TW202308685A - 冠狀病毒和流感病毒組合物及其使用方法 - Google Patents
冠狀病毒和流感病毒組合物及其使用方法 Download PDFInfo
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Abstract
本文提供了用於誘導針對流感病毒和冠狀病毒兩者的免疫反應的組合物和方法。本文提供了組合物和使用所述組合物的方法,其中所述組合物包含:(a) 處於去污劑-核心奈米顆粒形式的冠狀病毒S(CoV S)醣蛋白,其中所述去污劑是非離子去污劑;(b) 至少三種血凝素(HA)醣蛋白,其中每種HA醣蛋白來自不同的流感毒株;和 (c) 醫藥上可接受的緩衝液。
Description
本公開文本涉及用於誘導針對流感病毒和冠狀病毒兩者的免疫反應的組合物和方法。
流感和冠狀病毒疾病2019(COVID-19)分別是由流感病毒和突發急性呼吸道冠狀病毒2(SARS-CoV-2)引起的威脅生命的疾患。診斷為患有流感的患者的病死率為大約0.1%,並且診斷為患有COVID-19的患者的病死率範圍為0.2%至7.7%。
期望開發預防這些威脅生命的感染性疾病或減輕其嚴重程度的疫苗。然而,由於病原體的逃避機制非常複雜並且難以穩定疫苗,因此人類疫苗的開發仍然具有挑戰性。最佳地,疫苗必須同時誘導阻斷或中和感染原的抗體,並且在各種環境(包括不能製冷的環境)中保持穩定。在單一疫苗組合物中組合來自兩種病原體的兩種抗原特別具有挑戰性,因為抗原可能彼此相互作用,阻礙對任一種病原體的足夠免疫反應。
本公開文本提供了用於誘導針對流感病毒和冠狀病毒兩者的免疫反應的組合物和方法。
本文提供了一種免疫原性組合物,其包含:(a) 處於去污劑-核心奈米顆粒形式的冠狀病毒S(CoV S)醣蛋白,其中所述去污劑是非離子去污劑;(b) 至少三種血凝素(HA)醣蛋白,其中每種HA醣蛋白來自不同的流感毒株;和 (c) 醫藥上可接受的緩衝液。在實施例中,所述至少三種HA醣蛋白處於選自以下的形式:(a) 包含血凝素(HA)的去污劑-核心奈米顆粒;(b) HaSMaN(血凝素皂苷基質奈米顆粒);(c) 滅活的全流感病毒;(d) 從流感病毒提取的血凝素組合物;任選地流感裂解病毒粒子組合物或亞單位流感病毒組合物;以及它們的任何組合。在實施例中,至少一種HA醣蛋白處於包含HA的去污劑-核心奈米顆粒的形式,並且至少一種HA醣蛋白處於HaSMaN的形式。在實施例中,所述去污劑-核心奈米顆粒的血凝素醣蛋白來自乙型流感毒株。在實施例中,所述去污劑-核心奈米顆粒的血凝素醣蛋白來自甲型流感毒株。在實施例中,所述去污劑-核心奈米顆粒是胰蛋白酶抗性奈米顆粒。在實施例中,所述HaSMaN是胰蛋白酶抗性奈米顆粒。在實施例中,每種HA醣蛋白來自不同的流感毒株。在實施例中,所述免疫原性組合物包含多至4種、多至5種、多至6種、多至7種、多至8種、多至9種或多至10種HA醣蛋白。在實施例中,每種HA醣蛋白都處於奈米顆粒的形式。在實施例中,每個奈米顆粒包含來自單一流感毒株的HA醣蛋白。在實施例中,每個奈米顆粒是去污劑-核心奈米顆粒或HaSMaN。在實施例中,所述免疫原性組合物包含佐劑。在實施例中,所述佐劑是皂苷佐劑。在實施例中,所述皂苷佐劑包含至少兩種iscom顆粒,其中:第一iscom顆粒包含皂樹(
Quillaja SaponariaMolina)的級分A,且不包含皂樹的級分C;並且第二iscom顆粒包含皂樹的級分C,且不包含皂樹的級分A。在實施例中,分別地,皂樹的級分A占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計50%-96%,並且皂樹的級分C占剩餘部分。在實施例中,皂樹的級分A和皂樹的級分C分別占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計約85%和按重量計約15%。在實施例中,所述免疫原性組合物包含約50 µg或約75 µg的皂苷佐劑。在實施例中,所述去污劑是PS80。在實施例中,所述流感毒株是選自H1、H2、H3、H4、H5、H6、H7、H8、H9、H10、H11、H12、H13、H14、H15、H16、H17和H18的亞型的毒株。在實施例中,所述醫藥上可接受的緩衝液包含 (i) 約25 mM的磷酸鈉;(ii) 約150 mM的氯化鈉;(iii) 約100 mM的鹽酸精胺酸;(iv) 約5%的海藻糖;其中所述組合物的pH為約7.5。在實施例中,所述CoV S醣蛋白包含 (i) 具有滅活的弗林蛋白酶切割位點的S1亞基,其中所述S1亞基包含N末端結構域(NTD)、受體結合結構域(RBD)、亞結構域1和亞結構域2(SD1/2),其中所述滅活的弗林蛋白酶切割位點具有QQAQ的胺基酸序列(SEQ ID NO: 7);其中所述NTD任選地包含選自以下的一個或多個修飾:(a) 選自胺基酸56、57、131、132、144、145、228、229、230、231、234、235、236、237、238、239、240及其組合的一個或多個胺基酸的缺失;(b) 在胺基酸132後1、2、3或4個胺基酸的插入;以及 (c) 選自胺基酸5、6、7、13、51、53、56、57、62、63、67、82、125、129、131、132、133、139、143、144、145、177、200、201、202、209、229、233、240、245及其組合的一個或多個胺基酸的突變;其中所述RBD任選地包含選自胺基酸333、404、419、426、439、440、464、465、471、477、481、488及其組合的一個或多個胺基酸的突變;其中所述SD1/2結構域任選地包含選自557、600、601、642、664、668及其組合的一個或多個胺基酸的突變;以及 (ii) S2亞基,其中胺基酸973和974是脯胺酸,其中所述S2亞基任選地包含選自以下的一個或多個修飾:(a) 一個或多個胺基酸從676-685、676-702、702-711、775-793、806-815及其組合的缺失;(b) 選自688、703、846、875、937、969、1014、1058、1105和1163及其組合的一個或多個胺基酸的突變;以及 (c) 一個或多個胺基酸從TMCT的缺失;其中所述CoV S醣蛋白的胺基酸相對於具有SEQ ID NO: 2的序列的多肽編號。在實施例中,所述CoV S醣蛋白包含與SEQ ID NO: 86-89、105、106、112-115和164-168中的任一個具有至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性的胺基酸序列或由所述胺基酸序列組成。在實施例中,所述CoV S醣蛋白包含與SEQ ID NO: 87至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同的序列。在實施例中,所述免疫原性組合物包含約1 µg至約50 µg的CoV S醣蛋白和約5 µg至約60 µg的血凝素/毒株。在實施例中,所述免疫原性組合物包含約20 µg至約50 µg的CoV S醣蛋白和約24 µg至約40 µg的血凝素/毒株。在實施例中,所述免疫原性組合物包含約3 µg、約5 µg、約25 µg、約22.5 µg、約7.5 µg或約2.5 µg的冠狀病毒S醣蛋白。在實施例中,所述免疫原性組合物包含約5 µg、約10 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg或約60 µg的血凝素/毒株。
在實施例中,本文提供了一種在受試者中刺激針對SARS-CoV-2、異源SARS-CoV-2毒株、流感病毒或其組合的免疫反應的方法,其包括投予本文所述的任何免疫原性組合物。在實施例中,向所述受試者在第0天投予第一劑量,並且在第56天投予加強劑量。在實施例中,將所述免疫原性組合物肌內投予。在實施例中,投予單劑量的所述免疫原性組合物。在實施例中,所述異源SARS-CoV-2毒株選自Cal.20C SARS-CoV-2毒株、P.1 SARS-CoV-2毒株、B.1.351 SARS-CoV-2毒株、B.1.1.7 SARS-CoV-2毒株、SARS-CoV-2 B.1.617.2毒株、B.1.525毒株、B.1.526毒株、B.1.617.1毒株、C.37毒株、B.1.621毒株或SARS-CoV-2 ο毒株。在實施例中,所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是至少50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%或約100%。在實施例中,所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是約50%至約99%、約50%至約95%、約50%至約90%、約50%至約85%、約50%至約80%、約60%至約99%、約60%至約95%、約60%至約90%、約60%至約85%、約60%至約80%、約40%至約99%、約40%至約95%、約40%至約90%、約40%至約85%、約40%至約80%、約40%至約75%、約40%至約70%、約40%至約65%、約40%至約55%或約40%至約50%。在實施例中,本文提供了一種包含本文所述的任何免疫原性組合物的載藥注射器。
相關申請的交叉引用
本申請要求2021年5月5日提交的美國專利申請號63/184,727;2021年5月26日提交的美國申請號63/193,356;2021年10月14日提交的美國申請號63/255,685;2022年4月19日提交的美國申請號63/332,537的優先權。上述專利文獻中的每一個都通過引用以其整體併入本文。
電子提交的文字檔的說明
將與此一起以電子方式提交的以下文字檔的內容通過引用以其整體併入本文:序列表的電腦可讀格式拷貝(檔案名:NOVV_093_01WO_SeqList_ST25.txt,記錄日期:2022年4月22日,文件大小:976千位元組)。
定義
如本文和所附申請專利範圍所用,單數形式“一個/一種(a)”、“一個/一種(an)”和“所述(the)”包括複數指代物,除非上下文另外明確地規定。因此,例如,提及“一種蛋白質”可以指一種蛋白質或這種蛋白質的混合物,並且提及“所述方法”包括提及本領域技術人員已知的等同步驟和/或方法,等等。
如本文所用,術語“佐劑”是指當與免疫原組合使用時增加或以其他方式改變或修飾針對所述免疫原誘導的免疫反應的化合物。免疫反應的修飾可以包括強化或擴大抗體免疫反應和細胞免疫反應中任一者或兩者的特異性。
如本文所用,當在數值之前時,術語“約”或“大約”指示所述值加或減10%的範圍。例如,“約100”涵蓋90和110。
如本文所用,術語“免疫原”、“抗原”和“表位”是指能夠引發免疫反應的物質,諸如蛋白質(包括醣蛋白)和肽。
如本文所用,“免疫原性組合物”是包含抗原的組合物,其中向受試者投予所述組合物導致在所述受試者中產生針對所述抗原的體液免疫反應和/或細胞免疫反應。
如本文所用,“亞單位”組合物(例如疫苗)包括一種或多種來自病原體的選定抗原,但不是全部抗原。這樣的組合物基本上不含完整的病毒或此類細胞或顆粒的裂解物,並且通常由至少部分純化的(通常基本上純化的)來自所述病原體的免疫原性多肽製備。通常使用杆狀病毒系統,通常以重組方式製備本文公開的亞單位組合物中的抗原。
如本文所用,“基本上”是指這樣分離物質(例如化合物、多核苷酸或多肽),使得所述物質形成包含其的樣品的大多數百分比。例如,在樣品中,基本上純化的組分構成所述樣品的85%,優選85%-90%,更優選至少95%-99.5%,並且最優選至少99%。如果組分基本上被替代,則在樣品中剩餘的量小於或等於約0.5%至約10%,優選小於約0.5%至約1.0%。
如本文所用,術語“治療”(“treat”、“treatment”和“treating”)是指用於獲得有益或期望的結果(例如,臨床結果)的方法。出於本公開文本的目的,有益或期望的結果可以包括抑制或壓制感染或疾病的開始或進展;改善感染或疾病的症狀或減輕其發展;或其組合。
如本文所用,“預防”(“prevention”)與“防預”(“prophylaxis”)可互換使用,並且可以意指完全預防感染或疾病,或預防這種感染或疾病的症狀的發展;延遲感染或疾病或其症狀的發作;或降低隨後發展的感染或疾病或其症狀的嚴重程度。
如本文所用,“有效劑量”或“有效量”是指免疫原的這樣的量,所述量足以誘導減輕病原體感染的至少一種症狀的免疫反應。可以例如通過測量中和分泌抗體和/或血清抗體的量,例如通過噬斑中和、補體結合、酶聯免疫吸附(ELISA)或微量中和測定來確定有效劑量或有效量。
如本文所用,術語“疫苗”是指免疫原性組合物,例如來源於病原體的免疫原,其用於誘導針對病原體的免疫反應。免疫反應可以包括抗體和/或細胞介導的反應的形成。取決於上下文,術語“疫苗”也可以指投予於受試者以產生免疫反應的免疫原懸浮液或溶液。優選地,疫苗誘導有效預防SARS-CoV-2、其SARS-CoV-2變體、流感或其組合感染的免疫反應。
如本文所用,術語“受試者”包括人和其他動物。通常,受試者是人。例如,受試者可以是成人、青少年、兒童(2歲至14歲)、嬰兒(出生至2歲)或新生兒(多至2個月)。在特定方面,受試者多至4個月大或多至6個月大。在多方面中,成人是約65歲或更大或約60歲或更大的年長者。在多方面中,受試者是孕婦或打算懷孕的婦女。在其他方面,受試者不是人;例如非人靈長類動物;例如,狒狒、黑猩猩、大猩猩或獼猴。在某些方面,受試者可以是寵物,諸如狗或貓。
在多方面中,受試者是免疫功能受損的。在實施例中,對免疫功能受損的受試者投予引起免疫抑制的藥物。引起免疫抑制的藥物的非限制性例子包括皮質類固醇(例如,潑尼松)、烷基化劑(例如,環磷醯胺)、抗代謝藥(例如,硫唑嘌呤或6-巰基嘌呤)、移植相關的免疫抑制藥物(例如,環孢菌素、他克莫司、西羅莫司或嗎替麥考酚酯)、米托蒽醌、化療劑、甲胺蝶呤、腫瘤壞死因子(TNF)-阻斷劑(例如,依那西普、阿達木單抗、英夫利昔單抗)。在實施例中,所述免疫功能受損的受試者被病毒(例如,人類免疫缺陷病毒或愛潑斯坦-巴爾病毒)感染。在實施例中,所述病毒是呼吸道病毒,如呼吸道合胞病毒、流感病毒、副流感病毒、腺病毒或小核糖核酸病毒。在實施例中,所述免疫受損的受試者患有獲得性免疫缺陷症候群(AIDS)。在實施例中,所述免疫受損的受試者是人類免疫缺陷病毒(HIV)感染者。在實施例中,所述免疫受損的受試者是由於被設計用於預防炎症或預防移植物排斥的治療方案而免疫受損的。在實施例中,所述免疫受損的受試者是已經接受移植物的受試者。在實施例中,所述免疫受損的受試者已經經歷了放射療法或脾切除術。在實施例中,所述免疫受損的受試者已被診斷為患有癌症、自身免疫病、結核病、物質使用障礙(例如,酒精、阿片類物質或可卡因使用障礙)、中風或腦血管疾病、實體器官或血液幹細胞移植、鐮狀細胞病、地中海貧血、自身免疫性淋巴增殖症候群(ALPS)、自身免疫性多內分泌腺症候群1型(APS-1)、NF-κB相關B細胞增殖和T細胞失能(BENTA)疾病、半胱天冬酶8缺陷狀態(CEDS)、慢性肉芽腫病(CGD)、常見變異型免疫缺陷病(CVID)、先天性中性粒細胞減少症候群、細胞毒性T淋巴細胞相關抗原4(CTLA-4)缺陷、DOCK8缺陷、GATA2缺陷、伴有免疫缺陷的醣基化障礙、高免疫球蛋白E症候群(HIES)、高免疫球蛋白M症候群、糖尿病、1型糖尿病、2型糖尿病、干擾素γ缺陷、白細胞介素12缺陷、白細胞介素23缺陷、白細胞粘附缺陷症、脂多糖反應性米色樣錨蛋白(LRBA)缺陷、PI3激酶疾病、PLCG2相關抗體缺陷和免疫失調(PLAID)、重症聯合免疫缺陷(SCID)、STAT3顯性負性疾病、STAT3功能獲得性疾病、疣、低丙球蛋白血症、感染、和骨髓粒細胞缺乏(WHIM)症候群、Wisckott-Aldrich症候群(WAS)、X連鎖無丙種球蛋白血症(XLA)、X連鎖淋巴組織增殖性疾病(XLP)、尿毒癥、營養不良或XMEN疾病。在實施例中,所述免疫受損的受試者是當前吸菸者或曾經吸菸者。在實施例中,所述免疫受損的受試者患有B細胞缺陷、T細胞缺陷、巨噬細胞缺陷、細胞因子缺陷、吞噬細胞缺陷、吞噬細胞功能異常、補體缺陷或其組合。
在實施例中,所述受試者超重或肥胖。在實施例中,超重受試者具有≥ 25 kg/m
2且< 30 kg/m
2的體重指數(BMI)。在實施例中,肥胖受試者具有≥ 30 kg/m
2的BMI。在實施例中,所述受試者患有精神健康病症。在實施例中,所述精神健康病症是抑鬱症、精神分裂症或焦慮症。
如本文所用,術語“醫藥上可接受的”意指由美國聯邦政府或州政府的監管機構批准或在美國藥典、歐洲藥典或其他公認藥典中列出用於哺乳動物,且更特別地用於人。這些組合物可以用作用於在脊椎動物中誘導保護性免疫反應的疫苗和/或抗原組合物。
如本文所用,術語“約”意指加或減所指示數值的10%。
如本文所用,術語“NVX-CoV2373”是指包含BV2373纖突醣蛋白(SEQ ID NO: 87)以及級分A和級分C iscom基質(例如,MATRIX-M
TM)的疫苗組合物。
如本文所用,“Quad-NIV”、“QuadNIV”或“四價奈米顆粒流感疫苗”或“qNIV”是指含有來自四種流感病毒株的抗原的流感疫苗配製品。
如本文所用,術語“修飾”當提及CoV S多肽時是指CoV S多肽的一個或多個胺基酸的突變、缺失或添加。CoV S多肽內修飾的位置可以通過將多肽的序列與SEQ ID NO: 1(含有信號肽的CoV S多肽)或SEQ ID NO: 2(缺少信號肽的成熟CoV S多肽)比對來確定。
在本文中可與“異源SARS-CoV-2毒株”互換使用的術語SARS-CoV-2的變體是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽相比具有至少約2個、至少約3個、至少約4個、至少約5個、至少約6個、至少約7個、至少約8個、至少約9個、至少約10個、至少約11個、至少約12個、至少約13個、至少約14個、至少約15個、至少約16個、至少約17個、至少約18個、至少約19個、至少約20個、至少約21個、至少約22個、至少約23個、至少約24個、至少約25個、至少約26個、至少約27個、至少約28個、至少約29個、至少約30個、至少約31個、至少約32個、至少約33個、至少約34個、或至少約35個修飾、在約2個與約35個之間的修飾、在約5個與約10個之間的修飾、在約5個與約20個之間的修飾、在約10個與約20個之間的修飾、在約15個與約25個之間的修飾、在約20個與約30個之間的修飾、在約20個與約40個之間的修飾、在約25個與約45個之間的修飾。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約95%、至少約96%、至少約97%、至少約98%、或至少約99%同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約70%與約99.9%之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約70%與約99.5 %之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約90 %與約99.9%之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約90 %與約99.8 %之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約95 %與約99.9%之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約95 %與約99.8 %之間的同一性。在實施例中,所述異源SARS-CoV-2毒株是包含如下CoV S多肽的SARS-CoV-2病毒,所述CoV S多肽與具有SEQ ID NO: 1或SEQ ID NO: 2的胺基酸序列的CoV S多肽具有在約95 %與約99 %之間的同一性。
術語“B.1.1.7 SARS-CoV-2毒株”(也稱為“α”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽包含胺基酸69、70和144的缺失以及N501Y、A570D、D614G、P681H或P681R、T716I、S982A和D1118H的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。B.1.1.7 SARS-CoV-2毒株的CoV S多肽可以任選地含有胺基酸145的缺失,E484K、L432R或S494P的突變,或其組合。
