 415
Cys Phe Pro Leu Gly Gly Ile Ile Asn Thr Glu Thr Phe Thr Lys Val
420 425 430
Lys Pro Lys Ala Gly Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe
435 440 445
Ser Asp Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile
450 455 460
Asn Ile Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala
465 470 475 480
Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln Ile
485 490 495
Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val Val Ala
500 505 510
Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu
515 520 525
Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly
530 535 540
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe
545 550 555 560
His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu
565 570 575
Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn
580 585 590
Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala
595 600 605
Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met
610 615 620
Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr
625 630 635 640
Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr
645 650 655
Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg
660 665 670
Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys
675 680 685
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser
690 695 700
Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
705 710 715 720
Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn
725 730 735
Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser Val Asp
740 745 750
Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
755 760 765
Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr
770 775 780
Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe
785 790 795 800
Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr
805 810 815
Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly
820 825 830
Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe
835 840 845
Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys
850 855 860
Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn
865 870 875 880
Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu Leu Tyr
885 890 895
Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met
900 905 910
Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val
915 920 925
Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg
930 935 940
Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950
<210> 103
<211> 2841
<212> DNA
<213> 黑猩猩腺病毒- ChAd 26六邻体
<400> 103
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggctcccaa gggagcaccc aattccagcc agtgggagca aaaaaagaca 420
ggcaataaca atggaaatgg cggcactgaa tctgttacct ttggtgtagc cgccatgggc 480
ggagagaata ttacaaaaga gggtcttcaa attggaagtg atgaaactaa aaccgataac 540
aaagaaattt atgcagacaa gacctaccaa cctgagcctc aaataggaga ggagaactgg 600
caagaaacat tctcttttta tggtggtaga gctcttaaaa aagatactaa gatgaaacca 660
tgctatggct cctttgctag gcccacaaat gaaaagggag gtcaggccaa atttaaagtt 720
caagacggtg tgcagactac agaatatgac atcgacctgg ctttctttga tattccaagc 780
accggcacag ggggcaatgg tacaaatgta aatgataagc cagacatggt catgtacact 840
gaaaatgtga atttggagac gccagatact catattgtgt acaaacctgg aacttcagat 900
gacagctcta aagccaactt gtgccagcag gccatgccaa acagacccaa ctacattggt 960
ttcagagaca actttattgg gctcatgtat tacaacagta ctggcaatat gggggtgctg 1020
gctggtcagg cctctcagct gaatgctgtg gtcgacttgc aagacagaaa caccgaactg 1080
tcttaccagc tcttgctcga ctctctgggt gacagaacca ggtatttcag tatgtggaac 1140
caggcggtgg acagttatga ccctgatgtg cgcattattg aaaaccatgg tgtggaggat 1200
gaattgccaa actattgctt ccccttggat ggagctggca ctaatgctgt ataccagggt 1260
gttaaagcaa aagataacgg aaacgcagcc aatggaaact gggaacaaga cacaggcgtt 1320
tcaagtatta accagatatg caaggggaac atctatgcca tggaaatcaa cattcaagcc 1380
aacctgtgga gaagtttcct ttactcgaac gtggccctgt acctgcccga ctcttacaag 1440
tacacgccgg ccaacatcac cctgcccacc aacaccaaca cctacgatta catgaacggt 1500
cgggtggtgc ctccctcgct ggtggacgcc tacatcaaca tcggggcgcg ctggtcgctg 1560
gaccccatgg acaacgtcaa tcccttcaac caccaccgca acgcgggcct gcgctaccgc 1620
tccatgctcc tgggcaacgg gcgctacgtg cccttccaca tccaggtgcc ccagaaattt 1680
ttcgccatca agagcctcct gctcctgccc gggtcctaca cctacgagtg gaacttccgc 1740
aaggacgtca acatgatcct gcagagctcc ctcggcaacg acctgcgcac ggacggggcc 1800
tccatctcct tcaccagcat caacctctac gccaccttct tccccatggc gcacaacacg 1860
gcttccacgc tcgaggccat gctgcgcaac gacaccaacg accagtcctt caacgactac 1920
ctctcggcgg ccaacatgct ctaccccatc ccggccaacg ccaccaacgt gcccatctcc 1980
atcccctcgc gcaactgggc cgccttccgc ggctggtcct tcacgcgtct caagaccaag 2040
gaaacgccct cgctgggctc cgggttcgac ccctacttcg tctactcggg ctccatcccc 2100
tacctcgacg gcaccttcta cctcaaccac accttcaaga aggtctccat caccttcgac 2160
tcctccgtca gctggcccgg caacgaccgg ctcctgacgc ccaacgagtt cgaaatcaag 2220
cgcaccgtcg acggcgaggg ctacaacgtg gcccagtgca acatgaccaa ggactggttc 2280
ctggtccaga tgctggccca ctacaacatc ggctaccagg gcttctacgt gcccgagggc 2340
tacaaggacc gcatgtactc cttcttccgc aacttccagc ccatgagccg ccaggtggtg 2400
gacgaggtca actacaagga ctaccaggcc gtcaccctgg cctaccagca caacaactcg 2460
ggcttcgtcg gctacctcgc gcccaccatg cgccagggcc agccctaccc cgccaactac 2520
ccctacccgc tcatcggcaa gagcgccgtc accagcgtca cccagaaaaa gttcctctgc 2580
gacagggtca tgtggcgcat ccccttctcc agcaacttca tgtccatggg cgcgctcacc 2640
gacctcggcc agaacatgct ctatgccaac tccgcccacg cgctagacat gaatttcgaa 2700
gtcgacccca tggatgagtc cacccttctc tatgttgtct tcgaagtctt cgacgtcgtc 2760
cgagtgcacc agccccaccg cggcgtcatc gaggccgtct acctgcgcac ccccttctcg 2820
gccggcaacg ccaccaccta a 2841
<210> 104
<211> 946
<212> PRT
<213> 黑猩猩腺病毒- ChAd 26六邻体
<400> 104
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Lys Lys Thr Gly Asn Asn Asn
130 135 140
Gly Asn Gly Gly Thr Glu Ser Val Thr Phe Gly Val Ala Ala Met Gly
145 150 155 160
Gly Glu Asn Ile Thr Lys Glu Gly Leu Gln Ile Gly Ser Asp Glu Thr
165 170 175
Lys Thr Asp Asn Lys Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu
180 185 190
Pro Gln Ile Gly Glu Glu Asn Trp Gln Glu Thr Phe Ser Phe Tyr Gly
195 200 205
Gly Arg Ala Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser
210 215 220
Phe Ala Arg Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Phe Lys Val
225 230 235 240
Gln Asp Gly Val Gln Thr Thr Glu Tyr Asp Ile Asp Leu Ala Phe Phe
245 250 255
Asp Ile Pro Ser Thr Gly Thr Gly Gly Asn Gly Thr Asn Val Asn Asp
260 265 270
Lys Pro Asp Met Val Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro
275 280 285
Asp Thr His Ile Val Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Lys
290 295 300
Ala Asn Leu Cys Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly
305 310 315 320
Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn
325 330 335
Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp
340 345 350
Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser
355 360 365
Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp
370 375 380
Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp
385 390 395 400
Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ala
405 410 415
Val Tyr Gln Gly Val Lys Ala Lys Asp Asn Gly Asn Ala Ala Asn Gly
420 425 430
Asn Trp Glu Gln Asp Thr Gly Val Ser Ser Ile Asn Gln Ile Cys Lys
435 440 445
Gly Asn Ile Tyr Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg
450 455 460
Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys
465 470 475 480
Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp
485 490 495
Tyr Met Asn Gly Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile
500 505 510
Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro
515 520 525
Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu
530 535 540
Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe
545 550 555 560
Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu
565 570 575
Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly
580 585 590
Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn
595 600 605
Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu
610 615 620
Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr
625 630 635 640
Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn
645 650 655
Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp
660 665 670
Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly
675 680 685
Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly
690 695 700
Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp
705 710 715 720
Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu
725 730 735
Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln
740 745 750
Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr
755 760 765
Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg
770 775 780
Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val
785 790 795 800
Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln
805 810 815
His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln
820 825 830
Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser
835 840 845
Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met
850 855 860
Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr
865 870 875 880
Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp
885 890 895
Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val
900 905 910
Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly
915 920 925
Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala
930 935 940
Thr Thr
945
<210> 105
<211> 2838
<212> DNA
<213> 黑猩猩腺病毒- ChAd 30六邻体
<400> 105
atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120
ctggggaaca agtttaggaa ccccaccgtg gcacccaccc acgatgtgac caccgaccga 180
agccagcggc tgatgctgcg ctttgtgccc gttgatcgtg aggacaatac ttactcgtac 240
aaagttcgtt acacactggc tgtgggcgac aacagagtgc tagatatggc cagcaccttc 300
tttgacatca gaggggtgct tgacagaggt cccagcttca agccctactc tggcacagct 360
tacaactctc tggctcctaa gggagctcct aatcctagcc aatggctaga acaatcaacg 420
acagagggag aagacgatcc aactaacact acacacacat ttggaatagc ttctatgaaa 480
ggagaaaaca tcaccaaaga aggtttgcaa attggaaaag aagtaaccac tactggagat 540
aaaccaattt atgcagataa aacctttcag ccagaacccc aagtgggaga agagacttgg 600
actgatactg acgggacaaa tgaaaagttt ggcggtagaa ctcttaaaag tgctactaat 660
atgaaaccat gctatgggtc ttttgctagg cccacaaaca aacaaggcgg acaagctaaa 720
accagaaaag tagcggcagt tgatgggggg gaggaaactg aagaaccaga catcgacatg 780
gtgttttatg atgatagagg tgctacagaa gccatgatgg ctcctgaagt tgtactttat 840
gcagaaaatg taaatctgga aacaccagac acccatgtgg tgtacaaacc aggaacctct 900
gatattaatt ctcatgaaaa tttgggtcag caggctatgc caaacaggcc caattacatt 960
ggattcagag ataactttgt tggactcatg tactacaata gtactggcaa tatgggtgtg 1020
ttggcagggc aggcatcaca gctaaatgca gtagttgact tgcaagacag aaacactgag 1080
ctatcgtacc agctcttact tgattccctg ggcgacagaa ctcgatattt cagcatgtgg 1140
aaccaggctg tggatagcta tgaccctgat gtgcgcatta ttgaaaatca tggtatcgaa 1200
gatgaactac caaattactg cttccctctt gatggaatag gaccaggtaa aacataccaa 1260
ggtattaaag aaaaacaagg tgatgaggcc aacaaatggg aacaagacaa aacctatgcc 1320
acctctaatg aaatagccat aggtaataac ctggctatgg aaattaatat ccaggctaac 1380
ctttggagaa gttttctgta ctccaacgtg gctctgtacc ttccagacgc ttacaagtac 1440
acgccggcca acattacttt acctgccaat accaacacct atgaatacat gaacgggcga 1500
