CN115340998B - 一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗及其应用 - Google Patents
一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗及其应用 Download PDFInfo
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Abstract
本发明公开了一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗及其应用。所述重组病毒载体以变异型相关病毒AAV‑ie为骨架,并包含编码新冠病毒S1蛋白的核苷酸片段;其中:所述变异型相关病毒AAV‑ie的衣壳蛋白相比于野生型AAV‑DJ衣壳蛋白VP1,在N589和R590之间插入氨基酸片段,所述氨基酸片段的氨基酸序列如SEQ ID NO:7所示。本发明获得的所述新冠病毒疫苗对于野生型以及B.1.1.7,B.1.351等突变体病毒均具有很好的免疫效果。
Description
技术领域
本发明属于新冠病毒疫苗领域,具体涉及一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗(命名为AAV-ie-S1疫苗)及其应用,并提供了一种疫苗制备方法。
背景技术
新冠病毒由四个结构蛋白组成,分别是刺突蛋白(spike,S)、包膜蛋白(envelope,E)、膜蛋白/基质蛋白(membrane/matrix,M)和核衣壳蛋白(nucleocapsid,N)。S蛋白中的S1结构域包括受体结合区(receptor bingding domain,RBD)和NTD结构区域。RBD能够与人体细胞的血管紧张素转化酶2受体(ACE2)结合,介导了新冠病毒进入宿主细胞。因此,针对S蛋白的中和抗体可以阻断新冠病毒侵入宿主细胞,所以目前在研究的大多数新冠疫苗都是以全长S蛋白为主要抗原进行设计开发的。针对其他部分或者S蛋白的结构域的设计的疫苗较少。
目前,已经上市的新冠病毒疫苗包括灭活疫苗、mRNA疫苗、腺病毒疫苗以及重组蛋白疫苗。这些疫苗的技术路线大多采用S蛋白全长作为免疫原。而且,这些技术路线各有优劣。1)灭活疫苗生产工艺要求较高,需要生物安全等级3级以上的生产车间,限制了产能并增加了生产成本;2)mRNA疫苗是第一次在疫苗领域被应用,其安全性、可靠性等仍需要时间来检验,而且,其需要低温储存,不利于疫苗的长距离运输,也增加了成本;3)腺病毒疫苗存在免疫原性的问题;4)重组蛋白疫苗成本相对较高,而且免疫效果的持久性不如其他疫苗。此外,新的病毒突变株的出现,同样对现有疫苗的疗效提出了巨大的挑战。已有研究表明,目前出现的B.1.351病毒株,对已开发的疫苗产生了免疫逃逸,疫苗的保护效率大大降低。基于此,开发新的疫苗技术路线对于新冠病毒的预防有重要意义,也提供了疫苗策略更多的选择性。
腺相关病毒(AAV)是一类现阶段广泛应用的基因治疗载体,基于此载体的两款基因治疗产品已被美国FDA批准上市,证明了AAV载体的安全性和有效性。AAV相较于其他疫苗所用的技术路线具有表达持续时间长、载体本身免疫原性低以及容易大量制备等特点,因此,也是制备疫苗的可选方案。基于已有专利(具有变异衣壳蛋白的腺相关病毒及其用途,申请号:CN110437317A),该专利中AAV-ie具有广泛感染的特性。利用AAV-ie包裹表达新冠病毒S1蛋白的DNA元件,纯化后作为新冠疫苗,数据显示该疫苗具有很好的免疫原性,能够高效诱导新冠病毒中和抗体,激活抗原特异性的T细胞免疫,并对出现的变异病毒株具有很好的中和活性,不会产生免疫逃逸。
发明内容
本发明所要解决的技术问题是为克服现有技术中缺乏有效的新冠病毒疫苗的缺陷,提供一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗及其应用。
本发明主要通过如下技术方案解决上述技术问题。
本发明的技术方案之一为:一种重组病毒载体,其以变异型相关病毒AAV-ie为骨架,并包含编码新冠病毒S1蛋白的核苷酸片段;其中:所述变异型相关病毒AAV-ie的衣壳蛋白相比于野生型AAV-DJ衣壳蛋白VP1,在N589和R590之间插入氨基酸片段,所述氨基酸片段的氨基酸序列如SEQ ID NO:7所示。
在本发明一优选实施方案中,所述变异型相关病毒AAV-ie的衣壳蛋白的氨基酸序列如SEQ ID NO:4所示。
在本发明一具体实施方案中,所述的重组病毒载体包含如SEQ ID NO:5所示的序列。
在本发明一具体实施方案中,所述新冠病毒S1蛋白的氨基酸序列如SEQ ID NO:2所示;编码所述新冠病毒S1蛋白的核苷酸序列优选如SEQ ID NO:1所示。
本发明的技术方案之二为:一种重组病毒,其包含如技术方案之一所述的重组病毒载体。
在本发明一优选实施方案中,所述重组病毒的制备方法包括:将pHelper质粒、AAV-ie Rep-Cap辅助包装质粒以及如技术方案之一所述的重组病毒载体转染HEK 293T细胞后进行培养;所述转染优选通过磷酸钙进行。
以上所述的pHelper质粒可为本领域常规的pHelper质粒。
在本发明一具体实施方案中,所述AAV-ie Rep-Cap辅助包装质粒含有如SEQ IDNO:3所示的序列。
本发明的技术方案之三为:一种新冠病毒疫苗,其包含如技术方案之二所述的重组病毒。
本发明的技术方案之四为:一种套装药盒,其包含如技术方案之一所述的重组病毒载体、如技术方案之二所述的重组病毒或者如技术方案之三所述的新冠病毒疫苗。
本发明的技术方案之五为:如技术方案之一所述的重组病毒载体或者如技术方案之二所述的重组病毒在制备新冠病毒疫苗中的应用。
本发明的技术方案之六为:一种递送装置,其含有如技术方案之三所述的新冠病毒疫苗;
所述装置包括:容器、密封件和注射针头;
其中:
所述的容器优选为管形瓶、注射器;
所述的密封件优选为密封塞或密封圈;
所述的注射针头优选为水针或单针-微针组。
本发明的技术方案之七为:一种新冠病毒疫苗的制备方法,所述制备方法包括:将pHelper质粒、AAV-ie Rep-Cap辅助包装质粒以及如技术方案之一所述的重组病毒载体转染哺乳动物细胞后进行培养。
所述哺乳动物细胞优选HEK 293T细胞。
对于AAV-ie Rep-Cap辅助包装质粒的优选限定同技术方案之二。
在符合本领域常识的基础上,上述各优选条件,可任意组合,即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于:
本发明鉴定出S1蛋白的抗原效果比Spike全长和RBD聚体产生免疫原性的效果好,并将其与AAV-ie相结合,所得疫苗能对野生型以及B.1.1.7和B.1.351两种突变体病毒有明显的免疫效果。
附图说明
图1为疫苗表达S1蛋白,用蛋白免疫印迹的方法检测。
图2为AAV-ie包裹EGFP注射肌肉后,EGFP在各组织中的表达情况。
图3为AAV-ie包装的不同抗原注射小鼠肌肉后,抗体产生的滴度。
图4为AAV-ie-S1疫苗在注射小鼠后不同天数的血清对新冠假病毒的中和实验。
图5为AAV-ie-S1疫苗在注射猴子后不同天数的血清中检测抗体产生的滴度。
图6为AAV-ie-S1疫苗在注射猴子后不同天数的血清对新冠假病毒的中和实验。
图7为AAV-ie-S1疫苗在注射猴子后不同天数的T细胞免疫反应检测。
图8为AAV-ie-S1疫苗在注射猴子后不同天数的血清对野生型和两种突变病毒的新冠假病毒的中和实验。
具体实施方式
下面通过实施例的方式进一步说明本发明,但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法,按照常规方法和条件,或按照商品说明书选择。
实施例1 AAV-ie-S1病毒感染293T后能表达S1蛋白
AAV-ie-S1病毒的包装纯化具体如下:
本实验涉及到的病毒均使用HEK 293T细胞(购自ATCC)生产,用碘沙醇梯度纯化法进行纯化。实验使用三质粒共转的方法,将pHelper、AAV-ie Rep-Cap辅助包装质粒(SEQ IDNO:3)以及内含物质粒pAAV-CMV-S1-His(SEQ ID NO:5)一起通过磷酸钙转染进入HEK 293T细胞。其中S1蛋白的氨基酸序列如SEQ ID NO:2所示,核苷酸序列如SEQ ID NO:1所示。转染后48h收全部上清到50mL离心管,4℃储存,加入新鲜的DMEM培养基(hyClone公司)和胎牛血清(hyClone公司),继续培养。转染后96h,用枪头轻轻吹下细胞,收集所有的细胞到50mL高速离心管。取细胞时注意手套和枪的清洁,避免交叉污染。将初次收集的培养基离心3000rpm 10min,取上清到200mL容量瓶,将少量沉淀的细胞加入第二次收集的培养基中。在通风橱中向第二次收集的培养基中加3~5mL氯仿(Titan公司),此时会看到液体分上下两层。将离心管放37℃摇床1h。向装有第一次收集的上清的容量瓶中加总体积(两次收集的上清之和加上10mL,加入PEG后体积会增大)10%(M/V)PEG 8000(上海生工),1M NaCl(ABcone公司),摇匀。离心管配平,13000rpm离心15~30min,取上清(弃氯仿和沉淀),加到储存上清的容量瓶中。离心后,用含有Dnase I(Thermo)和Rnase A(天根生物)的PBS缓冲液将病毒颗粒重悬。使用15%、25%、40%和60%碘克沙醇(Sigma-Aldrich)溶液进行分层,然后将产生的病毒悬浮液覆盖。10℃,350000g离心90min。超速离心法后,收集40%碘克沙醇层处的AAV,交换缓冲区以去除碘克沙醇,浓缩提纯的病毒。
将AAV-ie-S1病毒包装纯化后,感染293T(购自ATCC),72小时后收集细胞培养上清,用His tag的抗体(购自Proteintech公司,货号:66005-1-Ig)做蛋白免疫印迹,能检测到S1蛋白的表达(图1)。
实施例2 AAV-ie腺相关病毒能够高效感染小鼠大腿外侧骨骼肌
AAV-ie包装荧光蛋白EGFP:
包装步骤同实施例1中的方法,本实验涉及到的病毒均使用HEK 293T细胞(来源于ATCC公司)生产,用碘沙醇梯度纯化法进行纯化。实验使用三质粒共转的方法,将病毒血清型载体质粒、Rep-Cap辅助包装质粒以及内含物质粒pAAV-CMV-EGFP(SEQ ID NO:6)一起通过磷酸钙转染进入HEK293T细胞。转染后48h收全部上清到50mL离心管,4℃储存,加入新鲜的DMEM培养基(hyClone公司)和胎牛血清(hyClone公司),继续培养。转染后96h(根据不同的病毒调整时间),用枪头轻轻吹下细胞,收集所有的细胞到50mL高速离心管。取细胞时注意手套和枪的清洁,避免交叉污染。将初次收集的培养基离心3000rpm 10min,取上清到200mL容量瓶,将少量沉淀的细胞加入第二次收集的培养基中。在通风橱中向第二次收集的培养基中加3~5mL氯仿(Titan公司),此时会看到液体分上下两层。将离心管放37℃摇床1h。向装有第一次收集的上清的容量瓶中加总体积(两次收集的上清之和加上10mL,加入PEG后体积会增大)10%(M/V)PEG 8000(上海生工),1M NaCl(ABcone公司),摇匀。离心管配平,13000rpm离心15~30min,取上清(弃氯仿和沉淀),加到储存上清的容量瓶中。离心后,用含有Dnase I(Thermo)和Rnase A(天根生物)的PBS缓冲液将病毒颗粒重悬。使用15%、25%、40%和60%碘克沙醇(Sigma-Aldrich)溶液进行分层,然后将产生的病毒悬浮液覆盖。10℃,350000g离心90min。超速离心法后,收集40%碘克沙醇层处的AAV,交换缓冲区以去除碘克沙醇,浓缩提纯的病毒。