術語“B.1.351 SARS-CoV-2毒株”(也稱為“β”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽包含D80A、K417N、E484K、N501Y、D614G和A701V的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。B.1.617.2 SARS-CoV-2毒株的CoV S多肽可以任選地含有以下突變中的一個或多個:D215G;L242H;R246I;或241-243中1、2或3個胺基酸的缺失,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述β毒株的CoV S多肽包含D80A、D215G、L242H、K417N、E484K、N501Y、D614G和A701V的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述β毒株的CoV S多肽包含突變D80A,D215G,胺基酸241-243中1、2或3個胺基酸的缺失,K417N,E484K,N501Y,D614G,和A701V,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述β毒株包含D80A、L242H、R246I、N501Y、K417N、E484K、D614G和A701V的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“P.1 SARS-CoV-2毒株”(也稱為“γ”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變L18F、T20N、P26S、D138Y、R190S、K417T、E484K、N501Y、D614G、H655Y、T1027I和V1176F,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“Cal.20C SARS-CoV-2毒株”是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變S13I、W152C和L452R,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“B.1.617.2毒株”(也稱為“δ”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、E156G、L452R、T478K、D614G、P681R和D950N的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。B.1.617.2 SARS-CoV-2毒株的CoV S多肽可以任選地含有以下突變中的一個或多個:G142D;W64H;H66W;V70F;T95I;Y145H;D213V;L214R;A222V;W258I或W258L;K417N;N439K;E484K或E484Q;N501Y;和Q613H,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述δ毒株包含如下CoV S多肽,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、G142D、E156G、L452R、T478K、D614G、P681R和D950N的突變。在實施例中,所述δ毒株包含如下CoV S多肽,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、T95I、G142D、Y145H、E156G、A222V、K417N L452R、T478K、D614G、P681R和D950N的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述δ毒株包含如下CoV S多肽,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、G142D、E156G、W258I、K417N、N439K、L452R T478K、E484K、N501Y、D614G、P681R和D950N的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述δ毒株包含如下CoV S多肽,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、W64H、H66W、G142D、E156G、D213V、L214R、W258I、K417N、N439K、L452R、T478K、E484K、N501Y、D614G、P681R和D950N的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述δ毒株包含如下CoV S多肽,所述CoV S多肽包含胺基酸157和158的缺失以及T19R、G142D、E156G、K417N、L452R、T478K、E484Q、D614G、P681R和D950N的突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“B.1.525毒株”(也稱為“η”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變Q52R;A67V;E484K;D614G;Q677H;F888L;以及胺基酸69、70、144、145中的1、2、3或4個的缺失,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“B.1.526毒株”(也稱為“ι”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變L5F;T95I;D253G;E484K;D614G;和A701V,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“B.1.617.1毒株”(也稱為“κ”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變L452R;E484Q;D614G;P681R;和Q1071H,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“C.37毒株”(也稱為“λ”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變G75V;T76I;R246N;L452Q;F490S;D614G;T859N;以及胺基酸247-253中的1、2、3、4、5或6個的缺失,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
術語“B.1.621毒株”(也稱為“µ”毒株)是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽含有突變T95I;Y144S;Y145N;R346K;E484K;N501Y;D614G;P681H;和D950N,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
可與“ο”變體互換使用的術語“B.1.1.529毒株”是指具有如下CoV S多肽的異源SARS-CoV-2毒株,所述CoV S多肽包含突變G142D;G339D;S373P;S375F;K417N;N440K;T478K;E484A或E484K;Q493K或Q493R;Q498R;N501Y;Y505H;D614G;H655Y;N679K;P681H;N764K;D796Y;Q954H;和N969K,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。B.1.1.529 SARS-CoV-2毒株的CoV S多肽可以任選地含有下列突變中的一個或多個:T19I;L24S;A67V;T95I;N211I;L212I或L212V;V213P或V213G;R214E;S371L;T376A;D405N;R408S;G446S;S477N;G496S;T547K;N856K;L981F;G496S;在胺基酸25後胺基酸PPA的插入;胺基酸214或215後胺基酸EPE的插入;或胺基酸25、26、27、69、70、143、144、145、211、212中的一個或多個的缺失;其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。任選地,所述SARS-CoV-2 S ο變體是SARS-CoV-2 S ο BA.1變體。這種毒株在SARS-CoV-2 S多肽中包含下列突變,其中所述多肽相對於SEQ ID NO: 1編號:A67V;胺基酸69-70的缺失;T95I;G142D;胺基酸143-145的缺失;N211I;胺基酸212的缺失;胺基酸214後胺基酸EPE的插入;G339D;S371L;S373P;S375F;K417N;N440K;G446S;S477N;T478K;E484A;Q493R;G496S;Q498R;N501Y;Y505H;T547K;D614G;H655Y;N679K;P681H;N764K;D796Y;N856K;Q954H;N969K;和L981F。任選地,所述SARS-CoV-2 S ο變體是SARS-CoV-2 S ο BA.2變體。這種毒株在SARS-CoV-2 S多肽中包含下列突變,其中所述多肽相對於SEQ ID NO: 1編號:T19I;L24S;胺基酸25-27中的缺失;G142D;V213G;G339D;S371F;S373P;S375F;T376A;D405N;R408S;K417N;N440K;S477N;T478K;E484A;Q493R;Q498R;N501Y;Y505H;D614G;H655Y;N679K;P681H;N764K;D796Y;Q954H;和N969K。
對於SARS-CoV-2或其變體呈“陽性”的受試者具有對於SARS-CoV-2或其變體的陽性PCR或血清學測試。陽性PCR測試檢測來自SARS-CoV-2或其變體的遺傳物質。陽性血清學測試顯示存在針對SARS-CoV-2蛋白(通常是來自SARS-CoV-2或其變體的核衣殼蛋白)的抗體。
術語“無症狀”是指對SARS-CoV-2或其SARS-CoV-2變體呈陽性,但沒有經歷任何COVID-19症狀的受試者。
術語“輕度”當提及COVID-19時是指受試者具有對於SARS-CoV-2或其變體的陽性PCR或血清學測試並且具有以下症狀中的一種或多種:(i) 發燒;(ii) 新發咳嗽;(iii) 或選自以下的兩種另外的COVID-19症狀:新發或惡化的呼吸短促或呼吸困難;疲勞;全身性肌肉或身體疼痛;頭痛;喪失味覺或嗅覺;咽喉痛、充血或流鼻涕;或噁心、嘔吐或腹瀉。
術語“中度”當提及COVID-19時是指受試者具有對於SARS-CoV-2或其變體的陽性PCR或血清學測試以及以下症狀中的一種或多種:(i) ≥ 38.4ºC的高燒持續三天或更多天;(ii) 顯著下呼吸道感染(LRTI)的任何跡象,其中所述跡象選自:(a) 用力或不用力時的呼吸短促;(b) 呼吸急促(靜息時每分鐘呼吸24至29次);(c) 94%至95%的SpO2;(d) 與肺炎或LRTI一致的異常胸部x光照片或電腦斷層攝影(CT);或(e) 肺部聽診時的附加音(例如,劈啪/羅音、喘息音、鼾音、胸膜摩擦音、喘鳴)。
術語“重度”當提及COVID-19時是指受試者具有對於SARS-CoV-2或其變體的陽性PCR或血清學測試以及以下症狀中的一種或多種:(i) 呼吸急促,靜息時每分鐘呼吸≥ 30次;(ii) 靜息心率≥ 125次/分鐘;(iii) SpO2 ≤ 93%或PaO2/FiO2 < 300 mmHg;(iv) 需要高流量氧療或非侵入性通氣、非侵入性正壓通氣(例如,持續氣道正壓(CPAP)或雙水準氣道正壓(BiPAP));(v) 需要機械通氣或體外膜氧合(ECMO);(vi) 一種或多種主要器官系統功能障礙或衰竭,其選自 (a) 急性呼吸衰竭,包括急性呼吸窘迫症候群(ARDS);(b) 急性腎衰竭;(c) 急性肝衰竭;(d) 急性右或左心衰竭;(e) 膿毒性休克或心源性休克(休克定義為收縮壓(SBP)< 90 mmHg或舒張壓(DBP)< 60 mmHg);(f) 急性中風(缺血性或出血性);(g) 急性血栓形成事件,如急性心肌梗塞(AMI)、深靜脈血栓(DVT)或肺栓塞(PE);(h) 需要血管加壓劑、全身性皮質類固醇或血液透析;(vii) 進入重症監護病房;或 (viii) 死亡。
如本文所用,術語“床邊混合物”、“床邊配製品”、“床邊疫苗組合物”、“床邊小瓶”、“床邊小瓶配製品”是指在投予前立即製備的疫苗配製品。此類疫苗配製品含有病毒抗原和佐劑,它們分別儲存在不同的容器中並被投予於受試者(例如,投予兩個連續注射劑,或在投予前將抗原和佐劑合併成一個注射劑)。
如本文所用,術語“共配製品混合物”、“共配製品”、“共配製品疫苗組合物”、“載藥注射器”、“預混合物”是指在投予於受試者之前製備用於短期至長期儲存的疫苗配製品。此類疫苗配製品在同一容器中含有抗原和佐劑的組合,並在投予前製備。在實施例中,所述配製品含有血凝素和佐劑(例如,皂苷佐劑),所述血凝素和所述佐劑形成HaSMaN(血凝素皂苷基質奈米顆粒)。
本文所述的免疫原性組合物或疫苗組合物的術語“功效”是指與未投予免疫原性組合物的組相比,投予免疫原性組合物的組中疾病(例如,COVID-19)的減輕百分比。在實施例中,使用以下等式計算功效(E):E (%) = (1 – RR) × 100,其中RR = 投予所述免疫原性組合物的組與未投予所述免疫原性組合物的組之間的相對發病風險率。在實施例中,本文所述的免疫原性組合物具有針對SARS-CoV-2病毒或異源SARS-CoV-2毒株的功效,所述功效為至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%、至少約99%、在約50%與約99%之間、在約50%與約98%之間、在約60%與約99%之間、在約60%與約98%之間、在約70%與約98%之間、在約70%與約95%之間、在約70%與約99%之間、在約80%與約99%之間、在約80%與約98%之間、在約80%與約95%之間、在約85%與約99%之間、在約85%與約98%之間、在約85%與約95%之間、在約90%與約95%之間、在約90%與98%之間、或在約90%與約99%之間。
如本文所用,術語“裂解病毒粒子”是指具有已用表面活性劑破壞的病毒膜的病毒(例如,流感病毒或SARS-CoV-2病毒)。表面活性劑的例子在本公開文本中通篇描述。裂解病毒粒子不經歷進一步純化,因此它們通常含有多種病毒蛋白。
如本文所用,術語“重組”是指通過引入細胞中的核酸的轉錄和轉譯而在細胞中產生的蛋白質(例如,血凝素)。所述核酸可以經由編碼所述核酸的載體或病毒引入。
如本文所用,術語“全流感病毒”是指包含其包膜、病毒膜、核衣殼和遺傳物質全部的病毒。在實施例中,所述全流感病毒是滅活的。
如本文所用,術語“滅活的病毒”是指與野生型病毒相比,已經經歷處理以基本上降低或消除其毒力的病毒。
針對冠狀病毒和流感病毒的免疫原性組合物
本文提供了免疫原性組合物和疫苗組合物,其含有 (i) 至少三種血凝素(HA)醣蛋白,其中所述三種血凝素(HA)醣蛋白來自不同的流感毒株;(ii) 處於去污劑-核心奈米顆粒形式的CoV S多肽,其中所述去污劑是非離子去污劑,以及 (iii) 醫藥上可接受的緩衝液。在實施例中,所述至少三種HA醣蛋白處於選自以下的形式:(a) 包含血凝素(HA)的去污劑-核心奈米顆粒;(b) HaSMaN(血凝素皂苷基質奈米顆粒);(c) 滅活的全流感病毒;(d) 從流感病毒提取的血凝素組合物;任選地流感裂解病毒粒子組合物或亞單位流感病毒組合物;以及它們的任何組合。在實施例中,本文提供了使用上述免疫原性組合物和疫苗組合物以刺激針對冠狀病毒、流感病毒或其組合的免疫反應的方法。
本文還提供了製造上述奈米顆粒和免疫原性組合物的方法。有利地,所述方法提供了基本上沒有被其他蛋白質污染的奈米顆粒,所述其他蛋白質是諸如與蛋白質在昆蟲細胞中的重組表現相關的蛋白質。在實施例中,表現發生在杆狀病毒/Sf9系統中。
(i) 非天然存在的 CoV S 多肽或奈米顆粒
本公開文本的免疫原性組合物含有非天然存在的CoV S多肽或包含其的奈米顆粒。CoV S多肽可以源自冠狀病毒,包括但不限於SARS-CoV-2,例如源自SARS-CoV-2、源自MERS CoV和源自SARS CoV。
在實施例中,SARS-CoV-2的變體是SARS-CoV-2 VUI 202012/01, B.1.1.7(也稱為“501Y.V1”和“α”)、B.1.351(也稱為“501Y.V2”和“β”)、B.1.617.2(也稱為“δ”)、Cal.20C(也稱為“ε”)或P.1(也稱為“γ”)。SARS-CoV-2的變體由世界衛生組織(WHO)標記(例如,α、β、γ、δ等)、其系統發育歸類命名全球暴發(PANGO)譜系、其GISAID進化枝或其Nextstrain進化枝命名。
下表提供了變體SARS-CoV-2毒株的列表:
WHO標記 | Pango 譜系* | GISAID進化枝 | Nextstrain進化枝 | 與SEQ ID NO: 1相比的修飾 | 與SEQ ID NO: 1相比的任選修飾 |
α | B.1.1.7 | GRY | 20I (V1) | 胺基酸69和70的缺失;胺基酸144的缺失;N501Y;A570D;D614G;P681H或P681R;T716I;S982A;和D1118H | 胺基酸145的缺失;E484K;L432R;S494P |
β | B.1.351 | GH/501Y.V2 | 20H (V2) | D80A; K417N; E484K; N501Y; D614G; A701V; | D215G; L242H; R246I; 241-243中的1、2或3個胺基酸的缺失 |
γ | P.1 | GR/501Y.V3 | 20J (V3) | L18F;T20N;P26S;D138Y;R190S;K417T;E484K;N501Y;D614G;H655Y;T1027I;和V1176F | |
δ | B.1.617.2 | G/478K.V1 | 21A、21I、21J | T19R;E156G;胺基酸157和158的缺失;L452R;T478K;D614G;P681R;D950N | G142D;W64H;H66W;V70F;T95I; Y145H; D213V; L214R; A222V; W258I或W258L;K417N;N439K;E484K或E484Q;N501Y;Q613H |
η | B.1.525 | Q52R;A67V;胺基酸69-70的缺失;胺基酸144-145的缺失;E484K;D614G;Q677H;F888L | |||
ι | B.1.526 | L5F;T95I;D253G;E484K;D614G;A701V | |||
κ | B.1.617.1 | L452R;E484Q;D614G;P681R;Q1071H | |||
λ | C.37 | G75V;T76I;R246N;247-253中的1、2、3、4、5或6個胺基酸的缺失;L452Q;F490S;D614G;T859N | |||
µ | B.1.621 | T95I;Y144S;Y145N;R346K;E484K;N501Y;D614G;P681H;D950N |
在實施例中,所述SARS-CoV-2病毒具有如下CoV S多肽,所述CoV S多肽具有SEQ ID NO: 1的胺基酸序列,並且SARS-CoV-2的變體包含如下CoV S多肽,所述CoV S多肽與SEQ ID NO: 1相比具有至少約1個、至少約2個、至少約3個、至少約4個、至少約5個、至少約6個、至少約7個、至少約8個、至少約9個、至少約10個、至少約11個、至少約12個、至少約13個、至少約14個、至少約15個、至少約16個、至少約17個、至少約18個、至少約19個、至少約20個、至少約21個、至少約22個、至少約23個、至少約24個、至少約25個、至少約26個、至少約27個、至少約28個、至少約29個、至少約30個、至少約31個、至少約32個、至少約33個、至少約34個、至少約35個、至少約36個、至少約37個、至少約38個、至少約39個、至少約40個、至少約41個、至少約42個、至少約43個、至少約44個、至少約45個、至少約46個、至少約47個、至少約48個、至少約49個、至少約50個、至少約51個、至少約52個、至少約53個、至少約54個、至少約55個、至少約56個、至少約57個、至少約58個、至少約59個、至少約60個、至少約61個、至少約62個、至少約63個、至少約64個、至少約65個、至少約66個、至少約67個、至少約68個、至少約69個、或至少約70個修飾。
與SARS-CoV S蛋白相比,SARS-CoV-2 S蛋白在S1/S2切割位點中具有四個胺基酸插入,從而產生多鹼基RRAR弗林蛋白酶樣切割基序。SARS-CoV-2 S蛋白被合成為無活性前體(S0),其在弗林蛋白酶切割位點處被蛋白水解切割成S1亞基和S2亞基,這些亞基保持非共價連接以形成融合前三聚體。SARS-CoV-2 S蛋白的S2結構域包含融合肽(FP)、兩個七肽重複區(HR1和HR2)、跨膜(TM)結構域和胞質尾(CT)。SARS-CoV-2 S蛋白的S1結構域折疊成四個不同的結構域:N末端結構域(NTD)和含有受體結合結構域(RBD)的C末端結構域以及兩個亞結構域SD1和SD2。融合前SARS-CoV-2 S蛋白三聚體在S蛋白受體結合和切割後經歷從融合前到融合後構象的結構重排。
在實施例中,由於轉譯後醣基化,所述CoV S多肽是醣蛋白。所述醣蛋白包含信號肽、S1亞基、S2亞基、NTD、RBD、兩個亞結構域(SD1和SD2,在
圖 6A- 圖 6B中標記為SD1/2並且在本文中稱為“SD1/2”)、完整或修飾的融合肽、HR1結構域、HR2結構域、TM和CD中的一種或多種。在實施例中,每個結構域的胺基酸在
圖 6A(根據SEQ ID NO: 1顯示)和
圖 6B(根據SEQ ID NO: 2顯示)中給出。在實施例中,每個結構域可以與如在SEQ ID NO: 1或SEQ ID NO: 2中的每個結構域的序列具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性。每個結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2中所示的那些相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約20個、或多至約30個胺基酸的缺失、插入或突變。每個結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2中所示的那些相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。應注意,
圖 2和
圖 3展示了成熟肽中不存在的13個胺基酸的N末端信號肽。所述CoV S多肽可以用於刺激針對天然CoV纖突(S)多肽的免疫反應。
在實施例中,修飾天然CoV纖突(S)多肽(SEQ ID NO: 2),從而產生非天然存在的CoV纖突(S)多肽
在實施例中,修飾天然CoV纖突(S)多肽(SEQ ID NO: 2),從而產生非天然存在的CoV纖突(S)多肽(
圖 1)。在實施例中,所述CoV纖突(S)醣蛋白包含S1亞基和S2亞基,其中所述S1亞基包含NTD、RBD、SD1/2和無活性的弗林蛋白酶切割位點(胺基酸669-672),並且其中所述S2亞基包含胺基酸973和974的突變;
其中所述NTD(胺基酸1-318)任選地包含選自以下的一個或多個修飾:
(a) 選自胺基酸56、57、131、132、144、145、228、229、230、231、234、235、236、237、238、239、240及其組合的一個或多個胺基酸的缺失;
(b) 在胺基酸132後1、2、3或4個胺基酸的插入;以及
(c) 選自胺基酸5、6、7、13、39、51、53、54、56、57、62、63、67、82、125、129、131、132、133、139、143、144、145、177、200、201、202、209、229、233、240、245及其組合的一個或多個胺基酸的突變;
其中所述RBD任選地包含選自胺基酸333、404、419、426、439、440、464、465、471、477、481、488及其組合的一個或多個胺基酸的突變;
其中所述SD1/2結構域任選地包含選自557、600、601、642、664、668及其組合的一個或多個胺基酸的突變;以及
其中所述S2亞基任選地包含選自以下的一個或多個修飾:
(a) 一個或多個胺基酸從676-685、676-702、702-711、775-793、806-815及其組合的缺失;
(b) 選自胺基酸688、703、846、875、937、969、973、974、1014、1058、1105和1163及其組合的一個或多個胺基酸的突變;以及
(c) 一個或多個胺基酸從跨膜和胞質結構域(TMCT)(胺基酸1201-1260)中的缺失,
其中所述CoV S醣蛋白的胺基酸相對於SEQ ID NO: 2編號。
在實施例中,本文所述的CoV S多肽以融合前構象存在。在實施例中,本文所述的CoV S多肽包含柔性HR2結構域。除非另外提及,否則結構域的柔性通過透射電子顯微術(TEM)和2D類別取平均值來確定。電子密度的降低對應於柔性結構域。
對 S1 亞基的修飾
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 121的胺基酸序列的S1亞基的一個或多個修飾。
所述S1亞基的胺基酸序列(SEQ ID NO: 121)示於下文。
QCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRAR
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的S1亞基具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的S1亞基。所述S1亞基可以具有與SEQ ID NO: 1或SEQ ID NO: 2的S1亞基的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個、或多至約30個胺基酸的缺失、插入或突變。所述S1亞基可以具有與SEQ ID NO: 1或SEQ ID NO: 2的S1亞基相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述S1亞基可以含有表1A中所示的修飾的任何組合。
表1A
對 S1 亞基 -NTD 的修飾
對 S1(SEQ ID NO: 121) 的修飾 *SEQ ID NO: 1的胺基酸14-685和SEQ ID NO: 2的胺基酸1-672 | |||
在 SEQ ID NO: 1 內的位置 | 在 SEQ ID NO: 2 內的位置 | 在 SEQ ID NO: 121 內的位置 | 潛在修飾 |