gtggtggcac catctttggt tgattcctac atcaacattg gtgccaggtg gtctcttgac 1560
ccaatggaca atgtgaaccc cttcaatcac caccgcaacg ctgggctgcg ttacagatcc 1620
atgcttctgg gcaatggtcg ctatgtgcct ttccacatcc aagtgcctca aaaattcttt 1680
gctatcaaaa acctgcttct cctccccgga tcctacacct atgagtggaa cttcagaaag 1740
gacgtaaaca tggtcctgca gagttccctt ggtaatgatc tcagaactga tggtgctagc 1800
attagtttta ccagcatcaa cctctatgcc acctttttcc caatggctca caacactgct 1860
tccacacttg aagccatgct gcgcaatgac accaatgacc agtcattcaa tgactacctt 1920
tctgcagcta acatgctcta cccaattcca gcaaatgcta ccaacattcc catttccatt 1980
ccctctcgca actgggctgc cttcaggggc tggtcattca ccagactcaa aaccaaggag 2040
actccctctt tgggatcagg ctttgatccc tactttgttt actctggctc cattccctac 2100
ctggatggta ccttctacct caaccacact ttcaaaaagg tttccattat gtttgattcc 2160
tcagtcagct ggccgggcaa tgacagattg ctaactccaa atgagttcga aatcaagcgc 2220
actgtggatg gggaagggta caatgtagct caatgcaaca tgaccaagga ctggttcctg 2280
gttcagatgc ttgccaacta taacattggc taccagggct tctacatccc agaggggtac 2340
aaggatcgca tgtattcctt cttcagaaac ttccagccca tgagcagaca ggtggttgat 2400
gaagttaatt acaaggagta ccaagccgtc acacttgctt accaacacaa caactctggc 2460
tttgtgggtt accttgcacc cactatgagg cagggagaac cttaccccgc taactaccca 2520
taccccctaa tcggaaccac tgctgttaag agtgttaccc acaaaaagtt cctgtgcgac 2580
aggaccatgt ggcgcatccc cttctccagc aacttcatgt ccatgggtgc ccttaccgac 2640
ctgggacaga acatgcttta tgccaactca tcccatgcgc tggacatgac ttttgaggtg 2700
gatcccatgg atgagcccac cctgctttat cttcttttcg aagttttcga cgtggtcaga 2760
gcgcaccagc cacaccgcgg cgtcatcgag gctgtctacc tgcgtactcc attctcagct 2820
ggtaacgcca ccacataa 2838
<210> 106
<211> 945
<212> PRT
<213> 黑猩猩腺病毒- ChAd 30六邻体
<400> 106
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Pro Ser Gln Trp Leu Glu Gln Ser Thr Thr Glu Gly Glu
130 135 140
Asp Asp Pro Thr Asn Thr Thr His Thr Phe Gly Ile Ala Ser Met Lys
145 150 155 160
Gly Glu Asn Ile Thr Lys Glu Gly Leu Gln Ile Gly Lys Glu Val Thr
165 170 175
Thr Thr Gly Asp Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu
180 185 190
Pro Gln Val Gly Glu Glu Thr Trp Thr Asp Thr Asp Gly Thr Asn Glu
195 200 205
Lys Phe Gly Gly Arg Thr Leu Lys Ser Ala Thr Asn Met Lys Pro Cys
210 215 220
Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys Gln Gly Gly Gln Ala Lys
225 230 235 240
Thr Arg Lys Val Ala Ala Val Asp Gly Gly Glu Glu Thr Glu Glu Pro
245 250 255
Asp Ile Asp Met Val Phe Tyr Asp Asp Arg Gly Ala Thr Glu Ala Met
260 265 270
Met Ala Pro Glu Val Val Leu Tyr Ala Glu Asn Val Asn Leu Glu Thr
275 280 285
Pro Asp Thr His Val Val Tyr Lys Pro Gly Thr Ser Asp Ile Asn Ser
290 295 300
His Glu Asn Leu Gly Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile
305 310 315 320
Gly Phe Arg Asp Asn Phe Val Gly Leu Met Tyr Tyr Asn Ser Thr Gly
325 330 335
Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val
340 345 350
Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp
355 360 365
Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val
370 375 380
Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Ile Glu
385 390 395 400
Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Gly Ile Gly Pro Gly
405 410 415
Lys Thr Tyr Gln Gly Ile Lys Glu Lys Gln Gly Asp Glu Ala Asn Lys
420 425 430
Trp Glu Gln Asp Lys Thr Tyr Ala Thr Ser Asn Glu Ile Ala Ile Gly
435 440 445
Asn Asn Leu Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser
450 455 460
Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ala Tyr Lys Tyr
465 470 475 480
Thr Pro Ala Asn Ile Thr Leu Pro Ala Asn Thr Asn Thr Tyr Glu Tyr
485 490 495
Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ser Tyr Ile Asn
500 505 510
Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe
515 520 525
Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly
530 535 540
Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe
545 550 555 560
Ala Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp
565 570 575
Asn Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn
580 585 590
Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu
595 600 605
Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu
610 615 620
Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu
625 630 635 640
Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Ile
645 650 655
Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser
660 665 670
Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe
675 680 685
Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr
690 695 700
Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser
705 710 715 720
Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe
725 730 735
Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys
740 745 750
Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn
755 760 765
Ile Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Gly Tyr Lys Asp Arg Met
770 775 780
Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp
785 790 795 800
Glu Val Asn Tyr Lys Glu Tyr Gln Ala Val Thr Leu Ala Tyr Gln His
805 810 815
Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly
820 825 830
Glu Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala
835 840 845
Val Lys Ser Val Thr His Lys Lys Phe Leu Cys Asp Arg Thr Met Trp
850 855 860
Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp
865 870 875 880
Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ser His Ala Leu Asp Met
885 890 895
Thr Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu
900 905 910
Phe Glu Val Phe Asp Val Val Arg Ala His Gln Pro His Arg Gly Val
915 920 925
Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr
930 935 940
Thr
945
<210> 107
<211> 2877
<212> DNA
<213> 黑猩猩腺病毒- ChAd 31六邻体
<400> 107
atggcgaccc catcgatgat gccgcagtgg tcgtacatgc acatctcggg ccaggacgcc 60
tcggagtacc tgagccccgg gctggtgcag ttcgcccgcg ccaccgagag ctacttcagc 120
ctgagtaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgg 180
tctcagcgcc tgacgctgcg gttcattccc gtggaccgcg aggacaccgc gtactcgtac 240
aaggcgcggt tcaccctggc cgtgggcgac aaccgcgtgc tggacatggc ctccacctac 300
tttgacatcc gcggggtgct ggaccggggc cccactttca agccttactc tggcaccgcc 360
tacaactccc tggcccccaa gggcgctccc aactcctgcg agtgggagca attagaagaa 420
gcccaggccg ctgtggaaga cgaagaatta gaagatgaag acgaggaacc acaggatgag 480
gcacctgtga aaaaaaccca tgtatacgct caggctcccc tttctggaga agaaattact 540
aaaaacggtt tgcaaatagg gtcagataac acagaagccc agtctaagcc catatatgca 600
gatcctacat tccagcctga accccaaatc ggggaatccc agtggaatga ggcagatgct 660
acagttgccg gcggtagagt gctaaagaaa tccactccca tgaagccatg ctatggttcc 720
tatgcaagac ccacaaactc caatggaggt caaggtgtgc tggtggctga tgataagggg 780
gttcttcaat ctaaagttga attgcaattt ttttcaaata ctactactct taatcagcgg 840
gagggtaacg atacaaaacc aaaagtggtg ctgtatagcg aagatgtgca catggaaact 900
ccagacaccc acatttctta caagcccaca aaaagcgatg acaattcaaa aatcatgctg 960
ggtcagcagt ccatgcccaa cagacctaat tacatcggct tcagagacaa ctttatcggc 1020
ctcatgtatt acaatagcac tggcaacatg ggagtgcttg caggtcaggc ctctcagttg 1080
aatgcagtgg tggacttgca agacagaaac acagaactgt cctaccagct cttgcttgat 1140
tccatgggtg acagaaccag atacttttcc atgtggaatc aggcagtgga cagttatgac 1200
ccagatgtca gaattattga aaatcatgga actgaagacg agctccccaa ctattgtttc 1260
cctctgggcg gcataggggt aactgacact taccaggcca ttaaaaccaa tggcaatggt 1320
caagaaaacc caacctggga aaaagataca gagtttgcag accgcaatga aataggggtg 1380
ggaaacaatt ttgctatgga gatcaacctc agtgccaacc tgtggagaaa cttcctgtac 1440
tccaacgtgg cgctgtacct accagacaag cttaagtaca acccctccaa tgtggacatc 1500
tctgacaacc ccaacaccta cgattacatg aacaagcgag tggtggcccc ggggctggtg 1560
gactgctaca tcaacctggg cgcgcgctgg tcgctggact acatggacaa cgtcaacccc 1620
ttcaaccacc accgcaatgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680
tatgtgccct tccacatcca ggtgccccag aagttctttg ccatcaagaa cctcctcctc 1740
ctgccgggct cctacaccta cgagtggaac ttcaggaagg atgtcaacat ggtcctccag 1800
agctctctgg gtaacgatct cagggtggac ggggccagca tcaagttcga gagcatctgc 1860
ctctacgcca ccttcttccc catggcccac aacacggcct ccacgctcga ggccatgctc 1920
aggaacgaca ccaacgacca gtccttcaat gactaccttt ccgccgccaa catgctctac 1980
cccatacccg ccaacgccac caacgtcccc atctccatcc cctcgcgcaa ctgggcggcc 2040
ttccgcggct gggccttcac ccgcctcaag accaaggaga ccccctccct gggctcggga 2100
ttcgacccct actacaccta ctcgggctct attccctacc tggacggcac cttctacctc 2160
aaccacactt tcaagaaggt ctcggtcacc ttcgactcct cggtcagctg gccgggcaac 2220
gaccgtctgc tcacccccaa cgagttcgag atcaagcgct cggtcgacgg ggagggctac 2280
aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggccaactac 2340
aacatcggct accagggctt ctacatccca gagagctaca aggacaggat gtactccttc 2400
ttcaggaact tccagcccat gagccggcag gtggtggacc agaccaagta caaggactac 2460
caggaggtgg gcatcatcca ccagcacaac aactcgggct tcgtgggcta cctcgccccc 2520
accatgcgcg agggacaggc ctaccccgcc aacttcccct acccgctcat aggcaagacc 2580
gcggtcgaca gcatcaccca gaaaaagttc ctctgcgacc gcaccctctg gcgcatcccc 2640
ttctccagca acttcatgtc catgggtgcg ctctcggacc tgggccagaa cttgctctac 2700
gccaactccg cccacgccct cgacatgacc ttcgaggtcg accccatgga cgagcccacc 2760
cttctctatg ttctgttcga agtctttgac gtggtccggg tccaccagcc gcaccgcggc 2820
gtcatcgaga ccgtgtacct gcgtacgccc ttctcggccg gcaacgccac cacctaa 2877
<210> 108
<211> 958
<212> PRT
<213> 黑猩猩腺病毒- ChAd 31六邻体
<400> 108
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala
130 135 140
Val Glu Asp Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu
145 150 155 160
Ala Pro Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly
165 170 175
Glu Glu Ile Thr Lys Asn Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu
180 185 190
Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro
195 200 205
Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly
210 215 220
Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Ser Asn Gly Gly Gln Gly Val Leu Val Ala
245 250 255
Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu Leu Gln Phe Phe Ser
260 265 270
Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly Asn Asp Thr Lys Pro Lys
275 280 285
Val Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr His
290 295 300
Ile Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Ile Met Leu
305 310 315 320
Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp
325 330 335
Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val
340 345 350
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp
355 360 365
Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp
370 375 380
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp
385 390 395 400
Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro
405 410 415
Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln
420 425 430
Ala Ile Lys Thr Asn Gly Asn Gly Gln Glu Asn Pro Thr Trp Glu Lys
435 440 445
Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe
450 455 460
Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe Leu Tyr
465 470 475 480
Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser
485 490 495
Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys
500 505 510
Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala
515 520 525
Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His
530 535 540