之后,以6E10 GC的病毒量注射BALB/c鼠(购自上海杰思捷实验动物有限公司)腿部外侧骨骼肌,一个月后,取腿部外侧骨骼肌和全身各处其他组织,观察AAV-ie病毒的感染情况。结果显示,AAV-ie只感染注射部位的肌肉组织,不感染其他组织(图2)。
显示出高度的特异性和安全性。图中绿色的为EGFP荧光蛋白,蓝色的为细胞核的标记DAPI染色。
实施例3 AAV-ie-S1疫苗注射小鼠腿部肌肉后能产生高滴度的抗体
左手抓好动物,露出需要注射的腿部,防止剧烈挣扎;另外一人用左手拇指和终止轻轻拉住小鼠的腿部,食指轻轻托起,右手注射,注意注射时下针的角度(30度左右)。注射剂量为100微升。注射要缓慢、稳定。注射完成后用手指或者棉签按压注射部位片刻,防止出血。注射完毕,放回鼠笼。2个月后,眼眶取血,制备血清,用10微升的毛细管,垂直插入内眦并向眼底方向转动以便切开静脉丛,血液便会连续不断地滴入采血管。血液凝集后离心取血清。利用Elisa试验测定抗体的含量。将Elisa板以2μg/mL浓度的spike蛋白在4℃包被过夜。次日以PBS清洗3此,继而以3%的BSA在室温封闭2小时。加入梯度稀释的小鼠血清,室温孵育2小时,PBS清洗3次。清洗后加入HRP偶联的goat anti-mouse IgG(Proteintech)作为二抗,孵育1小时后,以PBS清洗,加入TMB底物(Beyotime)显色10分钟,加入10%H2SO4终止反应。使用酶标仪检测450nm处吸光度。使用prizm软件拟合浓度梯度曲线,以信号为背景信号4倍处的稀释比例作为抗体滴度。结果如图3所示,与对照组相比,比较三种抗原免疫产生抗体的能力,AAV-ie-S1疫苗所携带的S1抗原产生IgG2a和IgG1抗体的能力高于RBD-Trimer和Spike全长。注射的病毒量均为每只鼠6E10 GC。
实施例4 AAV-ie-S1疫苗免疫小鼠后,血清对新冠假病毒的中和能力
在小鼠注射疫苗后不同的时间,取血清,在细胞水平上,用新冠假病毒测试免疫产生的抗体对病毒的抑制作用。将稳定表达ACE2受体的293T细胞以5000个细胞/孔密度种在96孔板中。24小时后,将免疫后的小鼠血清与实验室自制的新冠假病毒混合,室温孵育1小时,加入96孔板中。培养过夜后,将细胞培养板中上清去除,更换为新鲜的细胞培养基。该假病毒表面表达新冠病毒Spike蛋白,并且基因组中携带荧光素酶报告基因,当血清中有新冠病毒Spike蛋白的抗体,就能阻止新冠假病毒感染细胞表达荧光素酶报告基因。48小时后将细胞裂解,用Firefly luciferase Assay Kit(promege)检测luciferase的表达,并进一步计算血清中和假病毒的EC50值。如图4,不同周数取的血清能很好的抑制病毒对细胞的侵染。
实施例5 AAV-ie-S1疫苗注射猴子腿部肌肉后能产生高滴度的抗体
固定成年猕猴(rhesus macaque)使其勿活动,将手臂注射部位被毛剪去,右手持注射器,使注射器与肌肉成60°角,一次刺入肌肉中,为防止药物进人血管,注药液之前要回抽针栓,如无回血则可注药,注射完毕后用手轻轻按摩注射部位,帮助药液吸收。用5~6号针头注射,注射1E13 GC的病毒量,注射体积为750微升的疫苗后,在不同时间取猕猴(rhesus macaque)外周血制备血清,用ELISA方法检测结合S蛋白的抗体滴度。方法如实施例3,将Elisa板以2μg/mL浓度的spike蛋白在4℃包被过夜。次日以PBS清洗3此,继而以3%的BSA在室温封闭2小时。加入梯度稀释的小鼠血清,室温孵育2小时,PBS清洗3次。清洗后加入HRP偶联的goat anti-human IgG(Proteintech)作为二抗,孵育1小时后,以PBS清洗,加入TMB底物显色10分钟,加入10%H2SO4终止反应。使用酶标仪检测450nm处吸光度。使用prizm软件拟合浓度梯度曲线,以信号为背景信号4倍处的稀释比例作为抗体滴度。结果如图5所示,免疫4周后抗体滴度达到峰值并在后续检测中维持稳定。AAV-ie-eGFP作为对照组,注射后不能有效诱导特异性抗体的产生。
实施例6 AAV-ie-S1疫苗免疫猴子后,血清对新冠假病毒的中和能力
实验方法如实施例4。将稳定表达ACE2受体的293T细胞以5000个细胞/孔密度种在96孔板中。24小时后,将免疫后的猴血清与假病毒混合,室温孵育1小时,加入96孔板中。培养过夜后,将细胞培养板中上清去除,更换为新鲜的细胞培养基。48小时后,将细胞裂解,检测细胞内荧光素酶报告基因的表达。并计算EC50。结果如图6所示,AAV-ie-S1免疫后的血清能够有效中和新冠假病毒,相应的,AAV-ie-eGFP作为对照组,注射后不能有效诱导中和抗体的产生。
实施例7 AAV-ie-S1疫苗能够引起特异性的T细胞反应
取接种疫苗前(第0周)和接种后(第8周)的猕猴外周血,使用Ficoll分离外周血单核细胞(PBMC),培养于含10%FBS的RPMI 1640培养基(Gibco)中,将PBMC细胞使用S肽库(金斯瑞)刺激6小时,同时加入外泌抑制剂Brefeldin A(MCE)。细胞以PBS清洗后,使用Live/dead染料染色去除死细胞。继而使用pacific blue偶联的anti-human CD3(BD)、FITC偶联的anti-human CD4(BD)、PE偶联的anti-human CD8(BD)抗体染色。使用4%PFA将细胞固定,进一步使用0.3%Triton X100处理细胞30分钟。使用APC偶联的anti-human IFNγ或anti-human IL2或anti-human TNFα(BD)进行胞内染色。并使用流式细胞仪进行分析。结果如图7所示,与免疫前相比,免疫8周后的PBMC细胞,使用S肽库刺激后,CD4+T细胞中的IFNγ+,IL2+和TNFα+群体上调。同时CD8+T细胞的IFNγ+,IL2+和TNFα+群体上调。这些结果表明,AAV-ie-S1在疫苗接种后能够诱导S蛋白特异性的T细胞免疫应答。
实施例8 AAV-ie-S1对新冠病毒突变株具有良好的免疫活性
检测AAV-ie-S1免疫后的小鼠血清及猴子血清对最新出现的新冠变体B.1.351和B.1.1.7的假病毒中和活性。具体实施方法如实施例4,将稳定表达ACE2受体的293T细胞以5000个细胞/孔密度种在96孔板中。24小时后,将免疫后的小鼠或猴血清与假病毒混合,室温孵育1小时,加入96孔板中。培养过夜后,更换为新鲜的细胞培养基。48小时后,将细胞裂解,检测细胞内荧光素酶报告基因的表达。并计算EC50。结果如图8所示,小鼠免疫血清对B.1.351的中和活性未见明显下降,同时对B.1.1.7的中和活性上升。与之类似,猴子免疫血清对B.1.351的中和活性也未见明显下降,同时对B.1.1.7的中和活性上升。
SEQUENCE LISTING
<110> 上海科技大学
<120> 一种重组病毒载体、包含其的重组病毒、新冠病毒疫苗及其应用
<130> P21014084C
<160> 7
<170> PatentIn version 3.5
<210> 1
<211> 2016
<212> DNA
<213> SARS-CoV-2
<400> 1
cagtgcgtga acctgaccac aaggacccag ctgccccctg cctataccaa ttccttcaca 60
cggggcgtgt actatcccga caaggtgttt agaagctccg tgctgcactc tacacaggat 120
ctgtttctgc ctttctttag caacgtgacc tggttccacg ccatccacgt gagcggcacc 180
aatggcacaa agcggttcga caatccagtg ctgcccttta acgatggcgt gtacttcgcc 240
tctaccgaga agagcaacat catcagaggc tggatctttg gcaccacact ggactccaag 300
acacagtctc tgctgatcgt gaacaatgcc accaacgtcg tgatcaaggt gtgcgagttc 360
cagttttgta atgatccttt cctgggcgtg tactatcaca agaacaataa gagctggatg 420
gagtccgagt ttcgcgtgta ttctagcgcc aacaattgca catttgagta cgtgtcccag 480
ccattcctga tggacctgga gggcaagcag ggcaatttca agaacctgag ggagttcgtg 540
tttaagaata tcgatggcta cttcaagatc tactctaagc acaccccaat caacctggtg 600
cgcgacctgc cacagggctt cagcgccctg gagccactgg tggatctgcc catcggcatc 660
aacatcaccc ggtttcagac actgctggcc ctgcacagaa gctacctgac acctggcgac 720
tcctctagcg gatggaccgc aggagctgcc gcctactatg tgggctatct gcagccaagg 780
accttcctgc tgaagtacaa cgagaatggc accatcacag acgcagtgga ttgcgcactg 840
gaccccctga gcgagaccaa gtgtacactg aagtccttta ccgtggagaa gggcatctat 900
cagacatcca atttcagggt gcagcccacc gagtctatcg tgcgctttcc caatatcaca 960
aacctgtgcc cttttggcga ggtgttcaac gcaaccaggt tcgcaagcgt gtacgcatgg 1020
aataggaagc ggatcagcaa ctgcgtggcc gactatagcg tgctgtacaa ctccgcctct 1080
ttcagcacct ttaagtgcta tggcgtgtcc cccacaaagc tgaatgacct gtgctttacc 1140
aacgtgtacg ccgattcttt cgtgatcagg ggcgacgagg tgcgccagat cgcaccagga 1200
cagacaggca agatcgcaga ctacaattat aagctgcctg acgatttcac cggctgcgtg 1260
atcgcctgga acagcaacaa tctggattcc aaagtgggcg gcaactacaa ttatctgtac 1320
cggctgttta gaaagtctaa tctgaagcca ttcgagaggg acatctctac agagatctac 1380
caggcaggca gcaccccatg caatggagtg gagggcttta actgttattt ccctctgcag 1440