14-305 | 1-292 | 1-292 | 多至約1、2、3、4、5、10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290或292個胺基酸的缺失 |
18 | 5 | 5 | 突變成苯丙胺酸 突變成酪胺酸 突變成色胺酸 |
19 | 6 | 6 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 |
20 | 7 | 7 | 突變成天門冬醯胺酸 突變成麩醯胺酸 突變成異白胺酸 突變成擷胺酸 |
26 | 13 | 13 | 突變成絲胺酸 突變成蘇胺酸 |
52 | 39 | 39 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 |
64 | 51 | 51 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
66 | 53 | 53 | 突變成色胺酸 突變成酪胺酸 突變成苯丙胺酸 |
67 | 54 | 54 | 突變成擷胺酸 突變成異白胺酸 突變成白胺酸 |
69 | 56 | 56 | 胺基酸的缺失 |
70 | 57 | 57 | 胺基酸的缺失 突變成苯丙胺酸 突變成酪胺酸 突變成色胺酸 |
75 | 62 | 62 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 |
76 | 63 | 63 | 突變成異白胺酸 突變成擷胺酸 突變成白胺酸 |
80 | 67 | 67 | 突變成丙胺酸 突變成甘胺酸 |
95 | 82 | 82 | 突變成β支鏈胺基酸 突變成異白胺酸 突變成擷胺酸 |
138 | 125 | 125 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
142 | 129 | 129 | 突變成天門冬胺酸 突變成麩胺酸 |
144 | 131 | 131 | 胺基酸的缺失 突變成絲胺酸 |
145 | 132 | 132 | 胺基酸的缺失 突變成組胺酸 突變成天門冬醯胺酸 突變成麩醯胺酸 在胺基酸132(例如,天門冬醯胺酸)後1、2、3或4個胺基酸的插入 |
146 | 133 | 133 | 突變成芳香族胺基酸 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
152 | 139 | 139 | 突變成半胱胺酸 突變成甲硫胺酸 突變成絲胺酸 突變成蘇胺酸 |
156 | 143 | 143 | 突變成甘胺酸 突變成丙胺酸 |
157 | 144 | 144 | 胺基酸的缺失 |
158 | 145 | 145 | 胺基酸的缺失 |
190 | 177 | 177 | 突變成絲胺酸 突變成蘇胺酸 突變成半胱胺酸 |
213 | 200 | 200 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 突變成β支鏈胺基酸 |
214 | 201 | 201 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 |
215 | 202 | 202 | 突變成甘胺酸 突變成丙胺酸 |
222 | 209 | 209 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 |
241-244 | 228-231 | 228-231 | 1、2、3或4個胺基酸的缺失 |
242 | 229 | 229 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
246 | 233 | 233 | 突變成β支鏈胺基酸 突變成異白胺酸 突變成擷胺酸 突變成蘇胺酸 突變成天門冬醯胺酸 |
247 | 234 | 234 | 胺基酸的缺失 |
248 | 235 | 235 | 胺基酸的缺失 |
249 | 236 | 236 | 胺基酸的缺失 |
250 | 237 | 237 | 胺基酸的缺失 |
251 | 238 | 238 | 胺基酸的缺失 |
252 | 239 | 239 | 胺基酸的缺失 |
253 | 240 | 240 | 突變成甘胺酸 胺基酸的缺失 |
258 | 245 | 245 | 突變成異白胺酸 突變成擷胺酸 突變成白胺酸 突變成β支鏈胺基酸 |
346 | 333 | 333 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
417 | 404 | 404 | 突變成天門冬醯胺酸 突變成蘇胺酸 突變成異白胺酸 突變成擷胺酸 突變成絲胺酸 突變成麩醯胺酸 突變成β支鏈胺基酸 |
432 | 419 | 419 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
439 | 426 | 426 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
452 | 439 | 439 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 突變成麩醯胺酸 突變成天門冬醯胺酸 |
453 | 440 | 440 | 突變成苯丙胺酸 突變成色胺酸 |
477 | 464 | 464 | 突變成天門冬醯胺酸 突變成麩醯胺酸 |
478 | 465 | 465 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
484 | 471 | 471 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 突變成麩醯胺酸 突變成天門冬醯胺酸 |
490 | 477 | 477 | 突變成絲胺酸 突變成蘇胺酸 |
494 | 481 | 481 | 突變成脯胺酸 |
501 | 488 | 488 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
570 | 557 | 557 | 突變成天門冬胺酸 突變成麩胺酸 |
613 | 600 | 600 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
614 | 601 | 601 | 突變成甘胺酸 突變成丙胺酸 |
655 | 642 | 642 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
677 | 664 | 664 | 突變成組胺酸 |
681 | 668 | 668 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
682-685 | 669-672 | 669-672 | 無活性的弗林蛋白酶切割位點(參見表1E) |
在實施例中,所述CoV S多肽含有對NTD的一個或多個修飾。在實施例中,所述NTD具有SEQ ID NO: 118的胺基酸序列,其對應於SEQ ID NO: 1的胺基酸14-305或SEQ ID NO: 2的胺基酸1-292。
NTD的胺基酸序列(SEQ ID NO: 118)示於下文。
QCVN
LT
TRTQLP
PAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAI
HVSGTNGTKRF
DNPVLPFNDGVYFAS
TEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCN
DPFLGV
YYHKNNKS
WMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNL
REFVFKNIDGYFKIYSKHTPINLVR
DLPQGFSALEPLVDLPIGINITRFQTL
LALH
RSYLTPG
DS
SSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKS
SEQ ID NO: 118的加底線的區域表示NTD內的可以被修飾的胺基酸。
在實施例中,所述NTD具有SEQ ID NO: 45的胺基酸序列,其對應於SEQ ID NO: 1的胺基酸14至331或SEQ ID NO: 2的胺基酸1-318。NTD的胺基酸序列(SEQ ID NO: 45)示於下文。
QCVN
LT
TRTQLP
PAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAI
HVSGTNGTKRF
DNPVLPFNDGVYFAS
TEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCN
DPFLGV
YYHKNNKS
WMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNL
REFVFKNIDGYFKIYSKHTPINLVR
DLPQGFS
ALEPLVDLPIGINITRFQTL
LALH
RSYLTPG
DS
SSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPN
在實施例中,所述NTD和RBD重疊多至約1個胺基酸、多至約5個胺基酸、多至約10個胺基酸、或多至約20個胺基酸。
在實施例中,如本文所提供的NTD可以在C末端延伸多至5個胺基酸、多至10個胺基酸、多至15個胺基酸、多至20個胺基酸、多至25個胺基酸、或多至30個胺基酸。
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的NTD具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的NTD。所述NTD可以具有與SEQ ID NO: 1或SEQ ID NO: 2的NTD的胺基酸序列相比多至約1個胺基酸、多至約2個胺基酸、多至約3個胺基酸、多至約4個胺基酸、多至約5個胺基酸、多至約10個胺基酸、多至約15個胺基酸、多至約20個胺基酸、多至約25個胺基酸、或多至約30個胺基酸的缺失、插入或突變。所述NTD可以具有與SEQ ID NO: 1或SEQ ID NO: 2的NTD相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述CoV S多肽含有一個或多個胺基酸從N末端結構域(NTD)(對應於SEQ ID NO: 2的胺基酸1-292)中的缺失。在實施例中,所述CoV S多肽含有NTD的多至約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290或292個胺基酸的缺失。
在實施例中,所述CoV S多肽含有一個或多個胺基酸從NTD(對應於SEQ ID NO: 2的胺基酸1-318)中的缺失。在實施例中,所述CoV S多肽含有SEQ ID NO: 2的NTD的胺基酸1-318的缺失。在實施例中,NTD的缺失增強了CoV纖突(S)多肽的蛋白質表現。在實施例中,具有NTD缺失的CoV S多肽具有由SEQ ID NO: 46、48、49、51、52和54表示的胺基酸序列。在實施例中,具有NTD缺失的CoV S多肽由選自SEQ ID NO: 47、SEQ ID NO: 50和SEQ ID NO: 53的分離的核酸序列編碼。
在實施例中,所述NTD可以含有表1B中所示的修飾的任何組合。所述修飾相對於供參考的成熟S多肽序列SEQ ID NO: 2示出。
表1B
對 S1 亞基 -RBD 的修飾
對 NTD(SEQ ID NO: 118) 的修飾* SEQ ID NO: 1的胺基酸14-305和SEQ ID NO: 2的胺基酸1-292 | |||
在 SEQ ID NO: 1 內的位置 | SEQ ID NO: 2 殘基 | SEQ ID NO: 121 或 SEQ ID NO: 45 殘基 | 修飾 |
18 | 5 | 5 | 突變成苯丙胺酸 突變成酪胺酸 突變成色胺酸 |
19 | 6 | 6 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 |
20 | 7 | 7 | 突變成天門冬醯胺酸 突變成麩醯胺酸 突變成異白胺酸 突變成擷胺酸 |
26 | 13 | 13 | 突變成絲胺酸 突變成蘇胺酸 |
64 | 51 | 51 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
66 | 53 | 53 | 突變成色胺酸 突變成酪胺酸 突變成苯丙胺酸 |
69 | 56 | 56 | 胺基酸的缺失 |
70 | 57 | 57 | 胺基酸的缺失 突變成苯丙胺酸 突變成酪胺酸 突變成色胺酸 |
75 | 62 | 62 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 |
76 | 63 | 63 | 突變成異白胺酸 突變成擷胺酸 突變成白胺酸 |
80 | 67 | 67 | 突變成丙胺酸 突變成甘胺酸 |
95 | 82 | 82 | 突變成β支鏈胺基酸 突變成異白胺酸 突變成擷胺酸 |
138 | 125 | 125 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
142 | 129 | 129 | 突變成天門冬胺酸 突變成麩胺酸 |
144 | 131 | 131 | 胺基酸的缺失 突變成絲胺酸 |
145 | 132 | 132 | 胺基酸的缺失 突變成組胺酸 突變成天門冬醯胺酸 突變成麩醯胺酸 在此位置後1、2、3或4個胺基酸的插入 |
146 | 133 | 133 | 突變成芳香族胺基酸 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
152 | 139 | 139 | 突變成半胱胺酸 突變成甲硫胺酸 突變成絲胺酸 突變成蘇胺酸 突變成精胺酸 |
156 | 143 | 143 | 突變成甘胺酸 突變成丙胺酸 |
157 | 144 | 144 | 胺基酸的缺失 |
158 | 145 | 145 | 胺基酸的缺失 |
190 | 177 | 177 | 突變成絲胺酸 突變成蘇胺酸 突變成半胱胺酸 |
213 | 200 | 200 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 突變成β支鏈胺基酸 |
214 | 201 | 201 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 |
215 | 202 | 202 | 突變成甘胺酸 突變成丙胺酸 |
222 | 209 | 209 | 突變成擷胺酸 突變成白胺酸 突變成異白胺酸 |
242 | 229 | 229 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
241-244 | 228-231 | 228-231 | 1、2、3或4個胺基酸的缺失 |
246 | 233 | 233 | 突變成β支鏈胺基酸 突變成異白胺酸 突變成擷胺酸 突變成蘇胺酸 突變成天門冬醯胺酸 |
247 | 234 | 234 | 胺基酸的缺失 |
248 | 235 | 235 | 胺基酸的缺失 |
249 | 236 | 236 | 胺基酸的缺失 |
250 | 237 | 237 | 胺基酸的缺失 |
251 | 238 | 238 | 胺基酸的缺失 |
252 | 239 | 239 | 胺基酸的缺失 |
253 | 240 | 240 | 突變成甘胺酸 胺基酸的缺失 |
258 | 245 | 245 | 突變成異白胺酸 突變成擷胺酸 突變成白胺酸 突變成β支鏈胺基酸 |
在實施例中,所述CoV S多肽含有對RBD的一個或多個修飾。
在實施例中,所述RBD具有SEQ ID NO: 126的胺基酸序列,其對應於SEQ ID NO: 1的胺基酸331-527或SEQ ID NO: 2的胺基酸318-514。
所述RBD的胺基酸序列(SEQ ID NO: 126)示於下文:
NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTG
KIADYNYKLPDDFTGCVIAWNS
NNLDSKVGGNYNY
LYRLFRKSNLKPFERDISTEIYQAG
STPCNGV
EGFNCYFPLQSYGFQPT
NGVGYQPYRVVVLSFELLHAPATVCGP
SEQ ID NO: 126的加底線的區域表示RBD亞基內的可以被修飾的胺基酸。
在實施例中,所述RBD具有SEQ ID NO: 116的胺基酸序列,其對應於SEQ ID NO: 1的胺基酸335-530或SEQ ID NO: 2的胺基酸322-517。
所述RBD的胺基酸序列(SEQ ID NO: 116)示於下文。
LCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS
在實施例中,如本文所提供的RBD可以在N末端或C末端延伸多至1個胺基酸、多至5個胺基酸、多至10個胺基酸、多至15個胺基酸、多至20個胺基酸、多至25個胺基酸或多至30個胺基酸。
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的RBD具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的RBD。所述RBD可以具有與SEQ ID NO: 1或SEQ ID NO: 2的RBD的胺基酸序列相比多至約1個胺基酸、多至約2個胺基酸、多至約3個胺基酸、多至約4個胺基酸、多至約5個胺基酸、多至約10個胺基酸、多至約15個胺基酸、多至約20個胺基酸、多至約25個胺基酸、或多至約30個胺基酸的缺失、插入或突變。所述RBD可以具有與SEQ ID NO: 1或SEQ ID NO: 2的RBD相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述CoV S多肽在RBD中具有至少一個、至少二個、至少三個、至少四個、至少5個、至少6個、至少7個、至少8個、至少9個、至少10個、至少11個、至少12個、至少13個、至少14個、至少15個、至少16個、至少17個、至少18個、至少19個或至少20個突變。在實施例中,所述RBD可以含有如表1C中所示的修飾的任何組合。
表1C
對 SD1/2 的修飾
對 RBD(SEQ ID NO: 126) 的修飾* SEQ ID NO: 1的胺基酸331-527和SEQ ID NO: 2的胺基酸318-514 | |||
在 SEQ ID NO: 1 內的位置 | 在 SEQ ID NO: 2 內的位置 | 在 SEQ ID NO: 126 內的位置 | 潛在修飾 |
346 | 333 | 16 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
417 | 404 | 87 | 突變成天門冬醯胺酸 突變成蘇胺酸 突變成異白胺酸 突變成擷胺酸 突變成絲胺酸 突變成麩醯胺酸 突變成β支鏈胺基酸 |
432 | 419 | 102 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
439 | 426 | 109 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
452 | 439 | 122 | 突變成精胺酸 突變成離胺酸 突變成組胺酸 突變成麩醯胺酸 突變成天門冬醯胺酸 |
453 | 440 | 123 | 突變成苯丙胺酸 突變成色胺酸 |
477 | 464 | 147 | 突變成天門冬醯胺酸 突變成麩醯胺酸 |
478 | 465 | 148 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 |
484 | 471 | 154 | 突變成離胺酸 突變成精胺酸 突變成組胺酸 突變成麩醯胺酸 突變成天門冬醯胺酸 |
490 | 477 | 160 | 突變成絲胺酸 突變成蘇胺酸 |
494 | 481 | 164 | 突變成脯胺酸 |
501 | 488 | 171 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 122的胺基酸序列的SD1/2的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸542-681或SEQ ID NO: 2的胺基酸529-668。
所述SD1/2的胺基酸序列(SEQ ID NO: 122)示於下文。
NFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSP
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的SD1/2具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的SD1/2。所述SD1/2可以具有與SEQ ID NO: 1或SEQ ID NO: 2的SD1/2的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個或多至約30個胺基酸的缺失、插入或突變。所述SD1/2可以具有與SEQ ID NO: 1或SEQ ID NO: 2的SD1/2相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述CoV S多肽在SD1/2中具有至少一個、至少二個、至少三個、至少四個、至少5個、至少6個、至少7個、至少8個、至少9個、至少10個、至少11個、至少12個、至少13個、至少14個、至少15個、至少16個、至少17個、至少18個、至少19個或至少20個突變。在實施例中,所述SD1/2可以含有如表1D中所示的修飾的任何組合。
表1D
對弗林蛋白酶切割位點的修飾
對 SD1/2(SEQ ID NO: 122) 的修飾 *SEQ ID NO: 1的胺基酸542-681或SEQ ID NO: 2的胺基酸529-668 | |||
在 SEQ ID NO: 1 內的位置 | 在 SEQ ID NO: 2 內的位置 | 在 SEQ ID NO: 122 內的位置 | 潛在修飾 |
570 | 557 | 29 | 突變成天門冬胺酸 突變成麩胺酸 |
613 | 600 | 600 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
614 | 601 | 73 | 突變成甘胺酸 突變成丙胺酸 |
655 | 642 | 114 | 突變成酪胺酸 突變成苯丙胺酸 突變成色胺酸 |
677 | 664 | 664 | 突變成組胺酸 |
681 | 668 | 140 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 |
在實施例中,所述CoV S多肽含有通過一個或多個突變滅活的弗林蛋白酶位點(RRAR),其對應於SEQ ID NO: 1的胺基酸682-685或SEQ ID NO: 2的胺基酸669-672。弗林蛋白酶切割位點的滅活防止弗林蛋白酶切割CoV S多肽。在實施例中,本文所述的含有滅活的弗林蛋白酶切割位點的CoV S多肽被表現為單鏈。
在實施例中,構成天然弗林蛋白酶切割位點的胺基酸中一個或多個被突變為任何天然胺基酸。在實施例中,所述胺基酸是L-胺基酸。胺基酸的非限制性例子包括丙胺酸、精胺酸、甘胺酸、天門冬醯胺酸、天門冬胺酸、半胱胺酸、麩醯胺酸、麩胺酸、絲胺酸、蘇胺酸、組胺酸、離胺酸、甲硫胺酸、脯胺酸、擷胺酸、異白胺酸、白胺酸、酪胺酸、色胺酸和苯丙胺酸。