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg
545 550 555 560
Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys
565 570 575
Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg
580 585 590
Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg
595 600 605
Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr
610 615 620
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu
625 630 635 640
Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala
645 650 655
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
660 665 670
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg
675 680 685
Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr
690 695 700
Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu
705 710 715 720
Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser
725 730 735
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
740 745 750
Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr
755 760 765
Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr
770 775 780
Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe
785 790 795 800
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys
805 810 815
Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser
820 825 830
Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr
835 840 845
Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser
850 855 860
Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro
865 870 875 880
Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln
885 890 895
Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu
900 905 910
Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val
915 920 925
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr
930 935 940
Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955
<210> 109
<211> 2856
<212> DNA
<213> 黑猩猩腺病毒- ChAd 37六邻体
<400> 109
atggccaccc catcgatgct gccccagtgg gcatacatgc acatcgccgg acaggatgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgtg ccacagacac ctacttcaat 120
ctggggaaca agtttaggaa ccccaccgtg gcccctaccc acgatgtgac caccgaccgt 180
agccagcggc tgatgctgcg ctttgtgccc gttgatcggg aggacaatac ctactcttac 240
aaagttcgct acacactggc tgtgggcgac aacagagtgc tggacatggc cagcaccttc 300
tttgacatca ggggggtgct tgacagaggt cccagtttca agccatactc tggcacagct 360
tacaattccc tggcgcctaa gggcgcgccc aatacatgcc agtggattgc caagggggcg 420
cctgttaccg atcaagacaa tgaagaacag gaattaacag atgttactta cgcttttggc 480
aatgctccag tacaagcaga agccaaaatt acaaaagatg gtctgccagt aggtttggaa 540
attacagaag atgaacaaaa gtcaatttat gcagacaaat tgtatcagcc agagccccaa 600
attggcgatg aacaatggca tgacaccact ggcactaatg aacaatacgg cggcagagct 660
ctaaaaccgg ccaccaacat gaaaccatgt tatggctcat ttgccagacc cacaaataaa 720
aaaggcggtc aggctaaaac tagaaaaata gaaaaggaag agaatggagt taaaaccgta 780
actgaagaag ctgacattga tatggacttt tatgacttaa gatcacaaag agcaaatttt 840
gatcctaaaa ttgttcttta ttctgaaaat gtaaatttgg aaactccaga tacacatatt 900
gtgtataaac caggaacaga tgaaactagt tcctctgtta acttgggaca gcaggcaatg 960
cccaacagac ccaactacat tggttttagg gacaacttca ttggacttat gttttacaac 1020
agtaccggca acatgggcgt gctggccggg caagcttctc agttaaatgc tgtggttgac 1080
ttgcaggaca ggaacacaga actgtcctac cagctgctgc ttgactctct gggtgacaga 1140
accagatact ttagcatgtg gaatcaggcc gtggatagct atgacccaga cgtgcgcatt 1200
attgaaaacc acggtgtgga agacgaactt cctaactatt gttttccatt agatggagtg 1260
ggaccaatta cgggcactta tcagggggtt gagcctgatg gaaacaatgg aaactggaag 1320
aaaaacacaa acataaatgg agcaaatgaa attggcaagg gaaataacta tgctatggaa 1380
attaatctac aagctaacct ctggagaagt tttctatatt ccaatgtggc tctgtattta 1440
ccagacggtt acaaatatac cccagccaat gttacactgc cagaaaacaa aaacacctat 1500
ggctatataa acggacgagt agtatcccca tctttggtgg attcatacat caacattgga 1560
gccagatggt ctttggatct tatggacaat gtaaacccat tcaatcacca ccgcaatgca 1620
ggcctgcgtt accgttccat gcttttagga aatggtcgct atgtgccttt ccacatccaa 1680
gtgcctcaga aaatctttgc tgtcaagaac ctgttgcttc ttcccggctc ctacacctat 1740
gagtggaact tcagaaagga cgtaaacatg gtcctgcaaa gttcccttgg taatgatctc 1800
agaactgatg gtgctagcat cagttttacc agcatcaatc tatatgctac ctttttcccc 1860
atggcccaca acactgcttc cacccttgaa gccatgctgc gcaatgacac caatgaccag 1920
tcatttaatg actacctttc tgcagctaac atgctctacc ctattccagc caatgcaacc 1980
aacatcccca tttccattcc ctctcgcaat tgggccgcct tcaggggctg gtccttcacc 2040
agactcaaaa ccaaggagac cccatctctg ggatcagggt tcgatcccta ctttgtctat 2100
tctggttcta ttccctacct tgatggcacc ttctacctta accacacttt caagaaggtc 2160
tccatcatgt ttgactcctc agtcagctgg ccaggcaatg acaggcttct aactccaaat 2220
gagtttgaaa tcaaacgcac tgtggatggg gaagggtaca atgtggctca atgcaacatg 2280
accaaggact ggttcctggt tcaaatgctc gccaactaca acattggcta ccagggcttc 2340
tacatcccag aggggtacaa ggatcgcatg tactccttct tcagaaactt ccagcccatg 2400
agtaggcagg tggttgatga gatcaactac aaggagtacc aagctgtcac acttgcttac 2460
cagcacaaca actctggctt tgtgggttac catgcaccca ctctccgtca gggtcaacca 2520
tacccagcta actacccata cccgcttatt ggaaccactg ctgtcaccag cgtcacccag 2580
aaaaagttct tgtgcgacag gaccatgtgg cgcatcccct tctccagcaa cttcatgtcc 2640
atgggtgccc ttaccgacct ggggcagaac atgctttatg ctaactcagc tcatgcgctg 2700
gacatgactt ttgaggtgga tcccatggat gagcccacac tgctttatct tcttttcgaa 2760
gtcttcgacg tggtcagagt gcaccagcca caccgcggcg tcatcgaggc cgtctacctg 2820
cgcacaccgt tctcggccgg caacgccacc acataa 2856
<210> 110
<211> 951
<212> PRT
<213> 黑猩猩腺病毒- ChAd 37六邻体
<400> 110
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Ile Ala Lys Gly Ala Pro Val Thr Asp
130 135 140
Gln Asp Asn Glu Glu Gln Glu Leu Thr Asp Val Thr Tyr Ala Phe Gly
145 150 155 160
Asn Ala Pro Val Gln Ala Glu Ala Lys Ile Thr Lys Asp Gly Leu Pro
165 170 175
Val Gly Leu Glu Ile Thr Glu Asp Glu Gln Lys Ser Ile Tyr Ala Asp
180 185 190
Lys Leu Tyr Gln Pro Glu Pro Gln Ile Gly Asp Glu Gln Trp His Asp
195 200 205
Thr Thr Gly Thr Asn Glu Gln Tyr Gly Gly Arg Ala Leu Lys Pro Ala
210 215 220
Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg Pro Thr Asn Lys
225 230 235 240
Lys Gly Gly Gln Ala Lys Thr Arg Lys Ile Glu Lys Glu Glu Asn Gly
245 250 255
Val Lys Thr Val Thr Glu Glu Ala Asp Ile Asp Met Asp Phe Tyr Asp
260 265 270
Leu Arg Ser Gln Arg Ala Asn Phe Asp Pro Lys Ile Val Leu Tyr Ser
275 280 285
Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Pro
290 295 300
Gly Thr Asp Glu Thr Ser Ser Ser Val Asn Leu Gly Gln Gln Ala Met
305 310 315 320
Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu
325 330 335
Met Phe Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala
340 345 350
Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu
355 360 365
Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe
370 375 380
Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile
385 390 395 400
Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro
405 410 415
Leu Asp Gly Val Gly Pro Ile Thr Gly Thr Tyr Gln Gly Val Glu Pro
420 425 430
Asp Gly Asn Asn Gly Asn Trp Lys Lys Asn Thr Asn Ile Asn Gly Ala
435 440 445
Asn Glu Ile Gly Lys Gly Asn Asn Tyr Ala Met Glu Ile Asn Leu Gln
450 455 460
Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu
465 470 475 480
Pro Asp Gly Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu Pro Glu Asn
485 490 495
Lys Asn Thr Tyr Gly Tyr Ile Asn Gly Arg Val Val Ser Pro Ser Leu
500 505 510
Val Asp Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Leu Met
515 520 525
Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr
530 535 540
Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln
545 550 555 560
Val Pro Gln Lys Ile Phe Ala Val Lys Asn Leu Leu Leu Leu Pro Gly
565 570 575
Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Val Leu
580 585 590
Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser
595 600 605
Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn
610 615 620
Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln
625 630 635 640
Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro
645 650 655
Ala Asn Ala Thr Asn Ile Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala
660 665 670
Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro
675 680 685
Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile
690 695 700
Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val
705 710 715 720
Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu
725 730 735
Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly
740 745 750
Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln
755 760 765
Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Ile Pro Glu
770 775 780
Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met
785 790 795 800
Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys Glu Tyr Gln Ala Val
805 810 815
Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr His Ala
820 825 830
Pro Thr Leu Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro
835 840 845
Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu
850 855 860
Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser
865 870 875 880
Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser
885 890 895
Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met Asp Glu Pro
900 905 910
Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp Val Val Arg Val His
915 920 925
Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe
930 935 940
Ser Ala Gly Asn Ala Thr Thr
945 950
<210> 111
<211> 2817
<212> DNA
<213> 黑猩猩腺病毒- ChAd 38六邻体
<400> 111
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacgccc tggcccctaa agccgctcct aatcctagcc agtgggagga aaccactact 420
ggaacggatg gaaatgctgc tactacaact acacatagtt ttggcctggc tgctatgaaa 480
ggggacaata ttacatctga cggtttgcaa ataggaacag atgctacttc tggagaggaa 540
aaacccatct atgcagataa actgtaccag ccagaacccc aaatagggga agagtcatgg 600
actgatactg atggaaccaa tgaaaaattc ggaggaagag tccttaaaaa ggacacaagc 660
atgaaaccct gctacgggtc atttgccaaa ccaaccaata acaaaggtgg tcaagcaaaa 720
caaaaggcaa ctgaaggaac cgctgtagaa tatgatgtag acatgaactt ttttgatggt 780
agagatgcag ctgctaactt tactccagaa gtagtgttgt atgctgaaaa tgtggatttg 840
gaaactccag atacacatat tgtatacaaa ccaggaacct cagatgtgag ttcccatgtt 900
aatttgggac agcaagccat gcccaacaga cccaactaca ttggtttcag agacaacttt 960
attggtctca tgtattacaa cagcactggc aatatggggg tgctggccgg tcaggcttct 1020
cagctgaatg ctgtggttga cttgcaagac agaaacactg aactgtccta ccagctgttg 1080
cttgactctt tgggtgacag aactcggtat ttcagtatgt ggaatcaggc ggtggacagc 1140
tatgatcctg atgtgcgcat cattgaaaat catggtatag aagatgagct tcccaactat 1200
tgctttccta ttgacgctgt gggtattact agaacttatc aaggtatcaa aacgcaaaat 1260
ggtcaaacta caacttggga aaaggacacc agtgttagta cggccaatga aataggcatt 1320
ggcaacaatc ttgccatgga aatcaacatc caagccaacc tgtggaggaa cttcctctac 1380
gccaacgtgg ccctgtacct gcccgattct tacaagtaca caccggccaa cgtcaccctg 1440
cccaccaata ccaacaccta cgattacatg aacggccggg tggtggcgcc ctcgctggtg 1500
gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggataa cgtgaatccc 1560
ttcaaccacc accgcaacgc ggggctgcgc taccgctcca tgctcctggg caacgggcgc 1620
tacgtgccct tccacatcca ggtgccccag aaatttttcg ccatcaagag cctcctgctc 1680
ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat gatcctgcag 1740
agctccctcg gcaacgacct gcgcacggac ggggcctcca tctccttcac cagcatcaac 1800