agctacggct tccagccaac aaacggcgtg ggctatcagc cctaccgcgt ggtggtgctg 1500
agctttgagc tgctgcacgc acctgcaaca gtgtgcggac caaagaagtc caccaatctg 1560
gtgaagaaca agtgcgtgaa cttcaacttc aacggactga ccggcacagg cgtgctgacc 1620
gagtccaaca agaagttcct gccctttcag cagttcggca gggacatcgc agataccaca 1680
gacgccgtgc gcgaccctca gaccctggag atcctggaca tcacaccatg ctctttcggc 1740
ggcgtgagcg tgatcacacc tggcaccaat acaagcaacc aggtggccgt gctgtatcag 1800
gacgtgaatt gtaccgaggt gcccgtggca atccacgcag atcagctgac ccctacatgg 1860
cgggtgtaca gcaccggctc caacgtgttc cagacaagag ccggatgcct gatcggagca 1920
gagcacgtga acaattccta tgagtgcgac atccctatcg gcgccggcat ctgtgcctct 1980
taccagaccc agacaaactc tccaaggaga gcccgg 2016
<210> 2
<211> 672
<212> PRT
<213> SARS-CoV-2
<400> 2
Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr
1 5 10 15
Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser
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Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn
35 40 45
Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys
50 55 60
Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala
65 70 75 80
Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr
85 90 95
Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn
100 105 110
Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu
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Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe
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Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln
145 150 155 160
Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu
165 170 175
Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser
180 185 190
Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser
195 200 205
Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg
210 215 220
Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp
225 230 235 240
Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr
245 250 255
Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile
260 265 270
Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys
275 280 285
Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn
290 295 300
Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr
305 310 315 320
Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser
325 330 335
Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr
340 345 350
Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly
355 360 365
Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala
370 375 380
Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly
385 390 395 400
Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe
405 410 415
Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val
420 425 430
Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu
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Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser
450 455 460
Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln
465 470 475 480
Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg
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Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys
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Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe
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Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys
530 535 540
Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr
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Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro
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Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser
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Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro
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Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser
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Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala
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Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly
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Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg
660 665 670
<210> 3
<211> 8222
<212> DNA
<213> Artificial Sequence
<220>
<223> AAV-ie Rep-Cap 质粒序列
<400> 3
gcgcgccgat atcgttaacg ccccgcgccg gccgctctag aactagtgga tcccccggaa 60
gatcagaagt tcctattccg aagttcctat tctctagaaa gtataggaac ttctgatctg 120
cgcagccgcc atgccggggt tttacgagat tgtgattaag gtccccagcg accttgacga 180
gcatctgccc ggcatttctg acagctttgt gaactgggtg gccgagaagg aatgggagtt 240
gccgccagat tctgacatgg atctgaatct gattgagcag gcacccctga ccgtggccga 300
gaagctgcag cgcgactttc tgacggaatg gcgccgtgtg agtaaggccc cggaggccct 360
tttctttgtg caatttgaga agggagagag ctacttccac atgcacgtgc tcgtggaaac 420
caccggggtg aaatccatgg ttttgggacg tttcctgagt cagattcgcg aaaaactgat 480
tcagagaatt taccgcggga tcgagccgac tttgccaaac tggttcgcgg tcacaaagac 540