在實施例中,構成天然弗林蛋白酶切割位點的胺基酸中的一個或多個被突變為麩醯胺酸。在實施例中,1、2、3或4個胺基酸可以被突變為麩醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的一個被突變為麩醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的兩個被突變為麩醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的三個被突變為麩醯胺酸。
在實施例中,構成天然弗林蛋白酶切割位點的胺基酸中的一個或多個被突變為丙胺酸。在實施例中,1、2、3或4個胺基酸可以被突變為丙胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的一個被突變為丙胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的兩個被突變為丙胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的三個被突變為丙胺酸。
在實施例中,構成天然弗林蛋白酶切割位點的胺基酸中的一個或多個被突變為甘胺酸。在實施例中,1、2、3或4個胺基酸可以被突變為甘胺酸。在實施例中,天然弗林蛋白酶切割位點的精胺酸中的一個被突變為甘胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的兩個被突變為甘胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的三個被突變為甘胺酸。
在實施例中,構成天然弗林蛋白酶切割位點的胺基酸中的一個或多個被突變為天門冬醯胺酸。例如,1、2、3或4個胺基酸可以被突變為天門冬醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的一個被突變為天門冬醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的兩個被突變為天門冬醯胺酸。在實施例中,構成天然弗林蛋白酶切割位點的精胺酸中的三個被突變為天門冬醯胺酸。
包含在所述CoV S多肽內的滅活的弗林蛋白酶位點的胺基酸序列的非限制性例子見於表1E中。
表1E
弗林蛋白酶切割位點的胺基酸序列 | 有活性或無活性的弗林蛋白酶切割位點 |
RRAR (SEQ ID NO: 6) | 有活性 |
QQAQ (SEQ ID NO: 7) | 無活性 |
QRAR (SEQ ID NO: 8) | 無活性 |
RQAR (SEQ ID NO: 9) | 無活性 |
RRAQ (SEQ ID NO: 10) | 無活性 |
QQAR (SEQ ID NO: 11) | 無活性 |
RQAQ (SEQ ID NO: 12) | 無活性 |
QRAQ (SEQ ID NO: 13) | 無活性 |
NNAN (SEQ ID NO: 14) | 無活性 |
NRAR (SEQ ID NO: 15) | 無活性 |
RNAR (SEQ ID NO: 16) | 無活性 |
RRAN (SEQ ID NO: 17) | 無活性 |
NNAR (SEQ ID NO: 18) | 無活性 |
RNAN (SEQ ID NO: 19) | 無活性 |
NRAN (SEQ ID NO: 20) | 無活性 |
AAAA (SEQ ID NO: 21) | 無活性 |
ARAR (SEQ ID NO: 22) | 無活性 |
RAAR (SEQ ID NO: 23) | 無活性 |
RRAA (SEQ ID NO: 24) | 無活性 |
AAAR (SEQ ID NO: 25) | 無活性 |
RAAA (SEQ ID NO: 26) | 無活性 |
ARAA (SEQ ID NO: 27) | 無活性 |
GGAG (SEQ ID NO: 28) | 無活性 |
GRAR (SEQ ID NO: 29) | 無活性 |
RGAR (SEQ ID NO: 30) | 無活性 |
RRAG (SEQ ID NO: 31) | 無活性 |
GGAR (SEQ ID NO: 32) | 無活性 |
RGAG (SEQ ID NO: 33) | 無活性 |
GRAG (SEQ ID NO: 34) | 無活性 |
GSAS (SEQ ID NO: 97) | 無活性 |
GSGA (SEQ ID NO: 111) | 無活性 |
在實施例中,代替有活性的弗林蛋白酶切割位點(SEQ ID NO: 6),本文所述的CoV S多肽含有滅活的弗林蛋白酶切割位點。在實施例中,滅活的弗林蛋白酶切割位點的胺基酸序列由SEQ ID NO: 7-34或SEQ ID NO: 97中的任一個表示。在實施例中,滅活的弗林蛋白酶切割位點的胺基酸序列為QQAQ(SEQ ID NO: 7)。在實施例中,滅活的弗林蛋白酶切割位點的胺基酸序列為GSAS(SEQ ID NO: 97)。在實施例中,滅活的弗林蛋白酶切割位點的胺基酸序列為GSGA(SEQ ID NO: 111)。在實施例中,滅活的弗林蛋白酶切割位點的胺基酸序列為GG、GGG(SEQ ID NO: 127)、GGGG(SEQ ID NO: 128)或GGGGG(SEQ ID NO: 129)。
對 S2 亞基的修飾
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 120的胺基酸序列的S2亞基的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸686-1273或SEQ ID NO: 2的胺基酸673-1260。
所述S2亞基的胺基酸序列(SEQ ID NO: 120)示於下文。
SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的S2亞基具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的S2亞基。所述S2亞基可以具有與SEQ ID NO: 1或SEQ ID NO: 2的S2亞基的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個、或多至約30個胺基酸的缺失、插入或突變。所述S2亞基可以具有與SEQ ID NO: 1或SEQ ID NO: 2的S2亞基相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述S2亞基可以含有如表1F中所示的修飾的任何組合。
表1F
對 S2(SEQ ID NO: 120) 的修飾 *SEQ ID NO: 1的胺基酸686-1273和SEQ ID NO: 2的胺基酸673-1260 | |||
在 SEQ ID NO: 1 內的位置 | 在 SEQ ID NO: 2 內的位置 | 在 SEQ ID NO: 120 內的位置 | 可能的修飾 |
689-698 | 676-685 | 4-13 | 多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約6個、多至約7個、多至約8個、多至約9個或多至約10個胺基酸的缺失 |
701 | 688 | 16 | 突變成β支鏈胺基酸 突變成擷胺酸 突變成異白胺酸 突變成蘇胺酸 |
715-724 | 702-711 | 30-39 | 多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約6個、多至約7個、多至約8個、多至約9個或多至約10個胺基酸的缺失 |
716 | 703 | 31 | 突變成β支鏈胺基酸 突變成擷胺酸 突變成異白胺酸 |
788-806 | 775-793 | 103-121 | 多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約6個、多至約7個、多至約8個、多至約9個、多至約10個、多至約11個、多至約12個、多至約13個、多至約14個、多至約15個、多至約16個、多至約17個、多至約18個或多至約19個胺基酸的缺失 |
819-828 | 806-815 | 134-143 | 多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約6個、多至約7個、多至約8個、多至約9個或多至約10個胺基酸的缺失 |
859 | 846 | 174 | 突變成天門冬醯胺酸 突變成麩醯胺酸 |
888 | 875 | 203 | 突變成白胺酸 突變成異白胺酸 突變成擷胺酸 |
950 | 937 | 265 | 突變成天門冬醯胺酸 突變成麩醯胺酸 |
982 | 969 | 297 | 突變成丙胺酸 突變成甘胺酸 突變成蘇胺酸 |
986 | 973 | 301 | 突變成脯胺酸 突變成甘胺酸 |
987 | 974 | 302 | 突變成脯胺酸 突變成甘胺酸 |
1027 | 1014 | 342 | 突變成異白胺酸 突變成擷胺酸 突變成絲胺酸 |
1071 | 1058 | 386 | 突變成組胺酸 突變成精胺酸 突變成離胺酸 |
1118 | 1105 | 433 | 突變成組胺酸 突變成離胺酸 突變成精胺酸 突變成天門冬醯胺酸 突變成麩醯胺酸 |
1176 | 1163 | 491 | 突變成苯丙胺酸 突變成酪胺酸 突變成色胺酸 |
1214-1237 | 1201-1224 | 1-24 | 跨膜結構域(TM)的一個或多個胺基酸的缺失 |
1238-1273 | 1225-1260 | 1-36 | 胞質結構域(CT)的一個或多個胺基酸的缺失 |
在實施例中,所述CoV S多肽含有缺失,其對應于天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸676-685內的一個或多個缺失。在實施例中,天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸676-685中的1、2、3、4、5、6、7、8、9或10個胺基酸被缺失。在實施例中,胺基酸676-685內的胺基酸的缺失是連續的,例如胺基酸676和677被缺失或者胺基酸680和681被缺失。在實施例中,胺基酸676-685內的胺基酸的缺失是非連續的,例如胺基酸676和680被缺失或者胺基酸677和682被缺失。在實施例中,含有對應於胺基酸676-685內的一個或多個缺失的缺失的CoV S多肽具有選自SEQ ID NO: 62和SEQ ID NO: 63的胺基酸序列。
在實施例中,所述CoV S多肽含有缺失,其對應于天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸702-711內的一個或多個缺失。在實施例中,天然SARS-CoV-2纖突(S)多肽(SEQ ID NO: 2)的胺基酸702-711中的1、2、3、4、5、6、7、8、9或10個胺基酸被缺失。在實施例中,胺基酸702-711內的胺基酸的一個或多個缺失是連續的,例如胺基酸702和703被缺失或者胺基酸708和709被缺失。在實施例中,胺基酸702-711內的胺基酸的缺失是非連續的,例如胺基酸702和704被缺失或者胺基酸707和710被缺失。在實施例中,含有對應於胺基酸702-711內的一個或多個缺失的缺失的CoV S多肽具有選自SEQ ID NO: 64和SEQ ID NO: 65的胺基酸序列。
在實施例中,所述CoV S多肽含有缺失,其對應于天然CoV S多肽(SEQ ID NO: 2)的胺基酸775-793內的一個或多個缺失。在實施例中,天然SARS-CoV-2纖突(S)多肽(SEQ ID NO: 2)的胺基酸775-793中的多至約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18或19個胺基酸被缺失。在實施例中,胺基酸775-793內的胺基酸的一個或多個缺失是連續的,例如胺基酸776和777被缺失或者胺基酸780和781被缺失。在實施例中,胺基酸775-793內的胺基酸的缺失是非連續的,例如胺基酸775和790被缺失或者胺基酸777和781被缺失。
在實施例中,所述CoV S多肽含有融合肽(SEQ ID NO: 104)的缺失,所述融合肽對應於SEQ ID NO: 2的胺基酸806-815。在實施例中,CoV纖突(S)多肽(SEQ ID NO: 2)的融合肽的1、2、3、4、5、6、7、8、9或10個胺基酸被缺失。在實施例中,融合肽內的胺基酸的缺失是連續的,例如胺基酸806和807被缺失或者胺基酸809和810被缺失。在實施例中,融合肽內的胺基酸的缺失是非連續的,例如胺基酸806和808被缺失或者胺基酸810和813被缺失。在實施例中,含有對應于融合肽的一個或多個胺基酸的缺失的CoV S多肽具有選自SEQ ID NO: 66、77和105-108的胺基酸序列。
在實施例中,所述CoV S多肽在天然CoV纖突(S)多肽(SEQ ID NO: 2)的Lys-973處含有突變。在實施例中,Lys-973被突變為任何天然胺基酸。在實施例中,Lys-973被突變為脯胺酸。在實施例中,Lys-973被突變為甘胺酸。在實施例中,在胺基酸973處含有突變的CoV S多肽選自SEQ ID NO: 84-89、105-106和109-110。
在實施例中,所述CoV S多肽在天然CoV纖突(S)多肽(SEQ ID NO: 2)的Val-974處含有突變。在實施例中,Val-974被突變為任何天然胺基酸。在實施例中,Val-974被突變為脯胺酸。在實施例中,Val-974被突變為甘胺酸。在實施例中,在胺基酸974處含有突變的CoV S多肽選自SEQ ID NO: 84-89、105-106和109-110。
在實施例中,所述CoV S多肽在天然CoV纖突(S)多肽(SEQ ID NO: 2)的Lys-973和Val-974處含有突變。在實施例中,Lys-973和Val-974被突變為任何天然胺基酸。在實施例中,Lys-973和Val-974被突變為脯胺酸。在實施例中,在胺基酸973和974處含有突變的CoV S多肽選自SEQ ID NO: 84-89、105-106和109-110。
對 S2 亞基 -HR1 結構域的修飾
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 119的胺基酸序列的HR1結構域的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸912-984或SEQ ID NO: 2的胺基酸889-971。
所述HR1結構域的胺基酸序列(SEQ ID NO: 119)示於下文。
MAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRL
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的HR1結構域具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的HR1結構域。所述HR1結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的HR1結構域的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個或多至約30個胺基酸的缺失、插入或突變。所述HR1結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的HR1結構域相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,所述HR1結構域可以含有如表1G中所示的修飾的任何組合。
表1G
對 S2 亞基 -HR2 結構域的修飾
對 HR1(SEQ ID NO: 119) 的修飾 *SEQ ID NO: 1的胺基酸912-984和SEQ ID NO: 2的胺基酸889-971) | |||
在 SEQ ID NO: 1 內的位置 | 在 SEQ ID NO: 2 內的位置 | 在 SEQ ID NO: 119 內的位置 | 可能的修飾 |
982 | 969 | 81 | 突變成丙胺酸 突變成甘胺酸 突變成蘇胺酸 |
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 125的胺基酸序列的HR2結構域的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸1163-1213或SEQ ID NO: 2的胺基酸1150-1200。
所述HR2結構域的胺基酸序列(SEQ ID NO: 125)示於下文。
DVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWP
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的HR2結構域具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的HR2結構域。所述HR2結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的HR2結構域的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個或多至約30個胺基酸的缺失、插入或突變。所述HR2結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的HR2結構域相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
對 TM 結構域的修飾
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 123的胺基酸序列的TM結構域的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸1214-1237或SEQ ID NO: 2的胺基酸1201-1224。
所述TM結構域的胺基酸序列(SEQ ID NO: 123)示於下文。
WYIWLGFIAGLIAIVMVTIMLCCM
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的TM結構域具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的TM結構域。所述TM結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的TM結構域的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個或多至約30個胺基酸的缺失、插入或突變。所述TM結構域可以具有與SEQ ID NO: 1或SEQ ID NO: 2的TM結構域相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,本文所述的CoV S多肽缺少整個TM結構域。在實施例中,所述CoV S多肽包含TM結構域。
對 CT 的修飾
在實施例中,所述CoV S多肽含有對具有SEQ ID NO: 124的胺基酸序列的CT的一個或多個修飾,所述胺基酸序列對應於SEQ ID NO: 1的胺基酸1238-1273或SEQ ID NO: 2的胺基酸1225-1260。
所述CT的胺基酸序列(SEQ ID NO: 124)示於下文:
TSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
在實施例中,本文所述的CoV S多肽包含與SEQ ID NO: 1或SEQ ID NO: 2的CT具有至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%同一性的CT。所述CT可以具有與SEQ ID NO: 1或SEQ ID NO: 2的CT的胺基酸序列相比多至約1個胺基酸、多至約2個胺基酸、多至約3個胺基酸、多至約4個胺基酸、多至約5個胺基酸、多至約10個胺基酸、多至約15個胺基酸、多至約20個胺基酸、多至約25個胺基酸、或多至約30個胺基酸的缺失、插入或突變。所述CT可以具有與SEQ ID NO: 1或SEQ ID NO: 2的CT相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、或在約25個與30個之間的胺基酸的缺失、插入或突變。
在實施例中,本文所述的CoV S多肽缺少CT。在實施例中,所述CoV S多肽包含CT。
在實施例中,所述CoV S多肽包含TM和CT。在實施例中,所述CoV纖突(S)多肽含有一個或多個胺基酸從跨膜和胞質尾(TMCT)(對應於胺基酸1201-1260)中的缺失。所述TMCT的胺基酸序列由SEQ ID NO: 39表示。在實施例中,具有TMCT的一個或多個殘基的缺失的CoV S多肽具有增強的蛋白質表現。在實施例中,具有來自TMCT的一個或多個缺失的CoV纖突(S)多肽具有選自SEQ ID NO: 40、41、42、52、54、59、61、88和89的胺基酸序列。在實施例中,具有來自TM-CD的一個或多個缺失的CoV S多肽由選自SEQ ID NO: 39、43、53和60的分離的核酸序列編碼。
示例性非天然存在的 CoV S 多肽或奈米顆粒
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56和57的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸131和132的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56和131的缺失。在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸57和131的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56、57和131的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56和132的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸57和132的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56、57和132的缺失。
在實施例中,所述CoV S多肽含有天然CoV纖突(S)多肽(SEQ ID NO: 2)的胺基酸56、57、131和132的缺失。
在實施例中,所述CoV S多肽含有使CoV S多肽的融合前構象穩定的突變。在實施例中,所述CoV S多肽含有使融合前構象穩定的脯胺酸或甘胺酸取代。這種策略已經用於開發融合前穩定的MERS-CoV S蛋白,如以下文獻中所述,所述文獻各自通過引用以其整體併入本文:Proc Natl Acad Sci USA. 2017年8月29日;114(35):E7348-E7357;Sci Rep. 2018年10月24日;8(1):15701;美國公開號2020/0061185;以及PCT申請號PCT/US2017/058370。
在實施例中,所述CoV S多肽含有在Lys-973和Val-974處的突變以及滅活的弗林蛋白酶切割位點。在實施例中,所述CoV S多肽含有Lys-973和Val-974至脯胺酸的突變、具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。含有在Lys-973和Val-974處的突變以及滅活的弗林蛋白酶切割位點的示例性CoV S多肽描繪在