ctctacgcca ccttcttccc catggcgcac aacacggcct ccacgctcga ggccatgctg 1860
cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa catgctctac 1920
cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa ctgggccgcc 1980
ttccgcggct ggtccttcac gcgcctcaag accaaggaga cgccctcgct gggctccggg 2040
ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac cttctacctc 2100
aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg gcccggcaac 2160
gaccggctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg cgagggctac 2220
aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggcccactac 2280
aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat gtactccttc 2340
ttccgcaact tccaacccat gagccgccag gtggtggacg aggtcaacta caaggactac 2400
caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta cctcgcgccc 2460
accatgcgcc agggccagcc ctaccccgcc aactacccct acccgctcat cggcaagagc 2520
gccgtcacca gcgtcaccca gaaaaagttc ctctgcgaca gggtcatgtg gcgcatcccc 2580
ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa catgctctat 2640
gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga tgagtccacc 2700
cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc ccaccgcggc 2760
gtcatcgagg ccgtctacct gcgcaccccc ttctcggccg gtaacgccac cacctaa 2817
<210> 112
<211> 938
<212> PRT
<213> 黑猩猩腺病毒- ChAd 38六邻体
<400> 112
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ala Leu Ala Pro Lys Ala
115 120 125
Ala Pro Asn Pro Ser Gln Trp Glu Glu Thr Thr Thr Gly Thr Asp Gly
130 135 140
Asn Ala Ala Thr Thr Thr Thr His Ser Phe Gly Leu Ala Ala Met Lys
145 150 155 160
Gly Asp Asn Ile Thr Ser Asp Gly Leu Gln Ile Gly Thr Asp Ala Thr
165 170 175
Ser Gly Glu Glu Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln Pro Glu
180 185 190
Pro Gln Ile Gly Glu Glu Ser Trp Thr Asp Thr Asp Gly Thr Asn Glu
195 200 205
Lys Phe Gly Gly Arg Val Leu Lys Lys Asp Thr Ser Met Lys Pro Cys
210 215 220
Tyr Gly Ser Phe Ala Lys Pro Thr Asn Asn Lys Gly Gly Gln Ala Lys
225 230 235 240
Gln Lys Ala Thr Glu Gly Thr Ala Val Glu Tyr Asp Val Asp Met Asn
245 250 255
Phe Phe Asp Gly Arg Asp Ala Ala Ala Asn Phe Thr Pro Glu Val Val
260 265 270
Leu Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr His Ile Val
275 280 285
Tyr Lys Pro Gly Thr Ser Asp Val Ser Ser His Val Asn Leu Gly Gln
290 295 300
Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
305 310 315 320
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
325 330 335
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
340 345 350
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr
355 360 365
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
370 375 380
Val Arg Ile Ile Glu Asn His Gly Ile Glu Asp Glu Leu Pro Asn Tyr
385 390 395 400
Cys Phe Pro Ile Asp Ala Val Gly Ile Thr Arg Thr Tyr Gln Gly Ile
405 410 415
Lys Thr Gln Asn Gly Gln Thr Thr Thr Trp Glu Lys Asp Thr Ser Val
420 425 430
Ser Thr Ala Asn Glu Ile Gly Ile Gly Asn Asn Leu Ala Met Glu Ile
435 440 445
Asn Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala
450 455 460
Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu
465 470 475 480
Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala
485 490 495
Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu
500 505 510
Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly
515 520 525
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe
530 535 540
His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu
545 550 555 560
Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn
565 570 575
Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala
580 585 590
Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met
595 600 605
Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr
610 615 620
Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr
625 630 635 640
Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg
645 650 655
Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys
660 665 670
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser
675 680 685
Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
690 695 700
Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn
705 710 715 720
Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp
725 730 735
Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
740 745 750
Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr
755 760 765
Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe
770 775 780
Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr
785 790 795 800
Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly
805 810 815
Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr
820 825 830
Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys
835 840 845
Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn
850 855 860
Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr
865 870 875 880
Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met
885 890 895
Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val
900 905 910
Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg
915 920 925
Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935
<210> 113
<211> 2781
<212> DNA
<213> 黑猩猩腺病毒- ChAd 44六邻体
<400> 113
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacctac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggcccccaa gggagcgccc aatcccagcc agtgggaaca aactgaaacc 420
aatgttaata aaacacacac cttcggaatg gcagccatga aaggagaggc tattgacaaa 480
aatggtctgc aaattggaac tgacgctgcg gatcaggata aaccaattta tgcagataaa 540
acattccagc ctgaacctca agtaggagag gaagactgga ttgacaaagc agatttttat 600
ggcggaagag ctcttaaaaa agataccaag atgaaaccat gctatggctc atttgccaaa 660
cctacaaatg tcaagggagg acaggcaacg cccaggacta aagcagatgg aactactgag 720
cctgatattg acatgaactt ctttgaccca accactatta acacaccaga tgtagtgttg 780
tatgctgaaa atgttgattt gcaaactcca gacacccata tagtttacaa agcaggaact 840
tcagatgaca gttctgaggt caatttggct cagcaagcta tgcctaacag gcccaactac 900
attggtttca gagacaactt tatcggactt atgtattaca atagcactgg caatatgggt 960
gtgctcgctg gtcaggcttc ccagctaaat gctgtggtgg acttgcaaga cagaaacacc 1020
gagctgtcct accagctctt gcttgactct ctgggtgaca gaaccaggta tttcagtatg 1080
tggaatcagg cggtggacag ctatgatcct gatgtgcgca ttattgaaaa ccatggtgtg 1140
gaggatgaac tgccaaacta ttgctttcct ttggatggtg tgggcactaa taccgcatac 1200
caaggcgtta aagttaagac aactaatgga aacgacacgt gggaaaaaga tgaaactgtt 1260
tatgagttta atcaaattgg aaagggggat atctatgcta tggaaatcaa cattcaagcc 1320
aacctgtgga gaagttttct ctactcgaac gtggccctgt acctgcccga ttcttacaag 1380
tacacgccgg ccaacgtcac cctgcccacc aacaccaaca cctacgatta catgaacggg 1440
agagtggtgc ctccctcgct ggtggacgcc tacatcaaca tcggggcgcg ctggtcgctg 1500
gaccccatgg acaacgtgaa ccccttcaac caccaccgca acgcggggct gcgctaccgc 1560
tccatgctcc tgggcaacgg gcgcttcgtg cccttccaca tccaggtgcc ccagaaattt 1620
ttcgccatca agagcctcct gctcctgcca gggtcctaca cctacgagtg gaacttccgc 1680
aaggacgtca acatgatcct gcagagctcc ctcggcaacg acctgcgcac ggacggggcc 1740
tccatctcct tcaccagtat caacctctac gccaccttct tccccatggc gcacaacacg 1800
gcctccacgc tcgaggccat gctgcgcaac gacaccaacg accagtcctt caacgactac 1860
ctctcggcgg ccaacatgct ctaccccatc ccggccaacg ccaccaacgt gcccatctcc 1920
atcccctcgc gcaactgggc cgccttccgc ggctggtcct tcacgcgcct caagaccaag 1980
gagacgccct cgctgggctc cgggttcgac ccctacttcg tctactcggg ctccatcccc 2040
tacctcgacg gcaccttcta cctcaaccac accttcaaga aggtctccat caccttcgac 2100
tcctccgtca gctggcccgg caacgaccgc ctcctgacgc ccaacgagtt cgaaatcaag 2160
cgcaccgtcg acggagaggg gtacaacgtg gcccagtgca acatgaccaa ggactggttc 2220
ctggtccaga tgctggccca ctacaacatc ggctaccagg gcttctacgt gcccgagggc 2280
tacaaggacc gcatgtactc cttcttccgc aacttccagc ccatgagccg ccaggtggtg 2340
gacgaggtca actacaagga ctaccaggcc gtcaccctgg cctaccagca caacaactcg 2400
ggcttcgtcg gctacctcgc gcccaccatg cgccagggcc agccctaccc cgccaactac 2460
ccgtacccgc tcatcggcaa gagcgccgtc accagcgtca cccagaaaaa gttcctctgc 2520
gacagggtca tgtggcgcat ccccttctcc agcaacttca tgtccatggg cgcgctcacc 2580
gacctcggcc agaacatgct ctatgccaac tccgcccacg cgctagacat gaatttcgaa 2640
gtcgacccca tggatgagtc cacccttctc tatgttgtct tcgaagtctt cgacgtcgtc 2700
cgagtgcacc agccccaccg cggcgtcatc gaggccgtct acctgcgcac ccccttctcg 2760
gccggtaacg ccaccaccta a 2781
<210> 114
<211> 926
<212> PRT
<213> 黑猩猩腺病毒- ChAd 44六邻体
<400> 114
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Pro Ser Gln Trp Glu Gln Thr Glu Thr Asn Val Asn Lys
130 135 140
Thr His Thr Phe Gly Met Ala Ala Met Lys Gly Glu Ala Ile Asp Lys
145 150 155 160
Asn Gly Leu Gln Ile Gly Thr Asp Ala Ala Asp Gln Asp Lys Pro Ile
165 170 175
Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val Gly Glu Glu Asp
180 185 190
Trp Ile Asp Lys Ala Asp Phe Tyr Gly Gly Arg Ala Leu Lys Lys Asp
195 200 205
Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val
210 215 220
Lys Gly Gly Gln Ala Thr Pro Arg Thr Lys Ala Asp Gly Thr Thr Glu
225 230 235 240
Pro Asp Ile Asp Met Asn Phe Phe Asp Pro Thr Thr Ile Asn Thr Pro
245 250 255
Asp Val Val Leu Tyr Ala Glu Asn Val Asp Leu Gln Thr Pro Asp Thr
260 265 270
His Ile Val Tyr Lys Ala Gly Thr Ser Asp Asp Ser Ser Glu Val Asn
275 280 285
Leu Ala Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
290 295 300
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
305 310 315 320
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
325 330 335
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly
340 345 350
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
355 360 365
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu
370 375 380
Pro Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Thr Asn Thr Ala Tyr
385 390 395 400
Gln Gly Val Lys Val Lys Thr Thr Asn Gly Asn Asp Thr Trp Glu Lys
405 410 415
Asp Glu Thr Val Tyr Glu Phe Asn Gln Ile Gly Lys Gly Asp Ile Tyr
420 425 430
Ala Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr
435 440 445
Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala
450 455 460
Asn Val Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly
465 470 475 480
Arg Val Val Pro Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala
485 490 495
Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His
500 505 510
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg
515 520 525
Phe Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys
530 535 540
Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg
545 550 555 560
Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg
565 570 575
Thr Asp Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr
580 585 590
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu
595 600 605
Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala
610 615 620
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
625 630 635 640
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg
645 650 655
Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr
660 665 670
Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu
675 680 685
Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser
690 695 700
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
705 710 715 720
Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr
725 730 735
Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr
740 745 750
Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe
755 760 765
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn
770 775 780
Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser
785 790 795 800
Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr
805 810 815
Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Thr Ser
820 825 830
Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro
835 840 845
Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln
850 855 860
Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu
865 870 875 880
Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val
885 890 895
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala
900 905 910
Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
915 920 925
<210> 115
<211> 2877
<212> DNA
<213> 黑猩猩腺病毒- ChAd 63六邻体
<400> 115
atgtatgtcc gccgaccaga aggaggaaga ggcgcgtcgc cgagttgcaa gatggccacc 60
ccatcgatgc tgccccagtg ggcgtacatg cacatcgccg gacaggacgc ttcggagtac 120
ctgagtccgg gtctggtgca gttcgcccgc gccacagaca cctacttcag tctggggaac 180
aagtttagga accccacggt ggcgcccacg cacgatgtga ccaccgaccg cagccagcgg 240
ctgacgctgc gcttcgtgcc cgtggaccgc gaggacaaca cctactcgta caaagtgcgc 300
tacacgctgg ccgtgggcga caaccgcgtg ctggacatgg ccagcaccta ctttgacatc 360
cgcggcgtgc tggatcgggg ccccagcttc aaaccctact ccggcaccgc ctacaacagc 420
ctagctccca agggagcgcc caacacctca cagtggaagg attccgacag caaaatgcat 480
acttttggag ttgctgccat gcccggtgtt gttggtaaaa aaatagaagc cgatggtctg 540
cctattggaa tagattcatc ctctggaact gacaccataa tttatgctga taaaactttc 600
caaccagagc cacaggttgg aagtgacagt tgggtcgaca ccaatggtgc agaggaaaaa 660
tatggaggta gagctcttaa ggacactaca aacatgaagc cctgctacgg ttcttttgcc 720
aggcctacca acaaagaagg tggacaggct aacataaaag attctgaaac tgccagcact 780
actcctaact atgatataga tttggcattc tttgacagca aaaatattgc agctaactac 840
gatccagata ttgtaatgta cacagaaaat gttgagttgc aaactccaga tactcatatt 900
gtgtttaagc caggaacttc agatgaaagt tcagaagcca atttgggcca gcaggccatg 960
cccaacagac ccaactacat cgggttcaga gacaacttta tcgggctcat gtactacaac 1020
agcactggca atatgggtgt actggctggt caggcctccc agctaaatgc tgtggtggac 1080
ttgcaggaca gaaacaccga actgtcctac cagctcttgc ttgactctct gggtgacaga 1140
accaggtatt tcagtatgtg gaatcaggcg gtggacagct atgaccccga tgtgcgcatt 1200
attgaaaatc acggtgtgga ggatgaactc cccaattatt gcttcccttt gaatggtgta 1260
ggctttacag atacttacca gggtgttaaa gttaagacag atacagccgc tactggtacc 1320
aatggaacgc agtgggacaa agatgatacc acagtcagca ctgccaatga gatccactca 1380
ggcaatcctt tcgccatgga gatcaacatc caggccaacc tgtggcggaa cttcctctac 1440
gcgaacgtgg cgctgtacct gcccgactcc tacaagtaca cgccggccaa catcacgctg 1500
ccgaccaaca ccaacaccta cgattacatg aacggccgcg tggtggcgcc ctcgctggtg 1560
gacgcctaca tcaacatcgg ggcgcgctgg tcgctggacc ccatggacaa cgtcaacccc 1620
ttcaaccacc accgcaacgc gggcctgcgc taccgctcca tgctcctggg caacgggcgc 1680
tacgtgccct tccacatcca ggtgccccaa aagtttttcg ccatcaagag cctcctgctc 1740
ctgcccgggt cctacaccta cgagtggaac ttccgcaagg acgtcaacat gatcctgcag 1800
agctccctcg gcaacgacct gcgcacggac ggggcctcca tcgccttcac cagcatcaac 1860
ctctacgcca ccttcttccc catggcgcac aacaccgcct ccacgctcga ggccatgctg 1920
cgcaacgaca ccaacgacca gtccttcaac gactacctct cggcggccaa catgctctac 1980
cccatcccgg ccaacgccac caacgtgccc atctccatcc cctcgcgcaa ctgggccgcc 2040
ttccgcggat ggtccttcac gcgcctcaag acccgcgaga cgccctcgct cggctccggg 2100
ttcgacccct acttcgtcta ctcgggctcc atcccctacc tcgacggcac cttctacctc 2160
aaccacacct tcaagaaggt ctccatcacc ttcgactcct ccgtcagctg gcccggcaac 2220
gaccgcctcc tgacgcccaa cgagttcgaa atcaagcgca ccgtcgacgg agagggatac 2280
aacgtggccc agtgcaacat gaccaaggac tggttcctgg tccagatgct ggcccactac 2340
aacatcggct accagggctt ctacgtgccc gagggctaca aggaccgcat gtactccttc 2400
ttccgcaact tccagcccat gagccgccag gtcgtggacg aggtcaacta caaggactac 2460
caggccgtca ccctggccta ccagcacaac aactcgggct tcgtcggcta cctcgcgccc 2520
accatgcgcc agggccagcc ctaccccgcc aactacccct acccgctcat cggcaagagc 2580
gccgtcgcca gcgtcaccca gaaaaagttc ctctgcgacc gggtcatgtg gcgcatcccc 2640
ttctccagca acttcatgtc catgggcgcg ctcaccgacc tcggccagaa catgctctac 2700
gccaactccg cccacgcgct agacatgaat ttcgaagtcg accccatgga tgagtccacc 2760
cttctctatg ttgtcttcga agtcttcgac gtcgtccgag tgcaccagcc ccaccgcggc 2820
gtcatcgagg ccgtctacct gcgcacgccc ttctcggccg gcaacgccac cacctaa 2877
<210> 116
<211> 941
<212> PRT
<213> 黑猩猩腺病毒- ChAd 63六邻体
<400> 116
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Ser Gln Trp Lys Asp Ser Asp Ser Lys Met His Thr
130 135 140
Phe Gly Val Ala Ala Met Pro Gly Val Val Gly Lys Lys Ile Glu Ala
145 150 155 160
Asp Gly Leu Pro Ile Gly Ile Asp Ser Ser Ser Gly Thr Asp Thr Ile
165 170 175
Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val Gly Ser Asp
180 185 190
Ser Trp Val Asp Thr Asn Gly Ala Glu Glu Lys Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Asp Thr Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg
210 215 220
Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Ile Lys Asp Ser Glu Thr
225 230 235 240
Ala Ser Thr Thr Pro Asn Tyr Asp Ile Asp Leu Ala Phe Phe Asp Ser
245 250 255
Lys Asn Ile Ala Ala Asn Tyr Asp Pro Asp Ile Val Met Tyr Thr Glu
260 265 270
Asn Val Glu Leu Gln Thr Pro Asp Thr His Ile Val Phe Lys Pro Gly
275 280 285
Thr Ser Asp Glu Ser Ser Glu Ala Asn Leu Gly Gln Gln Ala Met Pro
290 295 300
Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met
305 310 315 320
Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser
325 330 335
Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser
340 345 350
Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser
355 360 365
Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile
370 375 380
Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu
385 390 395 400
Asn Gly Val Gly Phe Thr Asp Thr Tyr Gln Gly Val Lys Val Lys Thr
405 410 415
Asp Thr Ala Ala Thr Gly Thr Asn Gly Thr Gln Trp Asp Lys Asp Asp
420 425 430
Thr Thr Val Ser Thr Ala Asn Glu Ile His Ser Gly Asn Pro Phe Ala
435 440 445
Met Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala
450 455 460
Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn
465 470 475 480
Ile Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg
485 490 495
Val Val Ala Pro Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg
500 505 510
Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg
515 520 525
Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr
530 535 540
Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser
545 550 555 560
Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys
565 570 575
Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr
580 585 590
Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe
595 600 605
Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg
610 615 620
Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn
625 630 635 640
Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile
645 650 655
Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu
660 665 670
Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe
675 680 685
Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn
690 695 700
His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp
705 710 715 720
Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg
725 730 735
Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys
740 745 750
Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln
755 760 765
Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe
770 775 780
Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr
785 790 795 800
Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly
805 810 815
Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro
820 825 830
Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val
835 840 845
Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe
850 855 860
Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn
865 870 875 880
Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val
885 890 895
Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe
900 905 910
Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val
915 920 925
Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935 940
<210> 117
<211> 2811
<212> DNA
<213> 黑猩猩腺病毒- ChAd 82六邻体
<400> 117
atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg acaggacgct 60
tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac ctacttcagt 120
ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac caccgaccgc 180
agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac ctactcgtac 240
aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc cagcacttac 300
tttgacatcc gcggcgtgct ggaccggggc cctagcttca aaccctactc cggcaccgcc 360
tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca aaatgaaaac 420
aatggtcaag gtcaagctaa gacacacacc tatggtgttg ctgctatggg cggacttgat 480
attacaaaag agggtcttaa aattgtaact gatgctagta aggaagatga caatgaaatt 540
tatgcagata aaacatatca gcccgagcct caaataggag aggaaaattg gcaagacact 600
aaaaactttt atggaggcag agctcttaaa aaagatacca agatgaagcc atgctatggc 660
tcatttgcca gacctaccaa tgtgaaggga gggcaagcca aagtgaaaac agaagaaaat 720
gttcagtcat ttgacataga tctggctttc tttgatattc caagcaccgg cacagggggc 780
aatggtacaa atgtaaatga taagccagac atggttatgt acactgaaaa tgtgaatctg 840
gagacgccag atactcatat tgtgtacaaa cctggaactt cagatgacag ctctgaagcc 900
aacttgtgcc agcaggccat gccaaacaga cccaactaca ttggtttcag agacaacttt 960
attgggctca tgtattacaa cagtactggc aatatggggg tgctggctgg tcaggcctcc 1020
cagctgaatg ctgtggttga cttgcaagac agaaacaccg agctgtcata ccagctcttg 1080
cttgactctc tgggtgacag aacccggtat ttcagcatgt ggaaccaggc ggtggacagt 1140
tatgaccctg atgtgcgcat tattgaaaac catggtgtgg aggatgaatt gccaaactat 1200
tgcttcccct tggatggagc tggcactaat gctgtatacc ggggtgttaa agcaaaagat 1260
aacggaaact gggaacaaga cacaggcgtt tcaagtatta accagatatg caaggggaac 1320
atctatgcca tggaaatcaa cattcaagcc aacctgtgga gaagtttcct ttactcgaac 1380
gtggccctgt acctgcccga ctcttacaag tacacgccgg ccaacatcac cctgcccacc 1440
aacaccaaca cctacgatta catgaacggt cgggtggtgc ctccctcgct ggtggacgcc 1500
tacatcaaca tcggggcgcg ctggtcgctg gaccccatgg acaacgtcaa tcccttcaac 1560
caccaccgca acgcgggcct gcgctaccgc tccatgctcc tgggcaacgg gcgctacgtg 1620
cccttccaca tccaggtgcc ccagaaattt ttcgccatca agagcctcct gctcctgccc 1680
gggtcctaca cctacgagtg gaacttccgc aaggacgtca acatgatcct gcagagctcc 1740
ctcggcaacg acctgcgcac ggacggggcc tccatctcct tcaccagcat caacctctac 1800
gccaccttct tccccatggc gcacaacacg gcctccacgc tcgaggccat gctgcgcaac 1860
gacaccaacg accagtcctt caacgactac ctctcggcgg ccaacatgct ctaccccatc 1920
ccggccaacg ccaccaacgt gcccatctcc atcccctcgc gcaactgggc cgccttccgc 1980
ggctggtcct tcacgcgtct caagaccaag gagacgccct cgctgggctc cgggttcgac 2040
ccctacttcg tctactcggg ctccatcccc tacctcgacg gcaccttcta cctcaaccac 2100
accttcaaga aggtctccat caccttcgac tcctccgtca gctggcccgg caacgaccgg 2160
ctcctgacgc ccaacgagtt cgaaatcaag cgcaccgtcg acggcgaggg ctacaacgtg 2220
gcccagtgca acatgaccaa ggactggttc ctggtccaga tgctggccca ctacaacatc 2280
ggctaccagg gcttctacgt gcccgagggc tacaaggacc gcatgtactc cttcttccgc 2340
aacttccagc ccatgagccg ccaggtggtg gacgaggtca actacaagga ctaccaggcc 2400