cagaaatggc gccggaggcg ggaacaaggt ggtggatgag tgctacatcc ccaattactt 600
gctccccaaa acccagcctg agctccagtg ggcgtggact aatatggaac agtatttaag 660
cgcctgtttg aatctcacgg agcgtaaacg gttggtggcg cagcatctga cgcacgtgtc 720
gcagacgcag gagcagaaca aagagaatca gaatcccaat tctgatgcgc cggtgatcag 780
atcaaaaact tcagccaggt acatggagct ggtcgggtgg ctcgtggaca aggggattac 840
ctcggagaag cagtggatcc aggaggacca ggcctcatac atctccttca atgcggcctc 900
caactcgcgg tcccaaatca aggctgcctt ggacaatgcg ggaaagatta tgagcctgac 960
taaaaccgcc cccgactacc tggtgggcca gcagcccgtg gaggacattt ccagcaatcg 1020
gatttataaa attttggaac taaacgggta cgatccccaa tatgcggctt ccgtctttct 1080
gggatgggcc acgaaaaagt tcggcaagag gaacaccatc tggctgtttg ggcctgcaac 1140
taccgggaag accaacatcg cggaggccat agcccacact gtgcccttct acgggtgcgt 1200
aaactggacc aatgagaact ttcccttcaa cgactgtgtc gacaagatgg tgatctggtg 1260
ggaggagggg aagatgaccg ccaaggtcgt ggagtcggcc aaagccattc tcggaggaag 1320
caaggtgcgc gtggaccaga aatgcaagtc ctcggcccag atagacccga ctcccgtgat 1380
cgtcacctcc aacaccaaca tgtgcgccgt gattgacggg aactcaacga ccttcgaaca 1440
ccagcagccg ttgcaagacc ggatgttcaa atttgaactc acccgccgtc tggatcatga 1500
ctttgggaag gtcaccaagc aggaagtcaa agactttttc cggtgggcaa aggatcacgt 1560
ggttgaggtg gagcatgaat tctacgtcaa aaagggtgga gccaagaaaa gacccgcccc 1620
cagtgacgca gatataagtg agcccaaacg ggtgcgcgag tcagttgcgc agccatcgac 1680
gtcagacgcg gaagcttcga tcaactacgc agacaggtac caaaacaaat gttctcgtca 1740
cgtgggcatg aatctgatgc tgtttccctg cagacaatgc gagagaatga atcagaattc 1800
aaatatctgc ttcactcacg gacagaaaga ctgtttagag tgctttcccg tgtcagaatc 1860
tcaacccgtt tctgtcgtca aaaaggcgta tcagaaactg tgctacattc atcatatcat 1920
gggaaaggtg ccagacgctt gcactgcctg cgatctggtc aatgtggatt tggatgactg 1980
catctttgaa caataaatga tttaaatcag gtacgcgtct gtgccttcta gttgccagcc 2040
atctgttgtt tgcccctccc ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt 2100
cctttcctaa taaaatgagg aaattgcatc gcattgtctg agtaggtgtc attctattct 2160
ggggggtggg gtggggcagg acagcaaggg ggaggattgg gaagacaata gcaggcatgc 2220
tggggatgcg gtgggctcta tggcaccggt aaaaagatct gttcaaattt gaactgacta 2280
agcggctccc gccagatttt ggcaagatta ctaagcagga agtcaaggac ttttttgctt 2340
gggcaaaggt caatcaggtg ccggtgactc acgagtttaa agttcccagg gaattggcgg 2400
gaactaaagg ggcggagaaa tctctaaaac gcccactggg tgacgtcacc aatactagct 2460
ataaaagtct ggagaagcgg gccaggctct catttgttcc cgagacgcct cgcagttcag 2520
acgtgactgt tgatcccgct cctctgcgac cgctagcttc gatcaactac gcagacaggt 2580
aagtaaacaa atgttctcgt cacgtgggca tgaatctgat gctgtttccc tgcagacaat 2640
gcgagagaat gaatcagaat tcaaatatct gcttcactca cggacagaaa gactgtttag 2700
agtgctttcc cgtgtcagaa tctcaacccg tttctgtcgt caaaaaggcg tatcagaaac 2760
tgtgctacat tcatcatatc atgggaaagg tgccagacgc ttgcactgcc tgcgatctgg 2820
tcaatgtgga tttggatgac tgcatctttg aacaataaat gatttaaatc aggtatggct 2880
gccgatggtt atcttccaga ttggctcgag gacactctct ctgaaggaat aagacagtgg 2940
tggaagctca aacctggccc accaccacca aagcccgcag agcggcataa ggacgacagc 3000
aggggtcttg tgcttcctgg gtacaagtac ctcggaccct tcaacggact cgacaaggga 3060
gagccggtca acgaggcaga cgccgcggcc ctcgagcacg acaaagccta cgaccggcag 3120
ctcgacagcg gagacaaccc gtacctcaag tacaaccacg ccgacgccga gttccaggag 3180
cggctcaaag aagatacgtc ttttgggggc aacctcgggc gagcagtctt ccaggccaaa 3240
aagaggcttc ttgaacctct tggtctggtt gaggaagcgg ctaagacggc tcctggaaag 3300
aagaggcctg tagagcactc tcctgtggag ccagactcct cctcgggaac cggaaaggcg 3360
ggccagcagc ctgcaagaaa aagattgaat tttggtcaga ctggagacgc agactcagtc 3420
ccagaccctc aaccaatcgg agaacctccc gcagccccct caggtgtggg atctcttaca 3480
atggctgcag gcggtggcgc accaatggca gacaataacg agggcgccga cggagtgggt 3540
aattcctcgg gaaattggca ttgcgattcc acatggatgg gcgacagagt catcaccacc 3600
agcacccgaa cctgggccct gcccacctac aacaaccacc tctacaagca aatctccaac 3660
agcacatctg gaggatcttc aaatgacaac gcctacttcg gctacagcac cccctggggg 3720
tattttgact ttaacagatt ccactgccac ttttcaccac gtgactggca gcgactcatc 3780
aacaacaact ggggattccg gcccaagaga ctcagcttca agctcttcaa catccaggtc 3840
aaggaggtca cgcagaatga aggcaccaag accatcgcca ataacctcac cagcaccatc 3900
caggtgttta cggactcgga gtaccagctg ccgtacgttc tcggctctgc ccaccagggc 3960
tgcctgcctc cgttcccggc ggacgtgttc atgattcccc agtacggcta cctaacactc 4020
aacaacggta gtcaggccgt gggacgctcc tccttctact gcctggaata ctttccttcg 4080
cagatgctga gaaccggcaa caacttccag tttacttaca ccttcgagga cgtgcctttc 4140
cacagcagct acgcccacag ccagagcttg gaccggctga tgaatcctct gattgaccag 4200
tacctgtact acttgtctcg gactcaaaca acaggaggca cgacaaatac gcagactctg 4260
ggcttcagcc aaggtgggcc taatacaatg gccaatcagg caaagaactg gctgccagga 4320
ccctgttacc gccagcagcg agtatcaaag acatctgcgg ataacaacaa cagtgaatac 4380
tcgtggactg gagctaccaa gtaccacctc aatggcagag actctctggt gaatccgggc 4440
ccggccatgg caagccacaa ggacgatgaa gaaaagtttt ttcctcagag cggggttctc 4500
atctttggga agcaaggctc agagaaaaca aatgtggaca ttgaaaaggt catgattaca 4560
gacgaagagg aaatcaggac aaccaatccc gtggctacgg agcagtatgg ttctgtatct 4620
accaacctcc agagaggcaa cgatgggact ttggcggtgc cttttaagag acaagcagct 4680