圖 3中。在實施例中,含有Lys-973和Val-974至脯胺酸的突變以及滅活的弗林蛋白酶切割位點的CoV S多肽具有SEQ ID NO: 86或87的胺基酸序列和SEQ ID NO: 96的核酸序列。
在實施例中,所述CoV S多肽含有在Lys-973和Val-974處的突變、滅活的弗林蛋白酶切割位點、以及融合肽的一個或多個胺基酸的缺失。在實施例中,所述CoV S多肽含有Lys-973和Val-974至脯胺酸的突變、具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點、以及融合肽的一個或多個胺基酸的缺失。在實施例中,含有Lys-973和Val-974至脯胺酸的突變、滅活的弗林蛋白酶切割位點、以及融合肽的一個或多個胺基酸的缺失的CoV S多肽具有SEQ ID NO: 105或106的胺基酸序列。在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Leu-5至苯丙胺酸的突變、Thr-7至天門冬醯胺酸的突變、Pro-13至絲胺酸的突變、Asp-125至酪胺酸的突變、Arg-177至絲胺酸的突變、Lys-404至蘇胺酸的突變、Glu-471至離胺酸的突變、Asn-488至酪胺酸的突變、His-642至酪胺酸的突變、Thr-1014至異白胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Trp-139至半胱胺酸的突變、Leu-439至精胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 1),所述CoV S多肽含有Trp-152至半胱胺酸的突變、Leu-452至精胺酸的突變、Ser-13至異白胺酸的突變、Lys-986和Val-987至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Lys-404至蘇胺酸或天門冬醯胺酸的突變、Glu-471至離胺酸的突變、Asn-488至酪胺酸的突變、Leu-5至苯丙胺酸的突變、Asp-67至丙胺酸的突變、Asp-202至甘胺酸的突變、胺基酸229-231中的一個或多個的缺失、Arg-233至異白胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Asn-488至酪胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,具有Asn-488至酪胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 112的胺基酸序列。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Asp-601至甘胺酸的突變、Asn-488至酪胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,具有Asn-488至酪胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 113的胺基酸序列。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有胺基酸56、57和131的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)、GSAS(SEQ ID NO: 96)或GG的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,具有胺基酸56、57和131的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 114的胺基酸序列。在實施例中,具有胺基酸56、57和131的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)或GG的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 136的胺基酸序列。在實施例中,具有胺基酸56、57和131的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 137或SEQ ID NO: 138的胺基酸序列。在一些實施例中,具有SEQ ID NO: 114或SEQ ID NO: 136的胺基酸序列的CoV S多肽由具有SEQ ID NO: 135的核酸序列的核酸編碼。在一些實施例中,具有SEQ ID NO: 137或SEQ ID NO: 138的胺基酸序列的CoV S多肽由具有SEQ ID NO: 139的序列的核酸編碼。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有胺基酸56、57和132的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,具有胺基酸56、57和132的缺失、Asn-488至酪胺酸的突變、Ala-557至天門冬胺酸的突變、Asp-601至甘胺酸的突變、Pro-668至組胺酸的突變、Thr-703至異白胺酸的突變、Ser-969至丙胺酸的突變、Asp-1105至組胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 114的胺基酸序列。
在實施例中,相對于天然CoV纖突(S)多肽(SEQ ID NO: 2),所述CoV S多肽含有Asn-488至酪胺酸的突變、Asp-67至丙胺酸的突變、Leu-229至組胺酸的突變、Asp-202至甘胺酸的突變、Lys-404至天門冬醯胺酸的突變、Glu-471至離胺酸的突變、Ala-688至擷胺酸的突變、Asp-601至甘胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點。在實施例中,具有Asn-488至酪胺酸的突變、Asp-67至丙胺酸的突變、Leu-229至組胺酸的突變、Asp-202至甘胺酸的突變、Lys-404至天門冬醯胺酸的突變、Glu-471至離胺酸的突變、Ala-688至擷胺酸的突變、Asp-601至甘胺酸的突變、Lys-973和Val-974至脯胺酸的突變以及具有QQAQ(SEQ ID NO: 7)或GSAS(SEQ ID NO: 96)的胺基酸序列的滅活的弗林蛋白酶切割位點的CoV S多肽包含SEQ ID NO: 115的胺基酸序列。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、胺基酸56的缺失、胺基酸57的缺失、胺基酸131的缺失、N488Y、A557D、D601G、P668H、T703I、S969A和D1105H,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述滅活的弗林蛋白酶切割位點具有QQAQ(SEQ ID NO: 7)的胺基酸序列。在實施例中,所述滅活的弗林蛋白酶切割位點具有GG的胺基酸序列。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、D67A、D202G、L229H、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述滅活的弗林蛋白酶切割位點具有QQAQ(SEQ ID NO: 7)的胺基酸序列。在實施例中,所述滅活的弗林蛋白酶切割位點具有GG的胺基酸序列。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、具有QQAQ(SEQ ID NO: 7)的胺基酸序列的滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、L5F、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述具有一個或多個修飾的CoV S多肽包含SEQ ID NO: 144的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、具有QQAQ(SEQ ID NO: 7)的胺基酸序列的滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、L5F、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述具有SEQ ID NO: 144的胺基酸序列的CoV S多肽由具有SEQ ID NO: 145的序列的核酸編碼。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、L5F、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述具有一個或多個修飾的CoV S多肽包含SEQ ID NO: 144的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、L5F、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述具有SEQ ID NO: 144的胺基酸序列的CoV S多肽由具有SEQ ID NO: 145的序列的核酸編碼。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、L5F、T7N、P13S、D125Y、R177S、K404T、E471K、N488Y、D601G、H642Y、T1014I和V1163F,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽具有SEQ ID NO: 151的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點、L5F、T7N、P13S、D125Y、R177S、K404T、E471K、N488Y、D601G、H642Y、T1014I和V1163F,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述具有SEQ ID NO: 151的胺基酸序列的CoV S多肽由具有SEQ ID NO: 150的序列的核酸編碼。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、胺基酸229-231的缺失、L5F、D67A、D202G、L229H、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、K404N、E471K、N488Y、L5F、D67A、D202G、L229H、D601G、A688V和胺基酸229-231的缺失,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述滅活的弗林蛋白酶切割位點具有QQAQ(SEQ ID NO: 7)的胺基酸序列。在實施例中,所述滅活的弗林蛋白酶切割位點具有GG的胺基酸序列
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、K404N、E471K和N488K,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、K404N、E471K和N488Y。在實施例中,所述CoV S多肽是具有一個或多個修飾的CoV S多肽的RBD,所述一個或多個修飾選自K973P、V974P、滅活的弗林蛋白酶切割位點、K404N、E471K和N488K,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述CoV S多肽是具有一個或多個修飾的CoV S多肽的RBD,所述一個或多個修飾選自K973P、V974P、滅活的弗林蛋白酶切割位點、K404N、E471K和N488Y,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點、D601G、E404N、E471K和N488Y。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點和D601G突變,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有修飾的CoV S多肽具有SEQ ID NO: 133的胺基酸序列,所述修飾選自:K973P、V974P、具有GG的胺基酸序列的滅活的弗林蛋白酶切割位點和D601G突變。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7)或GG)、K404N、E471K、N488K、D67A、D202G、L229H、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽具有SEQ ID NO: 132或SEQ ID NO: 141的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7)或GG)、K404N、E471K、N488K、D67A、D202G、L229H、D601G和A688V。在實施例中,所述具有SEQ ID NO: 132的胺基酸序列的CoV S多肽由具有SEQ ID NO: 131的核酸序列的核酸編碼。在實施例中,所述具有SEQ ID NO: 132的胺基酸序列的CoV S多肽由具有SEQ ID NO: 142的核酸序列的核酸編碼。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、W139C和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述包含K973P、V974P、滅活的弗林蛋白酶切割位點、W139C和L439R修飾的CoV S多肽表現為含有具有SEQ ID NO: 117或SEQ ID NO: 5的胺基酸序列的信號肽。在實施例中,所述CoV S多肽包含選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、D601G、W139C和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述CoV S多肽包含K973P、V974P、滅活的弗林蛋白酶切割位點、D601G、W139C和L439R修飾,並且表現為含有具有SEQ ID NO: 117或SEQ ID NO: 5的胺基酸序列的信號肽。
在實施例中,所述CoV S多肽包含選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點、D601G、L5F、D67A、D202G、胺基酸229-231的缺失、R233I、K404N、E471K、N488Y和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、W139C、S481P、D601G和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、W139C、D601G和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、W139C、S481P和D601G,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽具有SEQ ID NO: 153的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、W139C、S481P、D601G和L439R。在實施例中,所述具有SEQ ID NO: 153的胺基酸序列的CoV S多肽包含具有SEQ ID NO: 117的胺基酸序列的信號肽。在實施例中,所述具有SEQ ID NO: 153的胺基酸序列的CoV S多肽包含具有SEQ ID NO: 5的胺基酸序列的信號肽。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、E471K、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽具有SEQ ID NO: 156的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、E471K、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽包含具有SEQ ID NO: 154或SEQ ID NO: 5的胺基酸序列的信號肽,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、E471K、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、S464N、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽具有SEQ ID NO: 158的胺基酸序列,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、S464N、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述含有一個或多個修飾的CoV S多肽包含SEQ ID NO: 154的信號肽,所述一個或多個修飾選自:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、T82I、D240G、S464N、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、胺基酸56的缺失、胺基酸57的缺失、胺基酸131的缺失、N488Y突變、A557D突變、D601G突變、P668H突變、T703I突變、S969A突變和D1105H突變,其中所述CoV S多肽相對於具有SEQ ID NO: 2的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、胺基酸56的缺失、胺基酸57的缺失、胺基酸132的缺失、N488Y突變、A557D突變、D601G突變、P668H突變、T703I突變、S969A突變和D1105H突變,其中所述CoV S多肽相對於具有SEQ ID NO: 2的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、D67A突變、L229H突變、R233I突變、A688V突變、N488Y突變、K404N突變、E471K突變和D601G突變,其中所述CoV S多肽相對於具有SEQ ID NO: 2的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K973P、V974P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、L5F突變、T7N突變、P13S突變、D125Y突變、R177S突變、K404T突變、E471K突變、N488Y突變、D601G突變、H642Y突變、T1014I突變和T1163F突變,其中所述CoV S多肽相對於具有SEQ ID NO: 2的胺基酸序列的野生型SARS-CoV-2 S多肽編號。
在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K986P、V987P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、S13I突變、W152C突變和L452R突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列的野生型SARS-CoV-2 S多肽編號。在實施例中,所述CoV S多肽含有選自以下的一個或多個修飾:K986P、V987P、滅活的弗林蛋白酶切割位點(任選地其中所述滅活的弗林蛋白酶切割位點是QQAQ(SEQ ID NO: 7))、S13I突變、W152C突變和L452R突變,其中所述CoV S多肽相對於具有SEQ ID NO: 1的胺基酸序列、缺乏N末端信號肽的野生型SARS-CoV-2 S多肽編號。
在實施例中,所述CoV纖突(S)多肽包含多肽連接子。在實施例中,所述多肽連接子含有甘胺酸和絲胺酸。在實施例中,所述連接子具有約50%、約55%、約60%、約65%、約70%、約75%、約80%、約85%、約90%、約95%或約100%的甘胺酸。
在實施例中,所述多肽連接子具有重複序列(SGGG)
n(SEQ ID NO: 91),其中n是1至50的整數(例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49或50)。在實施例中,所述多肽連接子具有對應於SEQ ID NO: 90的胺基酸序列。
在實施例中,所述多肽連接子具有重複序列(GGGGS)
n(SEQ ID NO: 93),其中n是1至50的整數(例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49或50)。
在實施例中,所述多肽連接子具有重複序列(GGGS)
n(SEQ ID NO: 92),其中n是1至50的整數(例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49或50)。
在多方面中,所述多肽連接子是聚(Gly)n連接子,其中n是1、2、3、4、5、6、7、8、9、10、15、16、17、18、19或20。在其他實施例中,所述連接子選自:二肽、三肽和四肽。在實施例中,所述連接子是選自丙胺酸-絲胺酸(AS)、白胺酸-麩胺酸(LE)和絲胺酸-精胺酸(SR)的二肽。
在實施例中,所述多肽連接子包含天然存在的CoV S多肽或本文公開的CoV S多肽的1個與100個之間的連續胺基酸。在實施例中,所述多肽連接子具有對應於SEQ ID NO: 94的胺基酸序列。
在實施例中,所述CoV纖突(S)多肽包含折疊子。在實施例中,所述TMCT被折疊子替代。在實施例中,折疊子引起CoV纖突(S)多肽三聚化。在實施例中,所述折疊子是本領域已知的胺基酸序列。在實施例中,所述折疊子具有SEQ ID NO: 68的胺基酸序列。在實施例中,所述折疊子是T4次要纖維蛋白(fibritin)三聚化基序。在實施例中,T4次要纖維蛋白三聚化結構域具有SEQ ID NO: 103的胺基酸序列。在實施例中,所述折疊子的胺基酸序列通過多肽連接子與CoV纖突(S)多肽隔開。多肽連接子的非限制性例子見於整個本公開文本。
在實施例中,本公開文本提供了包含冠狀病毒S蛋白的片段的CoV S多肽以及包含所述多肽的奈米顆粒和疫苗。在實施例中,所述冠狀病毒S蛋白的片段的長度在約10個與約1500個胺基酸之間(例如長度為約10個、約20個、約30個、約40個、約50個、約60個、約70個、約80個、約90個、約100個、約150個、約200個、約250個、約300個、約350個、約400個、約450個、約500個、約550個、約600個、約650個、約700個、約750個、約800個、約850個、約900個、約950個、約1000個、約1050個、約1100個、約1150個、約1200個、約1250個、約1300個、約1350個、約1400個、約1450個或約1500個胺基酸)。在實施例中,所述冠狀病毒S蛋白的片段選自受體結合結構域(RBD)、亞結構域1、亞結構域2、上螺旋、融合肽、連接區、七肽重複區1、中央螺旋、七肽重複區2、NTD和TMCT。