gtcaccctgg cctaccagca caacaactcg ggcttcgtcg gctacctcgc gcccaccatg 2460
cgccaggggc agccctaccc cgccaactac ccgtacccgc tcatcggcaa gagcgccgtc 2520
accagcgtca cccagaaaaa gttcctctgc gacagggtca tgtggcgcat ccccttctcc 2580
agcaacttca tgtccatggg cgcgctcacc gacctcggcc agaacatgct ctatgccaac 2640
tccgcccacg cgctagacat gaatttcgaa gtcgacccca tggatgagtc cacccttctc 2700
tatgttgtct tcgaagtctt cgacgtcgtc cgagtgcacc agccccaccg cggcgtcatc 2760
gaggccgtct acctgcgcac acccttctcg gccggtaacg ccaccaccta a 2811
<210> 118
<211> 936
<212> PRT
<213> 黑猩猩腺病毒- ChAd 82六邻体
<400> 118
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Asn Glu Asn Asn Gly Gln Gly
130 135 140
Gln Ala Lys Thr His Thr Tyr Gly Val Ala Ala Met Gly Gly Leu Asp
145 150 155 160
Ile Thr Lys Glu Gly Leu Lys Ile Val Thr Asp Ala Ser Lys Glu Asp
165 170 175
Asp Asn Glu Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Ile
180 185 190
Gly Glu Glu Asn Trp Gln Asp Thr Lys Asn Phe Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Lys Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Arg
210 215 220
Pro Thr Asn Val Lys Gly Gly Gln Ala Lys Val Lys Thr Glu Glu Asn
225 230 235 240
Val Gln Ser Phe Asp Ile Asp Leu Ala Phe Phe Asp Ile Pro Ser Thr
245 250 255
Gly Thr Gly Gly Asn Gly Thr Asn Val Asn Asp Lys Pro Asp Met Val
260 265 270
Met Tyr Thr Glu Asn Val Asn Leu Glu Thr Pro Asp Thr His Ile Val
275 280 285
Tyr Lys Pro Gly Thr Ser Asp Asp Ser Ser Glu Ala Asn Leu Cys Gln
290 295 300
Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
305 310 315 320
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
325 330 335
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
340 345 350
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr
355 360 365
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
370 375 380
Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr
385 390 395 400
Cys Phe Pro Leu Asp Gly Ala Gly Thr Asn Ala Val Tyr Arg Gly Val
405 410 415
Lys Ala Lys Asp Asn Gly Asn Trp Glu Gln Asp Thr Gly Val Ser Ser
420 425 430
Ile Asn Gln Ile Cys Lys Gly Asn Ile Tyr Ala Met Glu Ile Asn Ile
435 440 445
Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn Val Ala Leu Tyr
450 455 460
Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr
465 470 475 480
Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Pro Pro Ser
485 490 495
Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro
500 505 510
Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg
515 520 525
Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile
530 535 540
Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro
545 550 555 560
Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile
565 570 575
Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile
580 585 590
Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His
595 600 605
Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp
610 615 620
Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile
625 630 635 640
Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp
645 650 655
Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr
660 665 670
Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser
675 680 685
Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys
690 695 700
Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg
705 710 715 720
Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu
725 730 735
Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val
740 745 750
Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro
755 760 765
Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro
770 775 780
Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala
785 790 795 800
Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu
805 810 815
Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr
820 825 830
Pro Leu Ile Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys Lys Phe
835 840 845
Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met
850 855 860
Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn
865 870 875 880
Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu
885 890 895
Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val
900 905 910
His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro
915 920 925
Phe Ser Ala Gly Asn Ala Thr Thr
930 935
<210> 119
<211> 933
<212> PRT
<213> 黑猩猩腺病毒- CV23 Pan5六邻体
<400> 119
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Asp Gly Asp Thr Gly
130 135 140
Thr Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser
145 150 155 160
Ile Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro
165 170 175
Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala
180 185 190
Glu Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys
210 215 220
Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly
225 230 235 240
Gly Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser
245 250 255
Ala Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn
260 265 270
Val Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr
275 280 285
Asp Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn
290 295 300
Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr
305 310 315 320
Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln
325 330 335
Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr
340 345 350
Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met
355 360 365
Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu
370 375 380
Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp
385 390 395 400
Ala Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Ala
405 410 415
Asp Gln Thr Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu
420 425 430
Leu Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn
435 440 445
Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp
450 455 460
Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn
465 470 475 480
Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp
485 490 495
Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn
500 505 510
Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser
515 520 525
Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro
530 535 540
Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr
545 550 555 560
Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser
565 570 575
Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr
580 585 590
Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala
595 600 605
Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe
610 615 620
Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn
625 630 635 640
Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe
645 650 655
Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu
660 665 670
Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr
675 680 685
Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile
690 695 700
Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr
705 710 715 720
Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn
725 730 735
Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu
740 745 750
Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr
755 760 765
Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg
770 775 780
Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu
785 790 795 800
Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr
805 810 815
Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile
820 825 830
Gly Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp
835 840 845
Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly
850 855 860
Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His
865 870 875 880
Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu
885 890 895
Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro
900 905 910
His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala
915 920 925
Gly Asn Ala Thr Thr
930
<210> 120
<211> 942
<212> PRT
<213> 黑猩猩腺病毒- CV32 Pan6六邻体
<400> 120
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asn Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Val Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Ser Gln Trp Glu Gln Ala Lys Thr Gly Asn Gly Gly
130 135 140
Thr Met Glu Thr His Thr Tyr Gly Val Ala Pro Met Gly Gly Glu Asn
145 150 155 160
Ile Thr Lys Asp Gly Leu Gln Ile Gly Thr Asp Val Thr Ala Asn Gln
165 170 175
Asn Lys Pro Ile Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Val
180 185 190
Gly Glu Glu Asn Trp Gln Glu Thr Glu Asn Phe Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Lys Asp Thr Asn Met Lys Pro Cys Tyr Gly Ser Tyr Ala Arg
210 215 220
Pro Thr Asn Glu Lys Gly Gly Gln Ala Lys Leu Lys Val Gly Asp Asp
225 230 235 240
Gly Val Pro Thr Lys Glu Phe Asp Ile Asp Leu Ala Phe Phe Asp Thr
245 250 255
Pro Gly Gly Thr Val Asn Gly Gln Asp Glu Tyr Lys Ala Asp Ile Val
260 265 270
Met Tyr Thr Glu Asn Thr Tyr Leu Glu Thr Pro Asp Thr His Val Val
275 280 285
Tyr Lys Pro Gly Lys Asp Asp Ala Ser Ser Glu Ile Asn Leu Val Gln
290 295 300
Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
305 310 315 320
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
325 330 335
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
340 345 350
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr
355 360 365
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
370 375 380
Val Arg Ile Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr
385 390 395 400
Cys Phe Pro Leu Asp Gly Ser Gly Thr Asn Ala Ala Tyr Gln Gly Val
405 410 415
Lys Val Lys Asp Gly Gln Asp Gly Asp Val Glu Ser Glu Trp Glu Asn
420 425 430
Asp Asp Thr Val Ala Ala Arg Asn Gln Leu Cys Lys Gly Asn Ile Phe
435 440 445
Ala Met Glu Ile Asn Leu Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr
450 455 460
Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Thr
465 470 475 480
Asn Val Thr Leu Pro Thr Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly
485 490 495
Arg Val Thr Pro Pro Ser Leu Val Asp Ala Tyr Leu Asn Ile Gly Ala
500 505 510
Arg Trp Ser Leu Asp Pro Met Asp Asn Val Asn Pro Phe Asn His His
515 520 525
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg
530 535 540
Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys
545 550 555 560
Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg
565 570 575
Lys Asp Val Asn Met Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg
580 585 590
Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr
595 600 605
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu
610 615 620
Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala
625 630 635 640
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
645 650 655
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg
660 665 670
Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr
675 680 685
Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu
690 695 700
Asn His Thr Phe Lys Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser
705 710 715 720
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
725 730 735
Arg Thr Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr
740 745 750
Lys Asp Trp Phe Leu Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr
755 760 765
Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe
770 775 780
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Val Asn
785 790 795 800
Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser
805 810 815
Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr
820 825 830
Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser
835 840 845
Val Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro
850 855 860
Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln
865 870 875 880
Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu
885 890 895
Val Asp Pro Met Asp Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val
900 905 910
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala
915 920 925
Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935 940
<210> 121
<211> 932
<212> PRT
<213> 黑猩猩腺病毒- CV33 Pan7六邻体
<400> 121
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Gly Asp Thr Asp Thr
130 135 140
Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Ser Ile
145 150 155 160
Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Ser Asp Gly Gln Ala Ile
165 170 175
Tyr Ala Asp Glu Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala Glu
180 185 190
Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala Leu
195 200 205
Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys Pro
210 215 220
Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Glu Thr Gly Gly
225 230 235 240
Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser Ala
245 250 255
Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn Val
260 265 270
Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr Asp
275 280 285
Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ser Met Pro Asn Arg
290 295 300
Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr
305 310 315 320
Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu
325 330 335
Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln
340 345 350
Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp
355 360 365
Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn
370 375 380
His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp Ala
385 390 395 400
Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Asp Asn
405 410 415
Gln Thr Thr Trp Thr Lys Asp Asp Thr Val Asn Asp Ala Asn Glu Leu
420 425 430
Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn Leu
435 440 445
Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp Ser
450 455 460
Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro Thr Asn Thr Asn Thr
465 470 475 480
Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp Ala
485 490 495
Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn Val
500 505 510
Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met
515 520 525
Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln
530 535 540
Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr Thr
545 550 555 560
Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Ser
565 570 575
Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ala Phe Thr Ser
580 585 590
Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser
595 600 605
Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn
610 615 620
Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala
625 630 635 640
Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg
645 650 655
Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu Thr Pro Ser Leu Gly
660 665 670
Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu
675 680 685
Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Thr
690 695 700
Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro
705 710 715 720
Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn Val
725 730 735
Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala
740 745 750
His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr Lys
755 760 765
Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln
770 775 780
Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu Ala
785 790 795 800
Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met
805 810 815
Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly
820 825 830
Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys Phe Leu Cys Asp Arg
835 840 845
Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala
850 855 860
Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala
865 870 875 880
Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu Leu
885 890 895
Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro His
900 905 910
Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly
915 920 925
Asn Ala Thr Thr
930
<210> 122
<211> 960
<212> PRT
<213> 黑猩猩腺病毒- ChAd 3六邻体
<400> 122
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135 140
Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu
145 150 155 160
Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu
165 170 175
Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala
180 185 190
Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro
195 200 205
Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val
210 215 220
Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr
225 230 235 240
Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu
245 250 255
Thr Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe
260 265 270
Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Ala Asn Asn Ile Gln Pro
275 280 285
Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr
290 295 300
His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile Met
305 310 315 320
Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
325 330 335
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
340 345 350
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
355 360 365
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly
370 375 380
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
385 390 395 400
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu
405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr
420 425 430
Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp
435 440 445
Thr Lys Asp Glu Thr Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn
450 455 460
Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe
465 470 475 480
Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn
485 490 495
Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met
500 505 510
Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu
515 520 525
Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn
530 535 540
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn
545 550 555 560
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
565 570 575
Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn
580 585 590
Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp
595 600 605
Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr
610 615 620
Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala
625 630 635 640
Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser
645 650 655
Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro
660 665 670
Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe
675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
690 695 700
Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe
705 710 715 720
Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser
725 730 735
Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu
740 745 750
Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn
755 760 765
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile
770 775 780
Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr
785 790 795 800
Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln
805 810 815
Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn
820 825 830
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln
835 840 845
Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val
850 855 860
Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg
865 870 875 880
Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu
885 890 895
Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr
900 905 910
Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe
915 920 925
Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
930 935 940
Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955 960
<210> 123
<211> 937
<212> PRT
<213> 黑猩猩腺病毒- ChAd 6六邻体
<400> 123
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Ser Gln Trp Ile Thr Lys Asp Asn Gly Thr Asp Lys
130 135 140
Thr Tyr Ser Phe Gly Asn Ala Pro Val Arg Gly Leu Asp Ile Thr Glu
145 150 155 160
Glu Gly Leu Gln Ile Gly Pro Asp Glu Ser Gly Gly Glu Ser Lys Lys
165 170 175
Ile Phe Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Leu Gly Asp Glu
180 185 190
Glu Trp His Asp Thr Ile Gly Ala Glu Asp Lys Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Pro Ala Thr Asn Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys
210 215 220
Pro Thr Asn Ala Lys Gly Gly Gln Ala Lys Ser Arg Thr Lys Asp Asp
225 230 235 240
Gly Thr Thr Glu Pro Asp Ile Asp Met Ala Phe Phe Asp Asp Arg Ser
245 250 255
Gln Gln Ala Ser Phe Ser Pro Glu Leu Val Leu Tyr Thr Glu Asn Val
260 265 270
Asp Leu Asp Thr Pro Asp Thr His Ile Ile Tyr Lys Pro Gly Thr Asp
275 280 285
Glu Thr Ser Ser Ser Phe Asn Leu Gly Gln Gln Ser Met Pro Asn Arg
290 295 300
Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr
305 310 315 320
Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu
325 330 335
Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln
340 345 350
Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp
355 360 365
Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn
370 375 380
His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Gly
385 390 395 400
Val Gly Phe Thr Asp Thr Phe Gln Gly Ile Lys Val Lys Thr Thr Asn
405 410 415
Asn Gly Thr Ala Asn Ala Thr Glu Trp Glu Ser Asp Thr Ser Val Asn
420 425 430
Asn Ala Asn Glu Ile Ala Lys Gly Asn Pro Phe Ala Met Glu Ile Asn
435 440 445
Ile Gln Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu
450 455 460
Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Ala Asn Ile Thr Leu Pro
465 470 475 480
Ala Asn Thr Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro
485 490 495
Ser Leu Val Asp Ala Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp
500 505 510
Pro Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu
515 520 525
Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His
530 535 540
Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu
545 550 555 560
Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met
565 570 575
Ile Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser
580 585 590
Ile Ala Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala
595 600 605
His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn
610 615 620
Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro
625 630 635 640
Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn
645 650 655
Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Arg Glu
660 665 670
Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly
675 680 685
Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys
690 695 700
Lys Val Ser Ile Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp
705 710 715 720
Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly
725 730 735
Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu
740 745 750
Val Gln Met Leu Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val
755 760 765
Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln
770 775 780
Pro Met Ser Arg Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln
785 790 795 800
Ala Val Thr Leu Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr
805 810 815
Leu Ala Pro Thr Met Arg Gln Gly Gln Pro Tyr Pro Ala Asn Tyr Pro
820 825 830
Tyr Pro Leu Ile Gly Lys Ser Ala Val Ala Ser Val Thr Gln Lys Lys
835 840 845
Phe Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe
850 855 860
Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala
865 870 875 880
Asn Ser Ala His Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp
885 890 895
Glu Ser Thr Leu Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg
900 905 910
Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg Thr
915 920 925
Pro Phe Ser Ala Gly Asn Ala Thr Thr
930 935
<210> 124
<211> 956
<212> PRT
<213> 黑猩猩腺病毒- C1六邻体
<400> 124
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Asn Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Met Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Phe Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Ser Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Ser Gln Trp Leu Asp Lys Gly Val Thr Thr Thr Asp
130 135 140
Asn Asn Thr Glu Asn Gly Asp Glu Glu Asp Glu Val Ala Glu Glu Gly
145 150 155 160
Glu Glu Glu Lys Gln Ala Thr Tyr Thr Phe Gly Asn Ala Pro Val Lys
165 170 175
Ala Glu Ala Glu Ile Thr Lys Glu Gly Leu Pro Ile Gly Leu Glu Val
180 185 190
Pro Ser Glu Gly Asp Pro Lys Pro Ile Tyr Ala Asp Lys Leu Tyr Gln
195 200 205
Pro Glu Pro Gln Val Gly Glu Glu Ser Trp Thr Asp Thr Asp Gly Thr
210 215 220
Asp Glu Lys Tyr Gly Gly Arg Ala Leu Lys Pro Glu Thr Lys Met Lys
225 230 235 240
Pro Cys Tyr Gly Ser Phe Ala Lys Pro Thr Asn Val Lys Gly Gly Gln
245 250 255
Ala Lys Val Lys Lys Val Glu Glu Gly Lys Val Glu Tyr Asp Ile Asp
260 265 270
Met Asn Phe Phe Asp Leu Arg Ser Gln Lys Thr Gly Leu Lys Pro Lys
275 280 285
Ile Val Met Tyr Ala Glu Asn Val Asp Leu Glu Thr Pro Asp Thr His
290 295 300
Val Val Tyr Lys Pro Gly Ala Ser Asp Ala Ser Ser His Ala Asn Leu
305 310 315 320
Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp
325 330 335
Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val
340 345 350
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp
355 360 365
Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Leu Gly Asp
370 375 380
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp
385 390 395 400
Pro Asp Val Arg Val Ile Glu Asn His Gly Val Glu Asp Glu Leu Pro
405 410 415
Asn Tyr Cys Phe Pro Leu Asp Gly Val Gly Pro Arg Thr Asp Ser Tyr
420 425 430
Lys Gly Ile Glu Thr Asn Gly Asp Glu Asn Thr Thr Trp Lys Asp Leu
435 440 445
Asp Pro Asn Gly Ile Ser Glu Leu Ala Lys Gly Asn Pro Phe Ala Met
450 455 460
Glu Ile Asn Ile Gln Ala Asn Leu Trp Arg Ser Phe Leu Tyr Ser Asn
465 470 475 480
Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro Thr Asn Val
485 490 495
Thr Leu Pro Glu Asn Lys Asn Thr Tyr Asp Tyr Met Asn Gly Arg Val
500 505 510
Val Pro Pro Ser Leu Val Asp Thr Tyr Val Asn Ile Gly Ala Arg Trp
515 520 525
Ser Leu Asp Ala Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn
530 535 540
Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val
545 550 555 560
Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Val Lys Asn Leu
565 570 575
Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp
580 585 590
Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp
595 600 605
Gly Ala Ser Ile Ser Phe Thr Ser Ile Asn Leu Tyr Ala Thr Phe Phe
610 615 620
Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
625 630 635 640
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met
645 650 655
Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro
660 665 670
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu Lys
675 680 685
Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val
690 695 700
Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
705 710 715 720
Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val Ser Trp Pro
725 730 735
Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Thr
740 745 750
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp
755 760 765
Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly
770 775 780
Phe Tyr Val Pro Glu Gly Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg
785 790 795 800
Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Glu Ile Asn Tyr Lys
805 810 815
Asp Tyr Lys Ala Val Ala Val Pro Tyr Gln His Asn Asn Ser Gly Phe
820 825 830
Val Gly Tyr Met Ala Pro Thr Met Arg Gln Gly Gln Ala Tyr Pro Ala
835 840 845
Asn Tyr Pro Tyr Pro Leu Ile Gly Thr Thr Ala Val Thr Ser Val Thr
850 855 860
Gln Lys Lys Phe Leu Cys Asp Arg Thr Met Trp Arg Ile Pro Phe Ser
865 870 875 880
Ser Asn Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu
885 890 895
Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp
900 905 910
Pro Met Asp Glu Pro Thr Leu Leu Tyr Leu Leu Phe Glu Val Phe Asp
915 920 925
Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr
930 935 940
Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955
<210> 125
<211> 933
<212> PRT
<213> 黑猩猩腺病毒- CV68六邻体
<400> 125
Met Ala Thr Pro Ser Met Leu Pro Gln Trp Ala Tyr Met His Ile Ala
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Asn Thr Tyr Ser Tyr
65 70 75 80
Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Thr Cys Gln Trp Thr Tyr Lys Ala Asp Gly Glu Thr Ala
130 135 140
Thr Glu Lys Thr Tyr Thr Tyr Gly Asn Ala Pro Val Gln Gly Ile Asn
145 150 155 160
Ile Thr Lys Asp Gly Ile Gln Leu Gly Thr Asp Thr Asp Asp Gln Pro
165 170 175
Ile Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro Gln Val Gly Asp Ala
180 185 190
Glu Trp His Asp Ile Thr Gly Thr Asp Glu Lys Tyr Gly Gly Arg Ala
195 200 205
Leu Lys Pro Asp Thr Lys Met Lys Pro Cys Tyr Gly Ser Phe Ala Lys
210 215 220
Pro Thr Asn Lys Glu Gly Gly Gln Ala Asn Val Lys Thr Gly Thr Gly
225 230 235 240
Thr Thr Lys Glu Tyr Asp Ile Asp Met Ala Phe Phe Asp Asn Arg Ser
245 250 255
Ala Ala Ala Ala Gly Leu Ala Pro Glu Ile Val Leu Tyr Thr Glu Asn
260 265 270
Val Asp Leu Glu Thr Pro Asp Thr His Ile Val Tyr Lys Ala Gly Thr
275 280 285
Asp Asp Ser Ser Ser Ser Ile Asn Leu Gly Gln Gln Ala Met Pro Asn
290 295 300
Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr
305 310 315 320
Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln
325 330 335
Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr
340 345 350
Gln Leu Leu Leu Asp Ser Leu Gly Asp Arg Thr Arg Tyr Phe Ser Met
355 360 365
Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu
370 375 380
Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asp
385 390 395 400
Ala Val Gly Arg Thr Asp Thr Tyr Gln Gly Ile Lys Ala Asn Gly Thr
405 410 415
Asp Gln Thr Thr Trp Thr Lys Asp Asp Ser Val Asn Asp Ala Asn Glu
420 425 430
Ile Gly Lys Gly Asn Pro Phe Ala Met Glu Ile Asn Ile Gln Ala Asn
435 440 445
Leu Trp Arg Asn Phe Leu Tyr Ala Asn Val Ala Leu Tyr Leu Pro Asp
450 455 460
Ser Tyr Lys Tyr Thr Pro Ala Asn Val Thr Leu Pro Thr Asn Thr Asn
465 470 475 480
Thr Tyr Asp Tyr Met Asn Gly Arg Val Val Ala Pro Ser Leu Val Asp
485 490 495
Ser Tyr Ile Asn Ile Gly Ala Arg Trp Ser Leu Asp Pro Met Asp Asn
500 505 510
Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser
515 520 525
Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro
530 535 540
Gln Lys Phe Phe Ala Ile Lys Ser Leu Leu Leu Leu Pro Gly Ser Tyr
545 550 555 560
Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser
565 570 575
Ser Leu Gly Asn Asp Leu Arg Thr Asp Gly Ala Ser Ile Ser Phe Thr
580 585 590
Ser Ile Asn Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala
595 600 605
Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe
610 615 620
Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn
625 630 635 640
Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe
645 650 655
Arg Gly Trp Ser Phe Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu
660 665 670
Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr
675 680 685
Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile
690 695 700
Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr
705 710 715 720
Pro Asn Glu Phe Glu Ile Lys Arg Thr Val Asp Gly Glu Gly Tyr Asn
725 730 735
Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu
740 745 750
Ala His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Gly Tyr
755 760 765
Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg
770 775 780
Gln Val Val Asp Glu Val Asn Tyr Lys Asp Tyr Gln Ala Val Thr Leu
785 790 795 800
Ala Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr
805 810 815
Met Arg Gln Gly Gln Pro Tyr Pro Ala Xaa Tyr Pro Tyr Pro Leu Ile
820 825 830
Gly Lys Ser Ala Val Thr Ser Val Thr Gln Lys Lys Phe Leu Cys Asp
835 840 845
Arg Val Met Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly
850 855 860
Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His
865 870 875 880
Ala Leu Asp Met Asn Phe Glu Val Asp Pro Met Asp Glu Ser Thr Leu
885 890 895
Leu Tyr Val Val Phe Glu Val Phe Asp Val Val Arg Val His Gln Pro
900 905 910
His Arg Gly Val Ile Glu Ala Val Tyr Xaa Arg Thr Pro Phe Ser Ala
915 920 925
Gly Asn Ala Thr Thr
930

Claims (10)

1.分离的重组黑猩猩血清型,包含选自下组的六邻体和纤维核酸序列的任何组合:
a)选自由SEQ ID NO:16-25、41、43、97、99、101、103、105、107、109、111、113、115和117构成的组的六邻体基因序列;和
b)选自由SEQ ID NO:6-15、42、44、58、60、62、64、66、68、70、72、74、76和78构成的组的纤维基因序列。
2.一种分离的重组黑猩猩血清型,包含来源于腺病毒的六邻体和纤维核酸序列的任何组合,所述腺病毒选自由ECACC登记号03121201(ChAd4)、03121202(ChAd5)、03121203(ChAd7)、03121204(ChAd9)、03121205(ChAd10)、03121206(ChAd11)、03121207(ChAd16)、03121208(ChAd17)、03121209(ChAd19)和03121210(ChAd20)构成的分离物的组。
3.一种复制缺陷性黑猩猩腺病毒(ChAd)载体,包含来源于腺病毒的核苷酸序列,所述腺病毒选自由ECACC登记号03121201(ChAd4)、03121202(ChAd5)、03121203(ChAd7)、03121204(ChAd9)、03121205(ChAd10)、03121206(ChAd11)、03121207(ChAd16)、03121208(ChAd17)、03121209(ChAd19)和03121210(ChAd20)构成的分离物的组,和与调节序列可操作连接的编码至少一个免疫原的转基因,所述调节序列指导所述转基因在哺乳动物细胞中的表达,其中所述载体缺少包含选自由腺病毒E1、E2、E3和E4构成的组的至少一个腺病毒基因的核苷酸。
4.一种复制缺陷性黑猩猩腺病毒(ChAd)载体,包含在SEQ ID NO:1或SEQ ID NO:2中列出的核苷酸序列,和与调节序列可操作连接的编码至少一个免疫原的转基因,所述调节序列指导所述转基因在哺乳动物细胞中的表达,其中所述载体缺少SEQ ID NO:1或SEQ IDNO:2的核苷酸序列,所述核苷酸序列包含选自由腺病毒E1、E2、E3和E4构成的组的至少一个基因。
5.一种复制缺陷性ChAd载体,其包含在SEQ ID NO:1的bp 460到bp 3542、或SEQ IDNO:2的bp 457到bp 3425的区域中、在E1核苷酸序列中的删除/破坏。
6. 一种宿主细胞,包含根据权利要求1的核酸分子,其中所述宿主细胞表达选自由E1a、E1b、E2a、E2b、E4 orfs 1、2、3、4、5、6、6/7、pIX、IVa2、区域L1、L2、L3、L4、L5构成的组的一种或多种腺病毒区域。
7.生产复制缺陷性黑猩猩腺病毒载体的方法,包括将根据权利要求4的腺病毒载体导入表达腺病毒E-1的人类细胞,并收获产生的腺病毒。
8.一种疫苗组合物,包含根据权利要求3-5的任何一个的复制缺陷性ChAd载体。
9.在哺乳动物中强化抗原特异性免疫反应的方法,包括向所述哺乳动物施用足够量的重组ChAd载体,其包含含有其E1基因的至少功能性删除的黑猩猩腺病毒基因组、编码目标抗原的核苷酸序列和能指导编码所述目标抗原的所述核苷酸序列的表达的启动子序列,其中施用所述chAd载体引发强化的反应。
10.在幼稚哺乳动物中引发免疫反应的方法,包括向所述哺乳动物施用足够量的ChAd载体,其包含含有其E1基因的至少功能性删除的黑猩猩腺病毒基因组、编码目标抗原的核苷酸和能指导编码所述目标抗原的所述核苷酸序列的表达的启动子序列,其中施用所述chAd载体引发初级免疫反应。
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