accgcagatg tcaacacaca aggcgttctt ccaggcatgg tctggcagga cagagatgtg 4740
taccttcagg ggcccatctg ggcaaagatt ccacacacgg acggacattt tcacccctct 4800
cccctcatgg gtggattcgg acttaaacac cctccgcctc agatcctgat caagaacacg 4860
cctgtacctg cggatcctcc gaccaccttc aaccagtcaa agctgaactc tttcatcacc 4920
cagtattcta ctggccaagt cagcgtggag atcgagtggg agctgcagaa ggaaaacagc 4980
aagcgctgga accccgagat ccagtacacc tccaactact acaaatctac aagtgtggac 5040
tttgctgtta atacagaagg cgtgtactct gaaccccgcc ccattggcac ccgttacctc 5100
acccgtaatc tgtaattgct tgttaatcaa taaaccgttt aattcgtttc agttgaactt 5160
tggtctctgc gtatttcttt cttatctagt ttccatggct acgtagataa gtagcatggc 5220
gggttaatca ttaactacag cccgggcgtt taaacagcgg gcggaggggt ggagtcgtga 5280
cgtgaattac gtcatagggt tagggaggtc ctgtattaga ggtcacgtga gtgttttgcg 5340
acattttgcg acaccatgtg gtctcgctgg gggggggggc ccgagtgagc acgcagggtc 5400
tccattttga agcgggaggt ttgaacgagc gctggcgcgc tcactggccg tcgttttaca 5460
acgtcgtgac tgggaaaacc ctggcgttac ccaacttaat cgccttgcag cacatccccc 5520
tttcgccagc tggcgtaata gcgaagaggc ccgcaccgat cgcccttccc aacagttgcg 5580
cagcctgaat ggcgaatgga aattgtaagc gttaatattt tgttaaaatt cgcgttaaat 5640
ttttgttaaa tcagctcatt tttttaacca ataggccgaa atcggcaaaa tcccttataa 5700
atcaaaagaa tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact 5760
attaagaacg tggactccaa cgtcaaaggg cgaaaaaccg tctatcaggg cgatggccca 5820
ctacgtgaac catcacccta atcaagtttt ttggggtcga ggtgccgtaa agcactaaat 5880
cggaacccta aagggagccc ccgatttaga gcttgacggg gaaagccggc gaacgtggcg 5940
agaaaggaag ggaagaaagc gaaaggagcg ggcgctaggg cgctggcaag tgtagcggtc 6000
acgctgcgcg taaccaccac acccgccgcg cttaatgcgc cgctacaggg cgcgtcaggt 6060
ggcacttttc ggggaaatgt gcgcggaacc cctatttgtt tatttttcta aatacattca 6120
aatatgtatc cgctcatgag acaataaccc tgataaatgc ttcaataata ttgaaaaagg 6180
aagagtatga gtattcaaca tttccgtgtc gcccttattc ccttttttgc ggcattttgc 6240
cttcctgttt ttgctcaccc agaaacgctg gtgaaagtaa aagatgctga agatcagttg 6300
ggtgcacgag tgggttacat cgaactggat ctcaacagcg gtaagatcct tgagagtttt 6360
cgccccgaag aacgttttcc aatgatgagc acttttaaag ttctgctatg tggcgcggta 6420
ttatcccgta ttgacgccgg gcaagagcaa ctcggtcgcc gcatacacta ttctcagaat 6480
gacttggttg agtactcacc agtcacagaa aagcatctta cggatggcat gacagtaaga 6540
gaattatgca gtgctgccat aaccatgagt gataacactg cggccaactt acttctgaca 6600
acgatcggag gaccgaagga gctaaccgct tttttgcaca acatggggga tcatgtaact 6660
cgccttgatc gttgggaacc ggagctgaat gaagccatac caaacgacga gcgtgacacc 6720
acgatgcctg tagcaatggc aacaacgttg cgcaaactat taactggcga actacttact 6780
ctagcttccc ggcaacaatt aatagactgg atggaggcgg ataaagttgc aggaccactt 6840
ctgcgctcgg cccttccggc tggctggttt attgctgata aatctggagc cggtgagcgt 6900
gggtctcgcg gtatcattgc agcactgggg ccagatggta agccctcccg tatcgtagtt 6960
atctacacga cggggagtca ggcaactatg gatgaacgaa atagacagat cgctgagata 7020
ggtgcctcac tgattaagca ttggtaactg tcagaccaag tttactcata tatactttag 7080
attgatttaa aacttcattt ttaatttaaa aggatctagg tgaagatcct ttttgataat 7140
ctcatgacca aaatccctta acgtgagttt tcgttccact gagcgtcaga ccccgtagaa 7200
aagatcaaag gatcttcttg agatcctttt tttctgcgcg taatctgctg cttgcaaaca 7260
aaaaaaccac cgctaccagc ggtggtttgt ttgccggatc aagagctacc aactcttttt 7320
ccgaaggtaa ctggcttcag cagagcgcag ataccaaata ctgttcttct agtgtagccg 7380
tagttaggcc accacttcaa gaactctgta gcaccgccta catacctcgc tctgctaatc 7440
ctgttaccag tggctgctgc cagtggcgat aagtcgtgtc ttaccgggtt ggactcaaga 7500
cgatagttac cggataaggc gcagcggtcg ggctgaacgg ggggttcgtg cacacagccc 7560
agcttggagc gaacgaccta caccgaactg agatacctac agcgtgagct atgagaaagc 7620
gccacgcttc ccgaagggag aaaggcggac aggtatccgg taagcggcag ggtcggaaca 7680
ggagagcgca cgagggagct tccaggggga aacgcctggt atctttatag tcctgtcggg 7740
tttcgccacc tctgacttga gcgtcgattt ttgtgatgct cgtcaggggg gcggagccta 7800
tggaaaaacg ccagcaacgc ggccttttta cggttcctgg ccttttgctg gccttttgct 7860
cacatgttct ttcctgcgtt atcccctgat tctgtggata accgtattac cgcctttgag 7920
tgagctgata ccgctcgccg cagccgaacg accgagcgca gcgagtcagt gagcgaggaa 7980
gcggaagagc gcccaatacg caaaccgcct ctccccgcgc gttggccgat tcattaatgc 8040
agctggcacg acaggtttcc cgactggaaa gcgggcagtg agcgcaacgc aattaatgtg 8100
agttagctca ctcattaggc accccaggct ttacacttta tgcttccggc tcgtatgttg 8160
tgtggaattg tgagcggata acaatttcac acaggaaaca gctatgacca tgattacgcc 8220
aa 8222
<210> 4
<211> 746
<212> PRT
<213> Artificial Sequence
<220>
<223> AAV-ie 衣壳蛋白 VP1序列
<400> 4
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro
35 40 45
Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro
50 55 60
Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala
85 90 95
Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly
100 105 110
Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro
180 185 190
Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ala Gly Gly Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile
225 230 235 240
Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu
245 250 255
Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn
260 265 270
Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg
275 280 285
Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn
290 295 300
Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile
305 310 315 320
Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn
325 330 335
Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu
340 345 350
Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro
355 360 365
Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn
370 375 380
Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe
385 390 395 400
Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr Thr
405 410 415
Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu
420 425 430
Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser
435 440 445
Arg Thr Gln Thr Thr Gly Gly Thr Thr Asn Thr Gln Thr Leu Gly Phe
450 455 460
Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu
465 470 475 480
Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp
485 490 495
Asn Asn Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu
500 505 510
Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His
515 520 525
Lys Asp Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe
530 535 540
Gly Lys Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met
545 550 555 560
Ile Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu
565 570 575
Gln Tyr Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Asp Gly Thr
580 585 590
Leu Ala Val Pro Phe Lys Arg Gln Ala Ala Thr Ala Asp Val Asn Thr
595 600 605
Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu
610 615 620
Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His
625 630 635 640
Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln
645 650 655
Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe
660 665 670
Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln
675 680 685
Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg
690 695 700
Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser
705 710 715 720
Val Asp Phe Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro
725 730 735
Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
740 745
<210> 5
<211> 3820
<212> DNA
<213> Artificial Sequence
<220>
<223> pAAV-CMV-S1-His
<400> 5
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggccgca cgcgttctcg agcgcgttga cattgattat 180
tgactagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca tatatggagt 240
tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac gacccccgcc 300
cattgacgtc aataatgacg tatgttccca tagtaacgcc aatagggact ttccattgac 360
gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa gtgtatcata 420
tgccaagtac gccccctatt gacgtcaatg acggtaaatg gcccgcctgg cattatgccc 480
agtacatgac cttatgggac tttcctactt ggcagtacat ctacgtatta gtcatcgcta 540
ttaccatggt gatgcggttt tggcagtaca tcaatgggcg tggatagcgg tttgactcac 600
ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgg caccaaaatc 660
aacgggactt tccaaaatgt cgtaacaact ccgccccatt gacgcaaatg ggcggtaggc 720
gtgtacggtg ggaggtctat ataagcagag ctggtttagt gaaccgtcag atccgctaga 780
gatccgaatt agccaccatg tacaggatgc aactcctgtc ttgcattgca ctaagtcttg 840
cacttgtcac gaattcacag tgcgtgaacc tgaccacaag gacccagctg ccccctgcct 900
ataccaattc cttcacacgg ggcgtgtact atcccgacaa ggtgtttaga agctccgtgc 960
tgcactctac acaggatctg tttctgcctt tctttagcaa cgtgacctgg ttccacgcca 1020
tccacgtgag cggcaccaat ggcacaaagc ggttcgacaa tccagtgctg ccctttaacg 1080
atggcgtgta cttcgcctct accgagaaga gcaacatcat cagaggctgg atctttggca 1140
ccacactgga ctccaagaca cagtctctgc tgatcgtgaa caatgccacc aacgtcgtga 1200
tcaaggtgtg cgagttccag ttttgtaatg atcctttcct gggcgtgtac tatcacaaga 1260
acaataagag ctggatggag tccgagtttc gcgtgtattc tagcgccaac aattgcacat 1320
ttgagtacgt gtcccagcca ttcctgatgg acctggaggg caagcagggc aatttcaaga 1380
acctgaggga gttcgtgttt aagaatatcg atggctactt caagatctac tctaagcaca 1440
ccccaatcaa cctggtgcgc gacctgccac agggcttcag cgccctggag ccactggtgg 1500
atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 1560
acctgacacc tggcgactcc tctagcggat ggaccgcagg agctgccgcc tactatgtgg 1620
gctatctgca gccaaggacc ttcctgctga agtacaacga gaatggcacc atcacagacg 1680
cagtggattg cgcactggac cccctgagcg agaccaagtg tacactgaag tcctttaccg 1740
tggagaaggg catctatcag acatccaatt tcagggtgca gcccaccgag tctatcgtgc 1800
gctttcccaa tatcacaaac ctgtgccctt ttggcgaggt gttcaacgca accaggttcg 1860
caagcgtgta cgcatggaat aggaagcgga tcagcaactg cgtggccgac tatagcgtgc 1920
tgtacaactc cgcctctttc agcaccttta agtgctatgg cgtgtccccc acaaagctga 1980
atgacctgtg ctttaccaac gtgtacgccg attctttcgt gatcaggggc gacgaggtgc 2040
gccagatcgc accaggacag acaggcaaga tcgcagacta caattataag ctgcctgacg 2100
atttcaccgg ctgcgtgatc gcctggaaca gcaacaatct ggattccaaa gtgggcggca 2160
actacaatta tctgtaccgg ctgtttagaa agtctaatct gaagccattc gagagggaca 2220
tctctacaga gatctaccag gcaggcagca ccccatgcaa tggagtggag ggctttaact 2280
gttatttccc tctgcagagc tacggcttcc agccaacaaa cggcgtgggc tatcagccct 2340