在實施例中,所述CoV S多肽包含RBD和亞結構域1。在實施例中,包含RBD和亞結構域1的CoV S多肽是SEQ ID NO: 1的胺基酸319至591。
在實施例中,所述CoV S多肽含有冠狀病毒S蛋白的片段,其中所述冠狀病毒S蛋白的片段是RBD。RBD的非限制性例子包括SARS-CoV-2的RBD(胺基酸序列 = SEQ ID NO: 69)、SARS的RBD(胺基酸序列 = SEQ ID NO: 70)和MERS的RBD(胺基酸序列 = SEQ ID NO: 71)。
在實施例中,所述CoV S多肽含有通過多肽連接子連接的兩個或更多個RBD。在實施例中,所述多肽連接子具有SEQ ID NO: 90或SEQ ID NO: 94的胺基酸序列。
在實施例中,所述CoV S多肽含有1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19或20個RBD。
在一些實施例中,所述CoV S多肽含有通過多肽連接子連接的兩個或更多個SARS-CoV-2 RBD。在實施例中,含有兩個或更多個SARS-CoV-2 RBD的抗原具有對應於SEQ ID NO: 72-75之一的胺基酸序列。
在實施例中,所述CoV S多肽含有SARS-CoV-2 RBD和SARS RBD。在實施例中,所述CoV S多肽包含SARS-CoV-2 RBD和SARS RBD,其中各RBD由多肽連接子分開。在實施例中,包含SARS-CoV-2 RBD和SARS RBD的CoV S多肽具有選自SEQ ID NO: 76-79的胺基酸序列。
在實施例中,所述CoV S多肽含有SARS-CoV-2 RBD和MERS RBD。在實施例中,所述CoV S多肽包含SARS-CoV-2 RBD和MERS RBD,其中各RBD由多肽連接子分開。
在實施例中,所述CoV S多肽包含SARS RBD和MERS RBD。在實施例中,所述CoV S多肽包含SARS RBD和MERS RBD,其中各RBD由多肽連接子分開。
在實施例中,所述CoV S多肽包含SARS-CoV-2 RBD、SARS RBD和MERS RBD。在實施例中,所述CoV S多肽含有SARS-CoV-2 RBD、SARS RBD和MERS RBD,其中各RBD由多肽連接子分開。在實施例中,包含SARS-CoV-2 RBD、SARS RBD和MERS RBD的CoV S多肽具有選自SEQ ID NO: 80-83的胺基酸序列。
在實施例中,本文所述的CoV S多肽表現為具有N末端信號肽。在實施例中,所述N末端信號肽具有SEQ ID NO: 5(MFVFLVLLPLVSS)的胺基酸序列。在實施例中,所述N末端信號肽具有SEQ ID NO: 117(MFVFLVLLPLVSI)的胺基酸序列。在實施例中,所述N末端信號肽具有SEQ ID NO: 154(MFVFFVLLPLVSS)的胺基酸序列。在實施例中,所述信號肽可以被使得能夠表現CoV S蛋白的任何信號肽替代。在實施例中,CoV S蛋白信號肽胺基酸中的一個或多個可以被缺失或突變。保持起始的甲硫胺酸殘基以起始表現。在實施例中,所述CoV S多肽由選自以下的核酸序列編碼:SEQ ID NO: 35、SEQ ID NO: 37、SEQ ID NO: 95、SEQ ID NO: 43、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 53、SEQ ID NO: 55、SEQ ID NO: 57、SEQ ID NO: 96、SEQ ID NO: 60、SEQ ID NO: 131、SEQ ID NO: 135、SEQ ID NO: 142、SEQ ID NO: 145、SEQ ID NO: 148和SEQ ID NO: 150。在實施例中,相對于天然CoV纖突(S)信號多肽(SEQ ID NO: 5),所述CoV S多肽的N末端信號肽在Ser-13處含有突變。在實施例中,Ser-13被突變為任何天然胺基酸。在實施例中,Ser-13被突變為丙胺酸、甲硫胺酸、異白胺酸、白胺酸、蘇胺酸或擷胺酸。在實施例中,Ser-13被突變為異白胺酸。
所述CoV S蛋白在宿主細胞中表現後,N末端信號肽被切割以提供成熟CoV蛋白序列(SEQ ID NO: 2、4、38、41、44、48、51、54、58、61、63、65、67、73、75、78、79、82、83、85、87、89、106、110、132、133、114、138、141、144、147、151、153、156和158)。在實施例中,所述信號肽被宿主細胞蛋白酶切割。在多方面中,可以從宿主細胞中分離全長蛋白質,隨後切割信號肽。
在表現和純化期間從具有對應於SEQ ID NO: 1、3、36、40、42、46、49、52、56、59、62、64、66、72、74、76、77、80、81、84、86、87、105、107、88、109、130、134、136、137、140、143、146、149、152、155、157、159-163的胺基酸序列的CoV纖突(S)多肽中切割信號肽後,獲得具有選自SEQ ID NO: 2、4、38、41、44、48、51、54、58、61、63、65、67、73、75、78、79、82、83、85、106、108、89和110、112-115、132、133、114、138、141、144、147、151、153、156、158、164-168的胺基酸序列的成熟多肽,並且將其用於產生CoV S奈米顆粒疫苗或CoV S奈米顆粒。
有利地,相對于天然CoV纖突(S)蛋白,所公開的CoV S多肽可以具有增強的蛋白質表現和穩定性。
在實施例中,本文所述的CoV S多肽含有相對于天然冠狀病毒S蛋白(SEQ ID NO: 2)的進一步修飾。在實施例中,本文所述的冠狀病毒S蛋白展現出與天然冠狀病毒S蛋白至少80%、或至少90%、或至少95%、或至少97%、或至少99%的同一性。本領域技術人員將使用已知技術來計算重組冠狀病毒S蛋白與天然蛋白或本文所述的任何CoV S多肽的同一性百分比。例如,可以使用可線上獲得的工具CLUSTALW2或基本局部比對搜索工具(Basic Local Alignment Search Tool,BLAST)來計算同一性百分比。可以將以下默認參數用於CLUSTALW2配對比對:蛋白質權重矩陣 = Gonnet;空位開放 = 10;空位延伸 = 0.1。
在實施例中,本文所述的CoV S多肽的胺基酸序列與具有SEQ ID NO: 87的胺基酸序列的CoV S多肽至少91%、至少92%、至少93%、至少94%、95%、至少96%、至少97%、至少98%、至少99%、至少99.5%相同,或100%相同。CoV S多肽可以具有與具有SEQ ID NO: 87的胺基酸序列的CoV S多肽的胺基酸序列相比多至約1個、多至約2個、多至約3個、多至約4個、多至約5個、多至約10個、多至約15個、多至約20個、多至約25個、多至約30個、多至約35個、多至約40個、多至約45個、或多至約50個胺基酸的缺失、插入或突變。CoV S多肽可以具有與具有SEQ ID NO: 87的胺基酸序列的CoV S多肽相比在約1個與約5個之間的胺基酸、在約3個與約10個之間的胺基酸、在約5個與10個之間的胺基酸、在約8個與12個之間的胺基酸、在約10個與15個之間的胺基酸、在約12個與17個之間的胺基酸、在約15個與20個之間的胺基酸、在約18個與23個之間的胺基酸、在約20個與25個之間的胺基酸、在約22個與約27個之間的胺基酸、在約25個與30個之間的胺基酸、在約30個與35個之間的胺基酸、在約35個與40個之間的胺基酸、在約40個與45個之間的胺基酸、或在約45個與50個之間的胺基酸的缺失、插入或突變。在實施例中,本文所述的CoV S多肽與冠狀病毒S蛋白(SEQ ID NO: 87)相比包含約1個、約2個、約3個、約4個、約5個、約6個、約7個、約8個、約9個、約10個、約11個、約12個、約13個、約14個、約15個、約16個、約17個、約18個、約19個、約20個、約21個、約22個、約23個、約24或約25個取代。
在實施例中,本文所述的CoV S多肽與具有選自SEQ ID NO: 2、4、38、41、44、48、51、54、58、61、63、65、67、73、75、78、79、82、83、85、106、108、89和110、112-115、132、133、114、138、141、144、147、151、153、156和158、164-168中的任一個的胺基酸序列的CoV S多肽至少95%、至少96%、至少97%、至少98%、至少99%或至少99.5%相同。
在實施例中,所述冠狀病毒S多肽在N末端、C末端、或N末端和C末端兩者處延伸。在多方面中,所述延伸物是對諸如純化或檢測等功能有用的標籤。在多方面中,所述標籤含有表位。例如,所述標籤可以是多麩胺酸標籤、FLAG標籤、HA標籤、多His標籤(具有約5個-10個組胺酸)(SEQ ID NO: 101)、六組胺酸標籤(SEQ ID NO: 100)、8X-His標籤(具有八個組胺酸)(SEQ ID NO: 102)、Myc標籤、麩胱甘肽-S-轉移酶標籤、綠色螢光蛋白標籤、麥芽糖結合蛋白標籤、硫氧還蛋白標籤或Fc標籤。在其他方面,所述延伸物可以是與蛋白質融合以增強表現的N末端信號肽。儘管此類信號肽通常在細胞中表現期間被切割,但一些奈米顆粒可以含有具有完整信號肽的抗原。因此,當奈米顆粒包含抗原時,所述抗原可以含有延伸物,因此當摻入奈米顆粒中時可以是融合蛋白。出於計算與序列的同一性的目的,不包括延伸物。在實施例中,所述標籤是蛋白酶切割位點。蛋白酶切割位點的非限制性例子包括HRV3C蛋白酶切割位點、胰凝乳蛋白酶、胰蛋白酶、彈性蛋白酶、內肽酶、半胱天冬酶1、半胱天冬酶2、半胱天冬酶3、半胱天冬酶4、半胱天冬酶5、半胱天冬酶6、半胱天冬酶7、半胱天冬酶8、半胱天冬酶9、半胱天冬酶10、腸激酶、因子Xa、顆粒酶B、TEV蛋白酶和凝血酶。在實施例中,所述蛋白酶切割位點是HRV3C蛋白酶切割位點。在實施例中,所述蛋白酶切割位點包含SEQ ID NO: 98的胺基酸序列。
在實施例中,所述CoV S醣蛋白包含融合蛋白。在實施例中,所述CoV S醣蛋白包含N末端融合蛋白。在實施例中,所述CoV S醣蛋白包含C末端融合蛋白。在實施例中,所述融合蛋白涵蓋可用於蛋白質表現、純化或檢測的標籤。在實施例中,所述標籤是多His標籤(具有約5個-10個組胺酸)、Myc標籤、麩胱甘肽-S-轉移酶標籤、綠色螢光蛋白標籤、麥芽糖結合蛋白標籤、硫氧還蛋白標籤、Strep標籤、Twin-Strep標籤或Fc標籤。在實施例中,所述標籤是Fc標籤。在實施例中,所述Fc標籤是單體、二聚體或三聚體的。在實施例中,所述標籤是六組胺酸標籤,例如含有六個組胺酸的多His標籤(SEQ ID NO: 100)。在實施例中,所述標籤是具有SEQ ID NO: 99的胺基酸序列的Twin-Strep標籤。
在實施例中,所述CoV S多肽是包含另一種冠狀病毒蛋白的融合蛋白。在實施例中,所述另一種冠狀病毒蛋白來自相同的冠狀病毒。在實施例中,所述另一種冠狀病毒蛋白來自不同的冠狀病毒。
在多方面中,所述CoV S蛋白可以是截短的。例如,N末端可以被截短約10個胺基酸、約30個胺基酸、約50個胺基酸、約75個胺基酸、約100個胺基酸或約200個胺基酸。代替N末端或除了N末端之外,C末端可以是截短的。例如,C末端可以被截短約10個胺基酸、約30個胺基酸、約50個胺基酸、約75個胺基酸、約100個胺基酸或約200個胺基酸。出於計算與具有截短的蛋白質的同一性的目的,在蛋白質的剩餘部分上測量同一性。
含有 CoV 纖突( S )多肽的去污劑 - 核心奈米顆粒
在實施例中,本文公開的組合物包含含有CoV S多肽的去污劑-核心奈米顆粒,所述CoV S多肽與去污劑核心締合。
在實施例中,本公開文本的奈米顆粒包含成熟CoV S多肽。在實施例中,本公開文本的奈米顆粒包含與去污劑核心締合的CoV S多肽。去污劑的存在通過形成組織並呈遞抗原的核心來促進奈米顆粒的形成。在實施例中,所述奈米顆粒可以含有組裝成多寡聚醣蛋白-去污劑(例如PS80)奈米顆粒的CoV S多肽,其中頭部區域向外突出並且疏水區域和PS80去污劑形成被醣蛋白包圍的中央核心。在實施例中,所述CoV S多肽固有地含有或適於含有跨膜結構域以促進將所述蛋白質締合到去污劑核心中。在實施例中,所述CoV S多肽含有頭部結構域。主要地,CoV S多肽三聚體的跨膜結構域與去污劑締合;然而,多肽的其他部分也可以相互作用。有利地,所述奈米顆粒具有改善的對環境脅迫的抗性,使得由於在去污劑周圍組織蛋白質的多個拷貝,它們提供增強的穩定性和/或改善的對免疫系統的呈遞。
在實施例中,所述去污劑核心是非離子去污劑核心。在實施例中,所述CoV S多肽與非離子去污劑核心締合。在實施例中,所述去污劑選自聚山梨醇酯-20(PS20)、聚山梨醇酯-40(PS40)、聚山梨醇酯-60(PS60)、聚山梨醇酯-65(PS65)和聚山梨醇酯-80(PS80)。在實施例中,所述去污劑是PS80。
在實施例中,所述CoV S多肽形成三聚體。在實施例中,所述CoV S多肽奈米顆粒由圍繞非離子去污劑核心的多個多肽三聚體構成。在實施例中,所述奈米顆粒含有至少約1個或多個三聚體。在實施例中,所述奈米顆粒含有纖突蛋白的至少約5個三聚體至約30個三聚體。在實施例中,每個奈米顆粒可以含有1、2、3、4、5、6、7、8、9、10、11、12、或15、20、25或30個三聚體,包括在中間的所有值和範圍。本文所公開的組合物可以含有具有不同數量的三聚體的奈米顆粒。例如,組合物可以含有三聚體的數量範圍從2-9的奈米顆粒;在實施例中,組合物中的奈米顆粒可以含有2-6個三聚體。在實施例中,所述組合物含有奈米顆粒的異源群體,每個奈米顆粒具有2至6個三聚體,或者每個奈米顆粒具有2至9個三聚體。在實施例中,所述組合物可以含有基本上均質的奈米顆粒群體。例如,所述群體可以含有約95%的具有5個三聚體的奈米顆粒。
本文所公開的奈米顆粒的細微性具有一定範圍。在實施例中,本文所公開的奈米顆粒的細微性的Z-ave尺寸範圍為從約20 nm至約60 nm、約20 nm至約50 nm、約20 nm至約45 nm、約20 nm至約35 nm、約20 nm至約30 nm、約25 nm至約35 nm、或約25 nm至約45 nm。除非另外說明,否則使用Zetasizer NanoZS(Malvern,英國)通過動態光散射(DLS)來測量細微性(Z-ave)。
在實施例中,與包含野生型CoV S多肽的奈米顆粒相比,包含本文所公開的CoV S多肽的奈米顆粒具有減小的細微性。在實施例中,所述CoV S多肽的細微性小至少約40%,例如細微性小至少約40%、至少約45%、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%或至少約85%。
包含本文所公開的CoV S多肽的奈米顆粒在尺寸、形狀和質量方面比包含野生型CoV S多肽的奈米顆粒更均勻。多分散性指數(PDI)是異源性的度量,除非另外說明,否則使用Malvern Setasizer通過動態光散射來測量。在實施例中,本文所測量的顆粒具有約0.2至約0.45,例如約0.2、約0.25、約0.29、約0.3、約0.35、約0.40或約0.45的PDI。在實施例中,本文測量的奈米顆粒的PDI比包含野生型CoV S多肽的奈米顆粒的PDI小至少約25%,例如小至少約25%、至少約30%、至少約35%、至少約40%、至少約45%、至少約50%、至少約55%或至少約60%。
與野生型CoV S多肽或其奈米顆粒相比,所述CoV S多肽和包含所述多肽的奈米顆粒具有改善的熱穩定性。除非另外說明,否則使用差示掃描量熱法(DSC)來測量CoV S多肽的熱穩定性。轉變焓(ΔHcal)是使CoV S多肽展開所需的能量。在實施例中,與野生型CoV S多肽相比,所述CoV S多肽具有增加的ΔHcal。在實施例中,CoV S多肽的ΔHcal是野生型CoV S多肽的ΔHcal的約2倍、約3倍、約4倍、約5倍、約6倍、約7倍、約8倍、約9倍或約10倍。
在本文所公開的疫苗組合物中可以包括若干種奈米顆粒類型。在多方面中,所述奈米顆粒類型是以各向異性棒的形式,其可以是二聚體或單體。在其他方面,所述奈米顆粒類型是球形寡聚體。在又其他方面,所述奈米顆粒可以被描述為中間體奈米顆粒,其具有介於前兩種類型之間的沈降特性。可以通過控制產生過程期間的去污劑和蛋白質濃度來調節奈米顆粒類型的形成。可以通過測量沈降係數來確定奈米顆粒類型。
(ii) 至少三種 HA 醣蛋白
在實施例中,本公開文本的免疫原性組合物包含至少三種HA醣蛋白或至少四種HA醣蛋白。在實施例中,本公開文本的免疫原性組合物包含三種或四種HA醣蛋白。在實施例中,所述HA醣蛋白中的每一種來自不同的流感毒株。在實施例中,三種HA醣蛋白來自甲型流感毒株,並且一種HA醣蛋白來自乙型流感毒株。在實施例中,兩種HA醣蛋白來自甲型流感毒株,並且兩種HA醣蛋白來自乙型流感毒株。在實施例中,兩種HA醣蛋白來自甲型流感毒株,並且一種HA醣蛋白來自乙型流感毒株。
在實施例中,所述至少三種HA醣蛋白中的每一種是使用基於蛋的製造方法分別分離的。在實施例中,基於蛋的製造方法包括 (a) 在蛋中繁殖流感病毒和 (b) 收穫所述流感病毒。
在實施例中,所述流感病毒是活病毒。在實施例中,所述流感病毒是弱化的或“減毒的”病毒。在實施例中,所述流感病毒被優化以在蛋中生長。在實施例中,所述優化的流感病毒缺乏血凝素的多鹼基切割位點。以下文章詳細描述了優化的流感病毒(稱為“候選疫苗病毒”)的開發,並且通過引用以其整體併入本文:Belser等人 Virology. 2017年11月; 511: 135-141。
在實施例中,所述蛋是雞蛋。在實施例中,所述雞蛋是含胚雞蛋。在實施例中,所述蛋是無病原體的蛋。在實施例中,通過將病毒接種在含胚雞蛋的尿囊腔中來繁殖流感病毒。以下文章描述了示例性接種方法,並且通過引用以其整體併入本文:Brauer等人 J Vis Exp. 2015; (97): 52421。
在實施例中,所述基於蛋的製造方法包括純化所述流感病毒。在實施例中,使用以下技術中的任一種純化流感病毒:離心、層析、沈澱或奈米過濾。在實施例中,所述離心技術是超速離心。在實施例中,使用區帶離心純化所述病毒。在實施例中,所述區帶離心是連續流區帶離心。
在實施例中,所述基於蛋的製造方法包括滅活(本文也稱為“殺死”)流感病毒。在實施例中,使用低pH(例如,約3.5-5.5的pH)、熱、乙醇、紫外光、暴露於去污劑(例如,辛基苯酚)或暴露於化學品(例如,2-丙醇、乙醇、碘聚維酮)使流感病毒滅活。在實施例中,用紫外光、β丙內酯、去氧膽酸鈉、甲醛或其任何組合滅活純化的病毒。
在實施例中,所述基於蛋的製造方法包括將流感病毒暴露於表面活性劑。所述表面活性劑可以是牛磺去氧膽酸鈉、辛基酚乙氧基化物(Triton®-X 100)或十六烷基三甲基溴化銨。將流感病毒暴露於表面活性劑導致流感裂解病毒粒子的形成。在實施例中,所述至少三種HA醣蛋白處於流感裂解病毒粒子的形式。
在實施例中,所述基於蛋的製造方法包括從病毒中純化流感抗原(例如,血凝素)。
以下食品和藥物管理局(FDA)批准的流感疫苗是使用基於蛋的製造方法生產的:AFLURIA® QUADRIVALENT、FLUARIX® QUADRIVALENT、FLULAVAL QUADRIVALENT、FLUZONE® QUADRIVALENT、FLUZONE® HIGH-DOSE QUADRIVALENT、FLUMIST® QUADRIVALENT、FLUAD®和FLUAD® QUADRIVALENT。
在實施例中,所述至少三種HA醣蛋白中的每一種是使用基於細胞培養的方法分離的。在實施例中,基於細胞培養的方法包括 (i) 使流感病毒在細胞中生長和 (ii) 從所述細胞中收穫所述病毒。在實施例中,基於細胞培養的方法包括 (i) 用包含血凝素的載體轉染細胞和 (ii) 從所述細胞收穫所述血凝素。在實施例中,基於細胞培養的方法包括 (i) 用編碼血凝素的病毒轉導細胞和 (ii) 從所述細胞收穫所述血凝素。在實施例中,所收穫的血凝素是重組血凝素。
在實施例中,所述細胞是動物細胞、細菌細胞、昆蟲細胞或真菌細胞。在實施例中,所述動物是人、鳥(例如,雞)、犬、爬行動物、山羊、豬、小鼠、兔或大鼠。
在實施例中,所述編碼血凝素的病毒是杆狀病毒、慢病毒或腺相關病毒。
在實施例中,純化使用基於細胞培養的方法產生的流感病毒。描述的純化使用基於蛋的製造方法生產的流感病毒的任何純化技術可以用於純化使用基於細胞培養的方法生產的流感病毒。
在實施例中,純化使用基於細胞培養的方法生產的血凝素。純化技術包括層析、離心、沈澱和奈米過濾。
食品和藥品管理局(FDA)批准的流感疫苗FLUCELVAX® QUADRIVALENT是使用基於細胞培養的方法生產的。
在實施例中,所述至少三種HA醣蛋白中的每一種是重組血凝素。食品和藥品管理局(FDA)批准的流感疫苗FLUBLOK® QUADRIVALENT是重組血凝素。
在實施例中,所述至少三種血凝素處於重組血凝素的形式。從產生血凝素的細胞中分離重組血凝素。在實施例中,已用編碼血凝素的載體轉染產生血凝素的細胞。在實施例中,已用編碼血凝素的病毒轉導產生血凝素的細胞。
(iia) 至少三種包含血凝素的 HA 醣蛋白 - 去污劑 - 核心奈米顆粒
在實施例中,本文公開的組合物包含含有來自流感病毒的血凝素的去污劑-核心奈米顆粒。上述去污劑-核心奈米顆粒詳細描述於美國專利號10,426,829中,其出於所有目的通過引用以其整體併入本文。
去污劑-核心奈米顆粒包含來自流感病毒的血凝素,所述血凝素與去污劑核心締合。在實施例中,所述血凝素是三聚體。每個奈米顆粒可以含有1、2、3、4、5、6、7、8、9、10、11、12、13、14個或15個三聚體。在實施例中,所述奈米顆粒含有在約2個至約9個之間、在約2個至約6個之間、或約5個血凝素三聚體。所述血凝素與所述奈米顆粒的含非離子去污劑的核心締合。在實施例中,所述去污劑選自聚山梨醇酯-20(PS20)、聚山梨醇酯-40(PS40)、聚山梨醇酯-60(PS60)、聚山梨醇酯-65(PS65)和聚山梨醇酯-80(PS80)。去污劑的存在通過形成組織並呈現抗原的核心促進奈米顆粒的形成。在實施例中,所述奈米顆粒可以含有組裝成多寡聚醣蛋白-PS80蛋白-去污劑奈米顆粒的抗原,其中頭部區域向外突出並且疏水區域和PS80去污劑形成被抗原包圍的中央核心。
本文所公開的奈米顆粒的Z-ave尺寸範圍為從約20 nm至約60 nm、約20 nm至約50 nm、約20 nm至約45 nm或約25 nm至約45 nm。
在實施例中,去污劑-核心奈米顆粒通過以下方式產生於昆蟲細胞中:使用杆狀病毒表現系統表現HA蛋白並用去污劑提取HA蛋白。在純化期間,將第一去污劑交換為第二去污劑(通常是非離子去污劑),產生具有非離子去污劑核心的奈米顆粒,三聚體形式的HA蛋白的跨膜結構域嵌入其中。
圖 7(左小圖)展示了如在電子顯微鏡下觀察到的這些結構。
包含在本文所述的去污劑-核心奈米顆粒或HaSMaN中的血凝素可以來自任何流感病毒株。在美國,幾乎每個冬季,人甲型和乙型流感病毒都會引起季節性疾病流行。
所述HA蛋白可以選自亞型H1、H2、H3、H4、H5、H6、H7、H8、H9、H10、H11、H12、H13、H14、H15、H16、H17和H18。在系統發生學上,流感被分成多個組。對於HA,組1含有H1、H2、H5、H6、H8、H9、H11、H12、H13、H16、H17和H18,並且組2含有H3、H4、H7、H10、H14和H15。
在實施例中,所述去污劑-核心奈米顆粒或HaSMaN是使用中性pH純化產生的胰蛋白酶抗性奈米顆粒。在HA奈米顆粒的純化和配製期間,通過高於6.9至8.5的中性pH範圍實現胰蛋白酶抗性。胰蛋白酶抗性流感醣蛋白和胰蛋白酶抗性流感奈米顆粒;及其製造方法在美國專利號10,426,829中有詳細描述。