accgcgtggt ggtgctgagc tttgagctgc tgcacgcacc tgcaacagtg tgcggaccaa 2400
agaagtccac caatctggtg aagaacaagt gcgtgaactt caacttcaac ggactgaccg 2460
gcacaggcgt gctgaccgag tccaacaaga agttcctgcc ctttcagcag ttcggcaggg 2520
acatcgcaga taccacagac gccgtgcgcg accctcagac cctggagatc ctggacatca 2580
caccatgctc tttcggcggc gtgagcgtga tcacacctgg caccaataca agcaaccagg 2640
tggccgtgct gtatcaggac gtgaattgta ccgaggtgcc cgtggcaatc cacgcagatc 2700
agctgacccc tacatggcgg gtgtacagca ccggctccaa cgtgttccag acaagagccg 2760
gatgcctgat cggagcagag cacgtgaaca attcctatga gtgcgacatc cctatcggcg 2820
ccggcatctg tgcctcttac cagacccaga caaactctcc aaggagagcc cggggtggag 2880
gcggatccca ccatcaccat caccattgat atcaagctta tcgataatca acctctggat 2940
tacaaaattt gtgaaagatt gactggtatt cttaactatg ttgctccttt tacgctatgt 3000
ggatacgctg ctttaatgcc tttgtatcat gctattgctt cccgtatggc tttcattttc 3060
tcctccttgt ataaatcctg gttgctgtct ctttatgagg agttgtggcc cgttgtcagg 3120
caacgtggcg tggtgtgcac tgtgtttgct gacgcaaccc ccactggttg gggcattgcc 3180
accacctgtc agctcctttc cgggactttc gctttccccc tccctattgc cacggcggaa 3240
ctcatcgccg cctgccttgc ccgctgctgg acaggggctc ggctgttggg cactgacaat 3300
tccgtggtgt tgtcggggaa atcatcgtcc tttccttggc tgctcgcctg tgttgccacc 3360
tggattctgc gcgggacgtc cttctgctac gtcccttcgg ccctcaatcc agcggacctt 3420
ccttcccgcg gcctgctgcc ggctctgcgg cctcttccgc gacttcgcct tcgccctcag 3480
acgagtcgga tctccctttg ggccgcctcc ccgcagatct aacttgttta ttgcagctta 3540
taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 3600
gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct ggctagacac 3660
gtgcggaccg agcggccgca ggaaccccta gtgatggagt tggccactcc ctctctgcgc 3720
gctcgctcgc tcactgaggc cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg 3780
gcggcctcag tgagcgagcg agcgcgcagc tgcctgcagg 3820
<210> 6
<211> 5027
<212> DNA
<213> Artificial Sequence
<220>
<223> pAAV-CMV-EGFP DNA
<400> 6
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggccgca cgcgttctcg agcgcgttga cattgattat 180
tgactagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca tatatggagt 240
tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac gacccccgcc 300
cattgacgtc aataatgacg tatgttccca tagtaacgcc aatagggact ttccattgac 360
gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa gtgtatcata 420
tgccaagtac gccccctatt gacgtcaatg acggtaaatg gcccgcctgg cattatgccc 480
agtacatgac cttatgggac tttcctactt ggcagtacat ctacgtatta gtcatcgcta 540
ttaccatggt gatgcggttt tggcagtaca tcaatgggcg tggatagcgg tttgactcac 600
ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgg caccaaaatc 660
aacgggactt tccaaaatgt cgtaacaact ccgccccatt gacgcaaatg ggcggtaggc 720
gtgtacggtg ggaggtctat ataagcagag ctggtttagt gaaccgtcag atccgctaga 780
gatccgaatt cgccaccatg gtgagcaagg gcgaggagct gttcaccggg gtggtgccca 840
tcctggtcga gctggacggc gacgtaaacg gccacaagtt cagcgtgtcc ggcgagggcg 900
agggcgatgc cacctacggc aagctgaccc tgaagttcat ctgcaccacc ggcaagctgc 960
ccgtgccctg gcccaccctc gtgaccaccc tgacctacgg cgtgcagtgc ttcagccgct 1020
accccgacca catgaagcag cacgacttct tcaagtccgc catgcccgaa ggctacgtcc 1080
aggagcgcac catcttcttc aaggacgacg gcaactacaa gacccgcgcc gaggtgaagt 1140
tcgagggcga caccctggtg aaccgcatcg agctgaaggg catcgacttc aaggaggacg 1200
gcaacatcct ggggcacaag ctggagtaca actacaacag ccacaacgtc tatatcatgg 1260
ccgacaagca gaagaacggc atcaaggtga acttcaagat ccgccacaac atcgaggacg 1320
gcagcgtgca gctcgccgac cactaccagc agaacacccc catcggcgac ggccccgtgc 1380
tgctgcccga caaccactac ctgagcaccc agtccgccct gagcaaagac cccaacgaga 1440
agcgcgatca catggtcctg ctggagttcg tgaccgccgc cgggatcact ctcggcatgg 1500
acgagctgta caagtaagat atcaagctta tcgataatca acctctggat tacaaaattt 1560
gtgaaagatt gactggtatt cttaactatg ttgctccttt tacgctatgt ggatacgctg 1620
ctttaatgcc tttgtatcat gctattgctt cccgtatggc tttcattttc tcctccttgt 1680
ataaatcctg gttgctgtct ctttatgagg agttgtggcc cgttgtcagg caacgtggcg 1740
tggtgtgcac tgtgtttgct gacgcaaccc ccactggttg gggcattgcc accacctgtc 1800
agctcctttc cgggactttc gctttccccc tccctattgc cacggcggaa ctcatcgccg 1860
cctgccttgc ccgctgctgg acaggggctc ggctgttggg cactgacaat tccgtggtgt 1920
tgtcggggaa atcatcgtcc tttccttggc tgctcgcctg tgttgccacc tggattctgc 1980
gcgggacgtc cttctgctac gtcccttcgg ccctcaatcc agcggacctt ccttcccgcg 2040
gcctgctgcc ggctctgcgg cctcttccgc gacttcgcct tcgccctcag acgagtcgga 2100
tctccctttg ggccgcctcc ccgcagatct aacttgttta ttgcagctta taatggttac 2160
aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact gcattctagt 2220
tgtggtttgt ccaaactcat caatgtatct tatcatgtct ggctagacac gtgcggaccg 2280
agcggccgca ggaaccccta gtgatggagt tggccactcc ctctctgcgc gctcgctcgc 2340
tcactgaggc cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag 2400
tgagcgagcg agcgcgcagc tgcctgcagg ggcgcctgat gcggtatttt ctccttacgc 2460
atctgtgcgg tatttcacac cgcatacgtc aaagcaacca tagtacgcgc cctgtagcgg 2520
cgcattaagc gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc 2580
cctagcgccc gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc 2640
ccgtcaagct ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct 2700
cgaccccaaa aaacttgatt tgggtgatgg ttcacgtagt gggccatcgc cctgatagac 2760
ggtttttcgc cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac 2820
tggaacaaca ctcaacccta tctcgggcta ttcttttgat ttataaggga ttttgccgat 2880
ttcggcctat tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa 2940
aatattaacg tttacaattt tatggtgcac tctcagtaca atctgctctg atgccgcata 3000
gttaagccag ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct 3060
cccggcatcc gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt 3120
ttcaccgtca tcaccgaaac gcgcgagacg aaagggcctc gtgatacgcc tatttttata 3180
ggttaatgtc atgataataa tggtttctta gacgtcaggt ggcacttttc ggggaaatgt 3240
gcgcggaacc cctatttgtt tatttttcta aatacattca aatatgtatc cgctcatgag 3300
acaataaccc tgataaatgc ttcaataata ttgaaaaagg aagagtatga gtattcaaca 3360
tttccgtgtc gcccttattc ccttttttgc ggcattttgc cttcctgttt ttgctcaccc 3420
agaaacgctg gtgaaagtaa aagatgctga agatcagttg ggtgcacgag tgggttacat 3480
cgaactggat ctcaacagcg gtaagatcct tgagagtttt cgccccgaag aacgttttcc 3540
aatgatgagc acttttaaag ttctgctatg tggcgcggta ttatcccgta ttgacgccgg 3600
gcaagagcaa ctcggtcgcc gcatacacta ttctcagaat gacttggttg agtactcacc 3660
agtcacagaa aagcatctta cggatggcat gacagtaaga gaattatgca gtgctgccat 3720
aaccatgagt gataacactg cggccaactt acttctgaca acgatcggag gaccgaagga 3780
gctaaccgct tttttgcaca acatggggga tcatgtaact cgccttgatc gttgggaacc 3840
ggagctgaat gaagccatac caaacgacga gcgtgacacc acgatgcctg tagcaatggc 3900
aacaacgttg cgcaaactat taactggcga actacttact ctagcttccc ggcaacaatt 3960
aatagactgg atggaggcgg ataaagttgc aggaccactt ctgcgctcgg cccttccggc 4020
tggctggttt attgctgata aatctggagc cggtgagcgt gggtctcgcg gtatcattgc 4080
agcactgggg ccagatggta agccctcccg tatcgtagtt atctacacga cggggagtca 4140
ggcaactatg gatgaacgaa atagacagat cgctgagata ggtgcctcac tgattaagca 4200
ttggtaactg tcagaccaag tttactcata tatactttag attgatttaa aacttcattt 4260
ttaatttaaa aggatctagg tgaagatcct ttttgataat ctcatgacca aaatccctta 4320
acgtgagttt tcgttccact gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg 4380
agatcctttt tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac cgctaccagc 4440
ggtggtttgt ttgccggatc aagagctacc aactcttttt ccgaaggtaa ctggcttcag 4500
cagagcgcag ataccaaata ctgtccttct agtgtagccg tagttaggcc accacttcaa 4560
gaactctgta gcaccgccta catacctcgc tctgctaatc ctgttaccag tggctgctgc 4620
cagtggcgat aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac cggataaggc 4680
gcagcggtcg ggctgaacgg ggggttcgtg cacacagccc agcttggagc gaacgaccta 4740
caccgaactg agatacctac agcgtgagct atgagaaagc gccacgcttc ccgaagggag 4800
aaaggcggac aggtatccgg taagcggcag ggtcggaaca ggagagcgca cgagggagct 4860
tccaggggga aacgcctggt atctttatag tcctgtcggg tttcgccacc tctgacttga 4920
gcgtcgattt ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc 4980
ggccttttta cggttcctgg ccttttgctg gccttttgct cacatgt 5027
<210> 7
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> N589和R590之间插入的氨基酸片段
<400> 7
Asp Gly Thr Leu Ala Val Pro Phe Lys
1 5
Claims (9)
1.一种重组病毒载体,其特征在于,其以变异型相关病毒AAV-ie为骨架,并包含编码新冠病毒S1蛋白的核苷酸片段;其中:所述变异型相关病毒AAV-ie的衣壳蛋白相比于野生型AAV-DJ衣壳蛋白VP1,在N589和R590之间插入氨基酸片段,所述氨基酸片段的氨基酸序列如SEQ ID NO: 7所示;所述变异型相关病毒AAV-ie的衣壳蛋白的氨基酸序列如SEQ ID NO: 4所示;所述新冠病毒S1蛋白的氨基酸序列如SEQ ID NO: 2所示;编码所述新冠病毒S1蛋白的核苷酸序列如SEQ ID NO: 1所示。
2.如权利要求1所述的重组病毒载体,其特征在于,其包含如SEQ ID NO: 5所示的序列。
3.一种重组病毒,其包含如权利要求1或2所述的重组病毒载体。
4. 如权利要求3所述的重组病毒,其特征在于,其制备方法包括:将pHelper质粒、AAV-ie Rep-Cap辅助包装质粒以及如权利要求1或2所述的重组病毒载体转染HEK 293T细胞后进行培养。
5.如权利要求4所述的重组病毒,其特征在于,通过磷酸钙进行所述转染。
6. 如权利要求4或5所述的重组病毒,其特征在于,所述AAV-ie Rep-Cap辅助包装质粒含有如SEQ ID NO: 3所示的序列。
7.一种新冠病毒疫苗,其包含如权利要求3~6任一项所述的重组病毒。
8.一种套装药盒,其包含如权利要求1或2所述的重组病毒载体、如权利要求3~6任一项所述的重组病毒或者如权利要求7所述的新冠病毒疫苗。
9.如权利要求1或2所述的重组病毒载体或者如权利要求3~6任一项所述的重组病毒在制备新冠病毒疫苗中的应用。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110437317A (zh) * | 2019-01-30 | 2019-11-12 | 上海科技大学 | 具有变异衣壳蛋白的腺相关病毒及其用途 |
CN111518175A (zh) * | 2020-05-11 | 2020-08-11 | 广州派真生物技术有限公司 | Sars-cov-2抗原多肽及其重组腺相关病毒和在制备疫苗中的应用 |
CN111996216A (zh) * | 2020-09-01 | 2020-11-27 | 中国科学技术大学 | 腺相关病毒介导的新型冠状病毒抗体诱导物及疫苗组合物 |
CN112245578A (zh) * | 2020-10-20 | 2021-01-22 | 王立良 | 一种covid-19病毒预防性疫苗及其制备方法 |
CN112300251A (zh) * | 2020-02-24 | 2021-02-02 | 四川大学 | 抗SARS-CoV-2感染的蛋白及疫苗 |
-
2021
- 2021-05-14 CN CN202110529026.5A patent/CN115340998B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110437317A (zh) * | 2019-01-30 | 2019-11-12 | 上海科技大学 | 具有变异衣壳蛋白的腺相关病毒及其用途 |
CN112300251A (zh) * | 2020-02-24 | 2021-02-02 | 四川大学 | 抗SARS-CoV-2感染的蛋白及疫苗 |
CN111518175A (zh) * | 2020-05-11 | 2020-08-11 | 广州派真生物技术有限公司 | Sars-cov-2抗原多肽及其重组腺相关病毒和在制备疫苗中的应用 |
CN111996216A (zh) * | 2020-09-01 | 2020-11-27 | 中国科学技术大学 | 腺相关病毒介导的新型冠状病毒抗体诱导物及疫苗组合物 |
CN112245578A (zh) * | 2020-10-20 | 2021-01-22 | 王立良 | 一种covid-19病毒预防性疫苗及其制备方法 |
Non-Patent Citations (1)
Title |
---|
Simeng Zhao等.A protective AAV vaccine for SARS-CoV-2.signal transduction and targeted therapy.2022,第1-4页. * |
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