在實施例中,本文所述的去污劑-核心奈米顆粒或HaSMaN的血凝素包含全長野生型血凝素胺基酸序列。在實施例中,所述血凝素是血凝素變體。在實施例中,所述血凝素展現出與野生型血凝素蛋白至少80%、至少85%、至少90%、至少95%、至少97%、至少98%或至少99%的同一性。可以使用比對程式ClustalW2(可獲自www.ebi.ac.uk/Tools/msa/clustalw2/)來計算同一性百分比。可以將以下默認參數用於配對比對:蛋白權重矩陣(Protein Weight Matrix)= Gonnet;空位開放 = 10;空位延伸 = 0.1。
HA是每個單體由約550個胺基酸殘基組成的同三聚體。HA的每個單體在概念上已被分成三個結構域:約515個殘基的胞外域構成了分子的病毒外部分;27個殘基的單延伸段限定了跨膜(TM)結構域;並且約10個殘基構成胞質尾(CT)。雖然可以對血凝素進行一些改變,但去污劑核心奈米顆粒和HaSMaN兩者的形成均需要完整的跨膜結構域(TM)。因此,在特定實例中,修飾的HA蛋白序列與野生型TM和CT結構域具有100%同一性,在剩餘的胞外域部分具有一定的靈活性,其中同一性可以是至少90%或至少95%。這些結構域可以通過與Melikyan等人(Mol Biol Cell. 1999年6月; 10(6): 1821-1836)的圖1中所示的日本/305/57 HA的TM結構域和CT的胺基酸序列的同源性來鑒定,但是應該注意在胞外域、TM和CT結構域之間的邊界可以在HA蛋白之間變化多至三個胺基酸。
(iib) 流感疫苗 -HaSMaN (血凝素皂苷基質奈米顆粒)
在實施例中,本文所述的免疫原性組合物和疫苗組合物包含HaSMaN(血凝素皂苷基質奈米顆粒)。
圖 7(右小圖)展示了如在電子顯微鏡下觀察到的HaSMaN結構。HA醣蛋白裝飾基質籠樣結構。通過製備包含來自流感病毒的血凝素的去污劑-核心奈米顆粒,然後將它們與ISCOM基質佐劑顆粒一起培育一段時間,形成HaSMaN結構。ISCOM基質顆粒示於
圖 7的中小圖中。值得注意地,HaSMaN易於用甲型流感HA蛋白形成,但不易於用乙型流感HA蛋白形成。
通過將去污劑-核心奈米顆粒與包含皂苷級分、膽固醇和磷脂的ISCOM基質佐劑一起培育來產生本文所公開的HaSMaN。在實施例中,通過將去污劑-核心奈米顆粒與ISCOM基質佐劑一起培育約24小時與約48小時之間來形成HaSMaN。例如,可以將所述去污劑-核心奈米顆粒與ISCOM基質佐劑一起培育約24小時、約25小時、約26小時、約27小時、約28小時、約29小時、約30小時、約31小時、約32小時、約33小時、約34小時、約35小時、約36小時、約37小時、約38小時、約39小時、約40小時、約41小時、約42小時、約43小時、約44小時、約45小時、約46小時、約47小時、約48小時或更長時間。在一些實施例中,通過將去污劑-核心奈米顆粒與ISCOM基質佐劑一起培育至少約24小時、至少約25小時、至少約26小時、至少約27小時、至少約28小時、至少約29小時、至少約30小時、至少約31小時、至少約32小時、至少約33小時、至少約34小時、至少約35小時、至少約36小時、至少約37小時、至少約38小時、至少約39小時、至少約40小時、至少約41小時、至少約42小時、至少約43小時、至少約44小時、至少約45小時、至少約46小時、至少約47小時或至少約48小時來形成HaSMaN。在實施例中,通過在約4ºC至約25ºC的溫度下培育去污劑-核心奈米顆粒與ISCOM基質佐劑來形成HaSMaN。例如,可以通過在約4ºC、約5ºC、約6ºC、約7ºC、約8ºC、約9ºC、約10ºC、約11ºC、約12ºC、約13ºC、約14ºC、約15ºC、約16ºC、約17ºC、約18ºC、約19ºC、約20ºC、約21ºC、約22ºC、約23ºC、約24ºC、約25ºC或更高的溫度下培育去污劑-核心奈米顆粒與ISCOM基質佐劑來形成HaSMaN。在實施例中,通過在至少約4ºC、至少約5ºC、至少約6ºC、至少約7ºC、至少約8ºC、至少約9ºC、至少約10ºC、至少約11ºC、至少約12ºC、至少約13ºC、至少約14ºC、至少約15ºC、至少約16ºC、至少約17ºC、至少約18ºC、至少約19ºC、至少約20ºC、至少約21ºC、至少約22ºC、至少約23ºC、至少約24ºC、至少約25ºC的溫度下培育去污劑-核心奈米顆粒與ISCOM基質佐劑來形成HaSMaN。通常,在4ºC或25ºC下培育約24小時-48小時是形成所需要的。HaSMaN的形成由較高的溫度促進。在實施例中,通過在約25ºC下培育去污劑-核心奈米顆粒與ISCOM基質佐劑至少24小時來進行HaSMaN的形成。在投予於受試者之前不久,將去污劑核心奈米顆粒與ISCOM基質佐劑混合(即床邊混合)不會產生HaSMaN。更長的培育時間段不會負面地影響HaSMaN形成。
去污劑 - 核心奈米顆粒的產生
本公開文本的奈米顆粒是非天然存在的產物,其組分在自然界中不會一起出現。在實施例中,本文所公開的方法使用去污劑交換方法,其中使用第一去污劑來分離蛋白質,然後將該第一去污劑交換成第二去污劑以形成奈米顆粒。
所述奈米顆粒中所含的抗原通常通過在宿主細胞中重組表現而產生。可以使用標準重組技術。在實施例中,使用杆狀病毒系統在昆蟲宿主細胞中表現所述CoV S多肽。在實施例中,所述杆狀病毒是組織蛋白酶-L敲除的杆狀病毒、幾丁質酶敲除的杆狀病毒。任選地,所述杆狀病毒是組織蛋白酶-L和幾丁質酶兩者的雙重敲除。在昆蟲細胞表現系統中可以獲得高水準的表現。昆蟲細胞的非限制性例子是草地貪夜蛾(Spodoptera frugiperda)(Sf)細胞(例如Sf9、Sf21)、粉紋夜蛾(Trichoplusiani)細胞(例如High Five細胞)和果蠅(Drosophila)S2細胞。在實施例中,在任何合適的宿主細胞中產生本文所述的CoV S多肽或血凝素。在實施例中,所述宿主細胞是昆蟲細胞。在實施例中,所述昆蟲細胞是Sf9細胞。
典型的轉染和細胞生長方法可以用於培養所述細胞。可以根據本領域熟知的方法將載體(例如,包含編碼融合蛋白的多核苷酸的載體)轉染到宿主細胞中。例如,可以通過磷酸鈣共沈澱、電穿孔、顯微注射、脂質體轉染和採用多胺轉染試劑的轉染來實現將核酸引入真核細胞中。在一個實施例中,所述載體是重組杆狀病毒。
使宿主細胞生長的方法包括但不限於分批、補料分批、連續和灌注細胞培養技術。細胞培養意指細胞在生物反應器(發酵室)中的生長和繁殖,在所述生物反應器中細胞繁殖並表現蛋白質(例如重組蛋白)以用於純化和分離。通常,細胞培養是在生物反應器中在無菌、受控的溫度和大氣條件下進行。生物反應器是可以監測環境條件如溫度、大氣、攪拌和/或pH的用於培養細胞的室。在一個實施例中,所述生物反應器是不銹鋼室。在另一個實施例中,所述生物反應器是預滅菌的塑膠袋(例如Cellbag®,Wave Biotech,新澤西州布裡奇沃特)。在其他實施例中,所述預滅菌的塑膠袋是約50 L至3500 L的袋。
奈米顆粒的提取和純化
在宿主細胞生長後,可以使用去污劑和純化方案從宿主細胞中收穫所述蛋白質或奈米顆粒。一旦宿主細胞已生長48小時至96小時,則從培養基中分離細胞,並且添加含去污劑的溶液以溶解細胞膜,從而使蛋白質釋放到去污劑提取物中。Triton X-100和TERGITOL®壬基酚乙氧基化物(也稱為NP-9)各自是用於提取的優選去污劑。可以將去污劑添加至約0.1%至約1.0%的最終濃度。例如,所述濃度可以為約0.1%、約0.2%、約0.3%、約0.5%、約0.7%、約0.8%或約1.0%。範圍可以是約0.1%至約0.3%。在實施例中,所述濃度為約0.5%。
在實施例方面中,不同的第一去污劑可以用於從宿主細胞中分離所述蛋白質。例如,所述第一去污劑可以是雙(聚乙二醇雙[咪唑基羰基])、壬苯醇醚-9、雙(聚乙二醇雙[咪唑基羰基])、BRIJ®聚乙二醇十二烷基醚35、BRIJ®聚乙二醇 (3) 十六烷基醚56、BRIJ®醇乙氧基化物72、BRIJ®聚乙二醇2硬脂基醚76、BRIJ®聚乙二醇單油烯基醚92V、BRIJ®聚氧乙烯 (10) 油烯基醚97、BRIJ®聚乙二醇十六烷基醚58P、CREMOPHOR® EL蓖麻油聚氧乙烯醚、十乙二醇單十二烷基醚、N-癸醯基-N-甲基葡糖胺、正癸基α-D吡喃葡萄糖苷、癸基β-D-麥芽吡喃糖苷、正十二烷醯基-N-甲基葡糖醯胺、正十二烷基α-D-麥芽糖苷、正十二烷基β-D-麥芽糖苷、正十二烷基β-D-麥芽糖苷、七乙二醇單癸基醚、七乙二醇單十二烷基醚、七乙二醇單十四烷基醚、正十六烷基β-D-麥芽糖苷、六乙二醇單十二烷基醚、六乙二醇單十六烷基醚、六乙二醇單十八烷基醚、六乙二醇單十四烷基醚、Igepal CA-630、Igepal CA -630、甲基-6-0-(N-庚基胺基甲醯基)-α-D-吡喃葡萄糖苷、九乙二醇單十二烷基醚、N-壬醯基-N-甲基葡糖胺、N-壬醯基N-甲基葡糖胺、八乙二醇單癸基醚、八乙二醇單十二烷基醚、八乙二醇單十六烷基醚、八乙二醇單十八烷基醚、八乙二醇單十四烷基醚、辛基-β-D吡喃葡萄糖苷、五乙二醇單癸基醚、五乙二醇單十二烷基醚、五乙二醇單十六烷基醚、五乙二醇單己基醚、五乙二醇單十八烷基醚、五乙二醇單辛基醚、聚乙二醇二縮水甘油醚、聚乙二醇醚W-1、聚氧乙烯10十三烷基醚、聚氧乙烯100硬脂酸酯、聚氧乙烯20異十六烷基醚、聚氧乙烯20油烯基醚、聚氧乙烯40硬脂酸酯、聚氧乙烯50硬脂酸酯、聚氧乙烯8硬脂酸酯、聚氧乙烯雙(咪唑基羰基)、聚氧乙烯25丙二醇硬脂酸酯、皂草苷(Saponin from Quillaja bark)、SPAN® 20脫水山梨糖醇月桂酸酯、SPAN® 40脫水山梨糖醇單棕櫚酸酯、SPAN® 60脫水山梨糖醇硬脂酸酯、SPAN® 65脫水山梨糖醇三硬脂酸酯、SPAN® 80脫水山梨糖醇單油酸酯、SPAN® 85脫水山梨糖醇三油酸酯、TERGITOL®仲醇乙氧基化物15-S-12型、TERGITOL®仲醇乙氧基化物15-S-30型、TERGITOL®仲醇乙氧基化物15-S-5型、TERGITOL®仲醇乙氧基化物15-S-7型、TERGITOL®仲醇乙氧基化物15-S-9型、TERGITOL®壬基酚乙氧基化物NP-10型、TERGITOL®壬基酚乙氧基化物NP-4型、TERGITOL®壬基酚乙氧基化物NP-40型、TERGITOL®壬基酚乙氧基化物NP-7型、TERGITOL®壬基酚乙氧基化物NP-9型、TERGITOL®支鏈仲醇乙氧基化物TMN-10型、TERGITOL®支鏈仲醇乙氧基化物TMN-6型、TRITON
TMX-100聚乙二醇叔辛基苯基醚或其組合。
然後可以使用離心從細胞碎片中分離所述奈米顆粒。在實施例中,可以使用諸如採用氯化銫、蔗糖和碘克沙醇的梯度離心。其他技術可以用作替代或補充,例如標準純化技術,包括例如離子交換層析、親和層析和凝膠過濾層析。
例如,第一柱可以是離子交換層析樹脂,諸如FRACTOGEL® EMD基於甲基丙烯酸酯的聚合物珠TMAE(EMD Millipore);第二柱可以是小扁豆(Lens culinaris)凝集素親和樹脂;並且第三柱可以是陽離子交換柱,諸如FRACTOGEL® EMD基於甲基丙烯酸酯的聚合物珠SO3(EMD Millipore)樹脂。在其他方面,陽離子交換柱可以是MMC柱或Nuvia C Prime柱(Bio-Rad Laboratories, Inc)。優選地,本文所公開的方法不使用去污劑提取柱;例如疏水相互作用柱。這樣的柱通常在純化期間用於去除去污劑,但可能對此處公開的方法產生負面影響。
在實施例中,用於從宿主細胞中提取蛋白質的第一去污劑基本上被第二去污劑替代以得到奈米顆粒結構。在實施例中,所述第一去污劑是NP-9。通常,當通過HPLC測量時,所述奈米顆粒不含可檢測的NP-9。所述第二去污劑通常選自PS20、PS40、PS60、PS65和PS80。在實施例中,所述第二去污劑是PS80。
在實施例中,使用親和層析以結合醣蛋白(經由其碳水化合物部分)來進行去污劑交換。例如,親和層析可以使用豆類凝集素柱。豆類凝集素是最初在植物中鑒定出的蛋白質,並且發現其與碳水化合物殘基特異性地且可逆地相互作用。參見例如,Sharon和Lis, “Legume lectins--a large family of homologous proteins,” FASEB J. 1990年11月;4(14):3198-208;Liener, “The Lectins: Properties, Functions, and Applications in Biology and Medicine,” Elsevier, 2012。合適的凝集素包括伴刀豆球蛋白A(con A)、豌豆凝集素、紅豆草凝集素和小扁豆凝集素。小扁豆凝集素由於其結合特性是用於去污劑交換的優選柱。凝集素柱可商購獲得;例如,Capto小扁豆凝集素可以從GE Healthcare獲得。在某些方面,小扁豆凝集素柱可以使用重組凝集素。在分子水準上,認為碳水化合物部分與小扁豆凝集素結合,釋放蛋白質的胺基酸以在去污劑周圍聚結,導致形成去污劑核心,從而提供具有多個抗原拷貝(例如,醣蛋白寡聚體)的奈米顆粒,所述醣蛋白寡聚體可以是錨定在去污劑中的二聚體、三聚體或四聚體。在實施例中,所述CoV S多肽和/或血凝素形成三聚體。在實施例中,所述CoV S多肽三聚體和/或血凝素錨定在去污劑中。在實施例中,每個奈米顆粒含有至少一個與非離子核心締合的三聚體。
當在去污劑交換期間與蛋白質一起培育形成奈米顆粒時,去污劑在早期純化步驟期間可以以多至約0.1%(w/v)存在,並且使此量降低以獲得具有最佳穩定性的最終奈米顆粒。例如,所述非離子去污劑(例如,PS80)可以是約0.005%(v/v)至約0.1%(v/v),例如約0.005%(v/v)、約0.006%(v/v)、約0.007%(v/v)、約0.008%(v/v)、約0.009%(v/v)、約0.01%(v/v)、約0.015%(v/v)、約0.02%(v/v)、約0.025%(v/v)、約0.03%(v/v)、約0.035%(v/v)、約0.04%(v/v)、約0.045%(v/v)、約0.05%(v/v)、約0.055%(v/v)、約0.06%(v/v)、約0.065%(v/v)、約0.07%(v/v)、約0.075%(v/v)、約0.08%(v/v)、約0.085%(v/v)、約0.09%(v/v)、約0.095%(v/v)或約0.1%(v/v)PS80。在實施例中,所述奈米顆粒含有約0.03%至約0.05% PS80。在實施例中,所述奈米顆粒含有約0.01%(v/v)PS80。
在實施例中,對經純化的CoV S多肽和/或血凝素進行透析。在實施例中,在純化後進行透析。在實施例中,在包含磷酸鈉、NaCl和PS80的溶液中對所述CoV S多肽和/或血凝素進行透析。在實施例中,包含磷酸鈉的透析溶液含有在約5 mM與約100 mM之間的磷酸鈉,例如約5 mM、約10 mM、約15 mM、約20 mM、約25 mM、約30 mM、約35 mM、約40 mM、約45 mM、約50 mM、約55 mM、約60 mM、約65 mM、約70 mM、約75 mM、約80 mM、約85 mM、約90 mM、約95 mM或約100 mM磷酸鈉。在實施例中,包含磷酸鈉的溶液的pH為約6.5、約6.6、約6.7、約6.8、約6.9、約7.0、約7.1、約7.2、約7.3、約7.4或約7.5。在實施例中,包含氯化鈉的透析溶液包含約50 mM NaCl至約500 mM NaCl,例如約50 mM、約60 mM、約70 mM、約80 mM、約90 mM、約100 mM、約110 mM、約120 mM、約130 mM、約140 mM、約150 mM、約160 mM、約170 mM、約180 mM、約190 mM、約200 mM、約210 mM、約220 mM、約230 mM、約240 mM、約250 mM、約260 mM、約270 mM、約280 mM、約290 mM、約300 mM、約310 mM、約320 mM、約330 mM、約340 mM、約350 mM、約360 mM、約370 mM、約380 mM、約390 mM、約400 mM、約410 mM、約420 mM、約430 mM、約440 mM、約450 mM、約460 mM、約470 mM、約480 mM、約490 mM或約500 mM NaCl。在實施例中,包含PS80的透析溶液包含約0.005%(v/v)、約0.006%(v/v)、約0.007%(v/v)、約0.008%(v/v)、約0.009%(v/v)、約0.01%(v/v)、約0.015%(v/v)、約0.02%(v/v)、約0.025%(v/v)、約0.03%(v/v)、約0.035%(v/v)、約0.04%(v/v)、約0.045%(v/v)、約0.05%(v/v)、約0.055%(v/v)、約0.06%(v/v)、約0.065%(v/v)、約0.07%(v/v)、約0.075%(v/v)、約0.08%(v/v)、約0.085%(v/v)、約0.09%(v/v)、約0.095%(v/v)或約0.1%(v/v)PS80。在實施例中,所述透析溶液包含約25 mM磷酸鈉(pH 7.2)、約300 mM NaCl和約0.01%(v/v)PS80。
可以使用如下蛋白質進行去污劑交換,將所述蛋白質如上文所討論地純化,並且純化、冷凍儲存,然後解凍以進行去污劑交換。
本文所公開的組合物的穩定性可以按多種方式測量。在一種方法中,可以製備肽圖譜,以在設計成通過類比苛刻的儲存條件來脅迫奈米顆粒的各種處理後確定抗原蛋白的完整性。因此,穩定性的度量是與對照樣品相比脅迫樣品中抗原肽的相對豐度。例如,可以通過將含有CoV S多肽的奈米顆粒暴露於各種pH、蛋白酶、鹽、氧化劑(包括但不限於過氧化氫)、各種溫度、冷凍/解凍循環和攪拌來評價所述奈米顆粒的穩定性。
(iic) 至少三種血凝素:滅活的全流感病毒
在實施例中,所述至少三種血凝素處於全流感病毒的形式。全流感病毒包含其包膜、病毒膜、核衣殼和遺傳物質的全部。在實施例中,如本公開文本通篇所述,所述全流感病毒是滅活的。
(iid) 至少三種血凝素:從流感病毒提取的血凝素組合物
在實施例中,所述至少三種血凝素處於從流感病毒提取的血凝素組合物的形式。在實施例中,所述從流感病毒提取的血凝素組合物是流感裂解病毒粒子組合物或亞單位流感病毒組合物。
流感裂解病毒粒子是具有已用表面活性劑破壞的流感病毒膜的流感病毒。在實施例中,所述表面活性劑是本文所述的任何表面活性劑。在實施例中,所述表面活性劑是牛磺去氧膽酸鈉、辛基酚乙氧基化物(Triton®-X 100)或十六烷基三甲基溴化銨。在實施例中,使用基於蛋或基於細胞培養的製造方法產生所述流感裂解病毒粒子。在實施例中,通過以下方式產生流感裂解病毒粒子:在馬丁達比犬腎(Madin Darby Canine Kidney,MDCK)細胞中繁殖流感病毒,用β-丙內酯滅活病毒,將病毒暴露於去污劑十六烷基三甲基溴化銨,以及純化病毒粒子。
與流感裂解病毒粒子一樣,通過用表面活性劑破壞流感病毒膜產生亞單位流感病毒組合物。然而,與流感裂解病毒粒子不同,所述亞單位流感病毒組合物經受另外的純化。在實施例中,通過不同的沈降以去除內部亞病毒核心來純化所述亞單位流感病毒組合物。在實施例中,通過離心、層析、沈澱或奈米過濾來純化所述亞單位流感病毒組合物。所述表面活性劑可以是本文所述的任何表面活性劑。在實施例中,所述表面活性劑是牛磺去氧膽酸鈉、辛基酚乙氧基化物(Triton®-X 100)或十六烷基三甲基溴化銨。在實施例中,使用基於蛋或基於細胞培養的製造方法產生所述亞單位流感疫苗。
在實施例中,從病毒提取的血凝素組合物包含血凝素,並且排除病毒核糖核蛋白(vRNP)、基質蛋白M1和病毒包膜。
在實施例中,從病毒提取的血凝素組合物通過以下步驟獲得:(i) 使用基於蛋的製造方法產生全流感病毒;(ii) 通過離心和過濾收穫並澄清所述全流感病毒;(iii) 用甲醛滅活所述流感病毒;(iv) 通過區帶離心來濃縮和純化所述滅活的流感病毒;以及 (v) 在十六烷基三甲基溴化銨的存在下離心所述滅活的流感病毒。
免疫原性組合物配製品
本公開文本提供了免疫原性組合物,其含有 (i) 至少三種血凝素(HA)醣蛋白,其中所述三種HA醣蛋白來自不同的流感毒株;(ii) 處於去污劑-核心奈米顆粒形式的CoV S多肽,其中所述去污劑是非離子去污劑;以及 (iii) 醫藥上可接受的緩衝液。在實施例中,所述至少三種HA醣蛋白處於選自以下的形式:(a) 包含血凝素(HA)的去污劑-核心奈米顆粒;(b) HaSMaN(血凝素皂苷基質奈米顆粒);(c) 流感裂解病毒粒子;(d) 全流感病毒;(e) 重組血凝素,以及 (f) 從病毒提取的血凝素組合物。在實施例中,所述免疫原性組合物可以含有具有抗原的奈米顆粒,所述抗原來自同一病毒物種的多於一種病毒株。
在實施例中,所述免疫原性組合物包含 (i) 處於去污劑-核心奈米顆粒形式的CoV S多肽,其中所述去污劑是非離子去污劑,(ii) 至少三種血凝素(HA)醣蛋白,其中所述三種HA醣蛋白來自不同的流感毒株,其中所述至少三種HA醣蛋白處於包含HA醣蛋白的去污劑-核心奈米顆粒和HaSMaN的形式。在實施例中,所述免疫原性組合物包含 (i) 至少三種血凝素(HA)醣蛋白,其中所述三種HA醣蛋白來自不同的流感毒株,其中所述至少三種HA醣蛋白處於流感裂解病毒粒子的形式,以及 (ii) 處於去污劑-核心奈米顆粒形式的CoV S多肽,其中所述去污劑是非離子去污劑。在實施例中,所述免疫原性組合物包含 (i) 至少三種血凝素(HA)醣蛋白,其中所述三種HA醣蛋白來自不同的流感毒株,其中所述至少三種HA醣蛋白處於從病毒提取的血凝素組合物的形式,以及 (ii) 處於去污劑-核心奈米顆粒形式的CoV S多肽,其中所述去污劑是非離子去污劑。
在實施例中,所述組合物包含總共在約1種與約10種之間的包含血凝素的去污劑-核心奈米顆粒和HaSMaN,例如,總共約1種、約2種、約3種、約4種、約5種、約6種、約7種、約8種、約9種或約10種奈米顆粒。在實施例中,每種去污劑-核心奈米顆粒和HaSMaN含有來自不同流感毒株的血凝素。在實施例中,每種HaSMaN含有來自甲型流感毒株的血凝素。在實施例中,來自每種去污劑-核心奈米顆粒的血凝素來自乙型流感毒株。在實施例中,每種HaSMaN含有來自乙型流感毒株的血凝素。在實施例中,來自每種去污劑-核心奈米顆粒的血凝素來自甲型流感毒株。在實施例中,來自每種去污劑-核心奈米顆粒的血凝素來自乙型流感毒株,並且來自每種HaSMaN的血凝素來自甲型流感毒株。在實施例中,所述組合物包含總共四種包含血凝素的去污劑-核心奈米顆粒和HaSMaN。在實施例中,所述組合物包含總共三種包含血凝素的去污劑-核心奈米顆粒和HaSMaN。
在另一個實施例中,本公開文本提供了包含一個或多個容器的藥物包裝或套組,所述一個或多個容器裝有所述免疫原性組合物的一種或多種組分。
本文所公開的組合物可以預防性地或治療性地使用,但是通常將是預防性的。因此,本公開文本包括用於治療或預防感染的方法。所述方法涉及向受試者投予治療量或預防量的本公開文本的免疫原性組合物。在實施例中,所述藥物組合物是提供保護作用的疫苗組合物。在實施例中,所述保護作用包括在一定百分比的暴露群體中改善與感染相關的症狀。例如,與未經治療的受試者相比,所述組合物可以預防或減輕選自以下的一種或多種病毒疾病症狀:發熱、疲勞、肌肉疼痛、頭痛、喉嚨痛、嘔吐、腹瀉、皮疹、腎和肝功能受損的症狀、內出血和外出血。
可以在存在各種賦形劑、緩衝液等的情況下將所述奈米顆粒配製用於作為疫苗投予。例如,所述疫苗組合物可以含有磷酸鈉、氯化鈉和/或組胺酸。磷酸鈉可以按約10 mM至約50 mM、約15 mM至約25 mM、或約25 mM存在;在特定情況下,存在約22 mM的磷酸鈉。組胺酸可以以約0.1%(w/v)、約0.5%(w/v)、約0.7%(w/v)、約1%(w/v)、約1.5%(w/v)、約2%(w/v)或約2.5%(w/v)存在。氯化鈉(當存在時)可以為約150 mM。在某些組合物中,氯化鈉可以按較高濃度(例如從約200 mM至約500 mM)存在。在實施例中,氯化鈉以高濃度(包括但不限於約200 mM、約250 mM、約300 mM、約350 mM、約400 mM、約450 mM或約500 mM)存在。
在實施例中,本文所述的奈米顆粒在某些pH水準下具有改善的穩定性。在實施例中,所述奈米顆粒在微酸性pH水準下是穩定的。例如,所述奈米顆粒在微酸性pH(例如從pH 5.8至pH 7.0)下是穩定的。在實施例中,所述奈米顆粒和含有奈米顆粒的組合物在範圍從約pH 5.8至約pH 7.0的pH(包括約pH 5.9至約pH 6.8、約pH 6.0至約pH 6.5、約pH 6.1至約pH 6.4、約pH 6.1至約pH 6.3或約pH 6.2)下可以是穩定的。在實施例中,本文所述的奈米顆粒和組合物在中性pH(包括從約pH 7.0至約pH 7.4)下是穩定的。在實施例中,本文所述的奈米顆粒和組合物在微鹼性pH(例如從約pH 7.0至約pH 8.5、從約pH 7.0至約pH 8.0或從約pH 7.0至約pH 7.5,包括在中間的所有值和範圍)下是穩定的。
佐劑
在某些實施例中,本文所公開的組合物可以與一種或多種佐劑組合以增強免疫反應。在實施例中,所述組合物是在沒有佐劑的情況下製備的,因此可用來作為無佐劑組合物投予。有利地,當作為單劑量投予時,本文所公開的無佐劑組合物可以提供保護性免疫反應。誘導穩健的免疫反應的無明礬組合物尤其可用於約60歲及以上的成人。在實施例中,所述佐劑是水包油乳液,所述水包油乳液由在檸檬酸鹽緩衝液中的角鯊烯作為油相構成,所述油相用表面活性劑聚山梨醇酯80和脫水山梨糖醇三油酸酯穩定。
基於鋁的佐劑
在實施例中,所述佐劑可以是明礬(例如AlPO
4或Al(OH)
3)。通常,所述奈米顆粒基本上結合至明礬。例如,所述奈米顆粒可以是至少80%結合、至少85%結合、至少90%結合或至少95%結合至明礬。通常,在組合物中,所述奈米顆粒是92%至97%結合至明礬。每劑存在的明礬的量通常在約400 µg至約1250 µg之間的範圍內。例如,所述明礬可以以每劑約300 µg至約900 µg、約400 µg至約800 µg、約500 µg至約700 µg、約400 µg至約600 µg或約400 µg至約500 µg的量存在。通常,對於120 µg蛋白奈米顆粒的劑量,明礬以約400 µg存在。
皂苷佐劑
含有皂苷的佐劑也可以與本文所公開的免疫原組合。皂苷是源自皂樹(Quillaja saponaria Molina)樹皮的糖苷。通常,使用多步純化過程製備皂苷,從而產生多種級分。如本文所用,術語“來自皂樹的皂苷級分”一般用於描述皂樹的半純化或確定的皂苷級分或其基本上純的級分。
皂苷級分
用於產生皂苷級分的若干種方法是合適的。級分A、B和C描述於美國專利號6,352,697中,並且可以如下製備。通過層析分離來自Quil A(一種粗水性皂樹提取物)的親脂級分,並且將其用水中的70%乙腈洗脫以回收親脂級分。然後通過半製備型HPLC分離這種親脂級分,使用在酸性水中的從25%至60%乙腈的梯度進行洗脫。在本文中稱為“級分A”或“QH-A”的級分是或對應於在大約39%乙腈下洗脫的級分。在本文中稱為“級分B”或“QH-B”的級分是或對應於在大約47%乙腈下洗脫的級分。在本文中稱為“級分C”或“QH-C”的級分是或對應於在大約49%乙腈下洗脫的級分。關於級分純化的另外資訊可見於美國專利號5,057,540。當如本文所述製備時,皂樹的級分A、B和C各自表示具有可定義特性的化學上緊密相關分子的組或家族。獲得所述級分的層析條件使得就洗脫曲線和生物活性而言批次間重現性是高度一致的。
已經描述了其他皂苷級分。級分B3、B4和B4b描述於EP 0436620中。級分QA1-QA22是描述的EP03632279 B2,Q-VAC(Nor-Feed, AS 丹麥),皂樹(Quillaja saponaria Molina)Spikoside(lsconova AB, Ultunaallén 2B, 756 51 烏普薩拉, 瑞典)。可以使用EP 0 3632 279 B2中的級分QA-1、QA-2、QA-3、QA-4、QA-5、QA-6、QA-7、QA-8、QA-9、QA-10、QA-11、QA-12、QA-13、QA-14、QA-15、QA-16、QA-17、QA-18、QA-19、QA-20、QA-21、和QA-22,尤其是QA-7、QA-17、QA-18、和QA-21。如EP 0 3632 279 B2中(尤其是在第6頁以及在第8頁和第9頁中的實例1中)所述獲得所述級分。
本文所述並用於形成佐劑的皂苷級分通常是基本上純的級分;也就是說,所述級分基本上不存在來自其他材料的污染。在特定方面,基本上純的皂苷級分可以含有按重量計多至40%、按重量計多至30%、按重量計多至25%、按重量計多至20%、按重量計多至15%、按重量計多至10%、按重量計多至7%、按重量計多至5%、按重量計多至2%、按重量計多至1%、按重量計多至0.5%或按重量計多至0.1%的其他化合物,諸如其他皂苷或其他佐劑材料。
ISCOM 結構
皂苷級分可以以稱為ISCOM(免疫刺激複合物)的籠狀顆粒的形式投予。ISCOM可以如EP 0109942B1、EP 0242380B1和EP 0180546 B1中所述製備。在特定實施例中,可以使用轉運和/或乘客抗原,如EP 9600647-3(PCT/SE97/00289)中所述。
基質佐劑
在實施例中,所述ISCOM是ISCOM基質複合物。所述ISCOM基質複合物包含至少一種皂苷級分和脂質。所述脂質至少是固醇,諸如膽固醇。在特定方面,所述ISCOM基質複合物還含有磷脂。所述ISCOM基質複合物還可以含有一種或多種其他免疫調節(佐劑活性)物質,不一定是糖苷,並且可以如EP0436620B1中所述產生,將所述專利通過引用以其整體併入本文。
在其他方面,所述ISCOM是ISCOM複合物。ISCOM複合物含有至少一種皂苷、至少一種脂質和至少一種抗原或表位。所述ISCOM複合物含有通過去污劑處理締合的抗原,使得一部分抗原整合到顆粒中。相比之下,ISCOM基質被配製為與抗原的混合物,並且ISCOM基質顆粒與抗原之間的締合通過靜電和/或疏水相互作用來介導。
根據一個實施例,整合到ISCOM基質複合物或ISCOM複合物中的皂苷級分或也整合到ISCOM或ISCOM基質複合物中或與其混合的至少一種另外的佐劑選自皂樹的級分A、級分B或級分C、皂樹的半純化製劑、皂樹的純化製劑或任何經純化的亞級分(例如,QA 1-21)。
在特定方面,每個ISCOM顆粒可以含有至少兩種皂苷級分。可以使用不同皂苷級分的重量%的任何組合。可以使用任何兩種級分的重量%的任何組合。例如,所述顆粒可以分別含有任何重量%的級分A和任何重量%的另一種皂苷級分,諸如粗皂苷級分或級分C。因此,在特定方面,每個ISCOM基質顆粒或每個ISCOM複合物顆粒可以含有按重量計0.1%至99.9%、按重量計5%至95%、按重量計10%至90%、按重量計15%至85%、按重量計20%至80%、按重量計25%至75%、按重量計30%至70%、按重量計35%至65%、按重量計40%至60%、按重量計45%至55%、按重量計40%至60%或按重量計50%的一種皂苷級分(例如級分A)以及在每種情況下其餘補至100%的另一種皂苷(例如任何粗級分或任何其他級分,例如級分C)。所述重量被計算為皂苷級分的總重量。ISCOM基質複合物和ISCOM複合物佐劑的例子公開於美國公開的申請號2013/0129770中,將所述申請通過引用以其整體併入本文。
在特定實施例中,所述ISCOM基質或ISCOM複合物包含按重量計5%-99%的一種級分(例如級分A)和其餘按重量計補至100%的另一種級分(例如粗皂苷級分或級分C)。所述重量被計算為皂苷級分的總重量。
在另一個實施例中,所述ISCOM基質或ISCOM複合物包含按重量計40%至99%的一種級分(例如級分A)和按重量計1%至60%的另一種級分(例如粗皂苷級分或級分C)。所述重量被計算為皂苷級分的總重量。
在又另一個實施例中,所述ISCOM基質或ISCOM複合物包含按重量計70%至95%的一種級分(例如,級分A)和按重量計30%至5%的另一種級分(例如,粗皂苷級分或級分C)。所述重量被計算為皂苷級分的總重量。在其他實施例中,來自皂樹的皂苷級分選自QA 1-21中的任一種。
除了含有皂苷級分的混合物的顆粒之外,ISCOM基質顆粒和ISCOM複合物顆粒各自都可以僅使用一種皂苷級分形成。本文所公開的組合物可以含有多種顆粒,其中每種顆粒僅含有一種皂苷級分。也就是說,某些組合物可以含有一種或多種不同類型的ISCOM-基質複合物顆粒和/或一種或多種不同類型的ISCOM複合物顆粒,其中每種單獨的顆粒含有來自皂樹的一種皂苷級分,其中一種複合物中的皂苷級分與另一種複合物顆粒中的皂苷級分不同。
在特定方面,一種類型的皂苷級分或粗皂苷級分可以整合到一種ISCOM基質複合物或顆粒中,並且另一種類型的基本上純的皂苷級分或粗皂苷級分可以整合到另一種ISCOM基質複合物或顆粒中。組合物或疫苗可以包含至少兩種類型的複合物或顆粒,每種類型具有一種類型的整合到物理上不同的顆粒中的皂苷。
在所述組合物中,可以使用ISCOM基質複合物顆粒和/或ISCOM複合物顆粒的混合物,其中將一種皂苷級分皂樹和另一種皂苷級分皂樹分開摻入不同的ISCOM基質複合物顆粒和/或ISCOM複合物顆粒中。
各自具有一種皂苷級分的ISCOM基質或ISCOM複合物顆粒可以按重量%的任何組合存在於組合物中。在特定方面,組合物可以含有按重量計0.1%至99.9%、按重量計5%至95%、按重量計10%至90%、按重量計15%至85%、按重量計20%至80%、按重量計25%至75%、按重量計30%至70%、按重量計35%至65%、按重量計40%至60%、按重量計45%至55%、按重量計40至60%或按重量計50%的含有第一皂苷級分的ISCOM基質或複合物,其餘部分由含有不同皂苷級分的ISCOM基質或複合物構成。在多方面中,所述其餘部分是一種或多種ISCOM基質或複合物,其中每種基質或複合物顆粒僅含有一種皂苷級分。在其他方面,所述ISCOM基質或複合物顆粒可以含有多於一種皂苷級分。
在特定組合物中,第一ISCOM基質或ISCOM複合物顆粒中唯一的皂苷級分是級分A,並且第二ISCOM基質或ISCOM複合物顆粒中唯一的皂苷級分是級分C。
優選的組合物包含含有級分A的第一ISCOM基質和含有級分C的第二ISCOM基質,其中級分A ISCOM基質占總皂苷佐劑重量的約70%,並且級分C ISCOM基質占總皂苷佐劑重量的約30%。在另一種優選的組合物中,級分A ISCOM基質占總皂苷佐劑重量的約85%,並且級分C ISCOM基質占總皂苷佐劑重量的約15%。因此,在某些組合物中,級分A ISCOM基質存在的範圍為所述組合物中皂苷佐劑總重量的約70%至約85%,並且級分C ISCOM基質存在的範圍為約15%至約30%。在實施例中,分別地,級分A ISCOM基質占佐劑中級分A ISCOM基質和級分C ISCOM的重量之和的按重量計50%-96%,並且級分C ISCOM基質占剩餘部分。在特別優選的組合物(在本文中稱為MATRIX-M
TM)中,級分A ISCOM基質以所述組合物中皂苷佐劑總重量的約85%存在,並且級分C ISCOM基質以約15%存在。MATRIX-M
TM可以可互換地稱為Matrix-M1。
示例性QS-7和QS-21級分、其生產及其用途描述於美國專利號5,057,540、6,231,859、6,352,697、6,524,584、6,846,489、7,776,343和8,173,141中,這些專利通過引用併入本文。
在實施例中,可以另外或替代地使用其他佐劑。包括在以下文獻中所述的任何佐劑設想在本公開文本的範圍內:Vogel等人, “A Compendium of Vaccine Adjuvants and Excipients (第2版),”(出於所有目的通過引用以其整體併入本文)。其他佐劑包括完全弗氏佐劑(免疫反應的非特異性刺激劑,含有殺死的結核心分枝桿菌(Mycobacterium tuberculosis))、不完全弗氏佐劑和氫氧化鋁佐劑。其他佐劑包括GMCSP、BCG、MDP化合物(諸如thur-MDP和nor-MDP)、CGP(MTP-PE)、脂質A和單磷醯脂質A(MPL)、MF-59、RIBI(其含有從細菌中提取的三種組分)、MPL、海藻糖二黴菌酸酯(TDM)和在2%角鯊烯/TWEEN®聚山梨醇酯80乳劑中的細胞壁骨架(CWS)。在實施例中,所述佐劑可以是少層狀(paucilamellar)脂質囊泡;例如NOVASOMES®。NOVASOMES®是範圍從約100 nm至約500 nm的少層狀非磷脂囊泡。它們包含BRIJ®醇乙氧基化物72、膽固醇、油酸和角鯊烯。已經顯示NOVASOMES®是有效的佐劑(參見美國專利號5,629,021、6,387,373和4,911,928)。
投予和劑量
在實施例中,本公開文本提供了一種用於引發針對一種或多種冠狀病毒和/或流感病毒的免疫反應的方法。在實施例中,所述反應是針對SARS-CoV-2病毒、MERS和SARS中的一種或多種。在實施例中,所述反應是針對異源SARS-CoV-2毒株。異源SARS-CoV-2毒株的非限制性例子包括Cal.20C SARS-CoV-2毒株、P.1 SARS-CoV-2毒株、B.1.351 SARS-CoV-2毒株和B.1.1.7 SARS-CoV-2毒株。所述方法涉及向受試者投予免疫有效量的本文所述的免疫原性組合物。有利地,本文所公開的蛋白質誘導一種或多種特別有用的抗冠狀病毒和/或抗流感反應。
在實施例中,將本文所述的組合物與佐劑一起投予。在實施例中,將本文所述的組合物在沒有佐劑的情況下投予。在多方面中,所述佐劑可以諸如通過非共價相互作用結合至所述奈米顆粒。在其他方面,將所述佐劑與所述奈米顆粒共同投予,但是所述佐劑和奈米顆粒基本上不相互作用。
在實施例中,所述組合物可以用於預防和/或治療SARS-CoV-2感染、異源SARS-CoV-2毒株感染、SARS感染、MERS感染和流感感染或其組合中的一種或多種。因此,本公開文本提供了一種用於引發針對SARS-CoV-2病毒、異源SARS-CoV-2病毒、MERS、SARS和流感病毒中的一種或多種的免疫反應的方法。所述方法涉及向受試者投予免疫有效量的本文所述的組合物。有利地,本文所公開的組合物誘導特別有用的抗冠狀病毒和/或抗流感反應。
在實施例中,本文所述的組合物具有針對SARS-CoV-2病毒或異源SARS-CoV-2毒株的功效,所述功效是在約50%與約99%之間、在約80%與約99%之間、在約75%與約99%之間、在約80%與約95%之間、在約90%與約98%之間、在約75%與約95%之間、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%。在實施例中,本文所述的奈米顆粒或CoV S多肽具有針對Cal.20C SARS-CoV-2毒株的功效,所述功效是在約50%與約99%之間、在約80%與約99%之間、在約75%與約99%之間、在約80%與約95%之間、在約90%與約98%之間、在約75%與約95%之間、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%。在實施例中,本文所述的奈米顆粒或CoV S多肽具有針對P.1 SARS-CoV-2毒株的功效,所述功效是在約50%與約99%之間、在約80%與約99%之間、在約75%與約99%之間、在約80%與約95%之間、在約90%與約98%之間、在約75%與約95%之間、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%。在實施例中,本文所述的奈米顆粒或CoV S多肽具有針對B.1.351 SARS-CoV-2毒株的功效,所述功效是在約50%與約99%之間、在約80%與約99%之間、在約75%與約99%之間、在約80%與約95%之間、在約90%與約98%之間、在約75%與約95%之間、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%。在實施例中,本文所述的奈米顆粒或CoV S多肽具有針對B.1.1.7 SARS-CoV-2毒株的功效,所述功效是在約50%與約99%之間、在約80%與約99%之間、在約75%與約99%之間、在約80%與約95%之間、在約90%與約98%之間、在約75%與約95%之間、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%。
在實施例中,使用HAI測定或通過測量中和抗體來確定本文所述的組合物針對流感病毒的免疫原性。用於進行HAI測定的方法描述于以下文章中,所述文章通過引用以其整體併入本文:Cowling等人 Clin Infect Dis. 2019; 68(10): 1713-1717。在實施例中,可以將所述奈米顆粒流感疫苗的免疫原性與可商購的流感疫苗組合物進行比較。如本文所用,“可商購的流感疫苗組合物”可以是任何可用於醫療用途的流感疫苗組合物。例如,可以將可商購的流感疫苗組合物配製成三價或四價注射劑。在實施例方面中,用於注射的配製品可以包含滅活形式的病毒。在實施例中,可以將可商購的流感疫苗組合物配製用於鼻噴霧劑。在實施例中,用於鼻噴霧劑的配製品可以包含減毒或弱化形式的病毒。在實施例中,本文所公開的組合物誘導結合流感毒株的中和抗體,所述流感毒株相對於相同流感亞型內的病毒中使用的序列已經漂移(即,經歷輕微突變)。在實施例中,所述組合物中使用的毒株中的一種、兩種、三種、四種或全部誘導針對一種漂移毒株、針對兩種漂移毒株、針對三種漂移毒株、針對四種漂移毒株或針對五種漂移毒株的中和抗體。
本文所公開的組合物可以經由全身途徑或粘膜途徑或透皮途徑投予或直接投予到特定組織中。如本文所用,術語“全身投予”包括腸胃外投予途徑。特別地,腸胃外投予包括皮下、腹膜內、靜脈內、動脈內、肌內或胸骨內注射、靜脈內或腎臟透析輸注技術。通常,全身腸胃外投予是肌內注射。如本文所用,術語“粘膜投予”包括口服、鼻內、陰道內、直腸內、氣管內、腸和眼部投予。優選地,投予是肌內的。
可以以單劑量方案或多劑量方案投予組合物。可以在初次免疫方案或在加強免疫方案中使用多劑量。在多劑量方案中,各個劑量可以通過相同或不同的途徑投予,所述途徑例如為腸胃外初次和粘膜加強、粘膜初次和腸胃外加強等。在多個方面中,在先前劑量之後約2週、約3週、約4週、約5週或約6週投予後續加強劑量。在實施例中,在投予先前劑量後3週投予後續加強劑量。在實施例中,第一劑量在第0天投予,並且加強劑量在第21天投予。在實施例中,第一劑量在第0天投予,並且加強劑量在第28天投予。
在實施例中,如以µg測量的劑量可以是包括溶質的劑量的總重量、或奈米顆粒的重量、或奈米顆粒中的蛋白質的重量(例如,血凝素或CoV S多肽的重量)。使用蛋白質濃度測定(A280或ELISA)來測量劑量。
包括用於兒科投予在內的CoV S多肽的劑量可以在約1 µg至約25 µg、約3 µg至約25 µg、約5 µg至約25 µg、約5 µg至約50 µg、約1 µg至約300 µg、約90 µg至約270 µg、約100 µg至約160 µg、約110 µg至約150 µg、約120 µg至約140 µg或約140 µg至約160 µg的範圍內。在實施例中,所述劑量為約120 µg,與明礬一起投予。在多方面中,劑量範圍為從約1 µg至約90 µg。在實施例中,CoV纖突(S)多肽的劑量為約1 µg、約2 µg、約3 µg、約4 µg、約5 µg、約6 µg、約7 µg、約8 µg、約9 µg、約10 µg、約11 µg、約12 µg、約13 µg、約14 µg、約15 µg、約16 µg、約17 µg、約18 µg、約19 µg、約20 µg、約21 µg、約22 µg、約23 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約40 µg、約50 µg、約60 µg、約70 µg、約80 µg、約90 µg、約100 µg、約110 µg、約120 µg、約130 µg、約140 µg、約150 µg、約160 µg、約170 µg、約180 µg、約190 µg、約200 µg、約210 µg、約220 µg、約230 µg、約240 µg、約250 µg、約260 µg、約270 µg、約280 µg、約290 µg或約300 µg,包括在中間的所有值和範圍。在實施例中,CoV S多肽的劑量為約3 µg。在實施例中,CoV S多肽的劑量為約5 µg。在實施例中,CoV S多肽的劑量為約25 µg。在實施例中,CoV S多肽的劑量為約20 µg。
所述免疫原性組合物中血凝素的總量的範圍可以為從約25 µg至約200 µg、約30 µg至約150 µg、約50 µg至約100 µg、約45 µg至約180 µg、約60 µg至約190 µg或約100 µg至約200 µg。在某些實施例中,所述免疫原性組合物中流感HA蛋白的量可以在約5 µg/毒株至約80 µg/毒株、約10 µg/毒株至約75 µg/毒株、約15 µg/毒株至約70 µg/毒株、約20 µg/毒株至約65 µg/毒株、約25 µg/毒株至約60 µg/毒株、約30 µg/毒株至約55 µg/毒株、約35 µg/毒株至約50 µg/毒株、約15 µg/毒株至約60 µg/毒株的範圍內。每毒株的劑量(例如,10 µg/毒株)是指來自特定流感毒株的血凝素的劑量。在實施例中,向受試者投予包含在約5 µg與約100 µg之間的血凝素/毒株的免疫原性組合物。例如,在實施例中,所述組合物包含約5 µg、約6 µg、約7 µg、約7.5 µg、約8 µg、約9 µg、約10 µg、約11 µg、約12 µg、約13 µg、約14 µg、約15 µg、約16 µg、約17 µg、約18 µg、約19 µg、約20 µg、約21、約22、約23、約24、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg、約41 µg、約42 µg、約43 µg、約44 µg、約45 µg、約46 µg、約47 µg、約48 µg、約49 µg、約50 µg、約51 µg、約52 µg、約53 µg、約54 µg、約55 µg、約56 µg、約57 µg、約58 µg、約59 µg、約60 µg、約61 µg、約62 µg、約63 µg、約64 µg、約65 µg、約66 µg、約67 µg、約68 µg、約69 µg、約70 µg、約71 µg、約72 µg、約73 µg、約74 µg、約75 µg、約76 µg、約77 µg、約78 µg、約79 µg、約80 µg、約81 µg、約82 µg、約83 µg、約84 µg、約85 µg、約86 µg、約87 µg、約88 µg、約89 µg、約90 µg、約91 µg、約92 µg、約93 µg、約94 µg、約95 µg、約96 µg、約97 µg、約98 µg、約99 µg或約100 µg的血凝素/毒株。在實施例中,所述組合物包含24 µg至40 µg血凝素/毒株。
在實施例中,向患者投予免疫原性組合物,所述免疫原性組合物含有約5 µg至60 µg血凝素/毒株和約2.5 µg至22.5 µg的CoV S多肽。在實施例中,所述組合物包含約24 µg至40 µg血凝素/毒株和5 µg至約25 µg的CoV S多肽。在實施例中,所述免疫原性組合物含有5 µg、10 µg、35 µg或60 µg血凝素/毒株。在實施例中,所述免疫原性組合物包含2.5 µg、7.5 µg或22.5 µg的CoV S多肽。在實施例中,所述免疫原性組合物含有來自三種或四種流感毒株的血凝素。在實施例中,所述免疫原性組合物含有約40 µg的皂苷佐劑,例如MATRIX-M
TM。在實施例中,所述免疫原性組合物含有約50 µg的皂苷佐劑,例如MATRIX-M
TM。在實施例中,每毒株血凝素的劑量和CoV S多肽的劑量見於表1H。
在實施例中,在初始投予免疫原性組合物後49、50、51、52、53、54、55、56、57、58、59、60或61天,向患者投予加強劑量的免疫原性組合物。在實施例中,在初始投予免疫原性組合物後56天,向患者投予加強劑量的免疫原性組合物。在實施例中,在初始投予免疫原性組合物後56天(+ 5天),向患者投予加強劑量的免疫原性組合物。在實施例中,所述加強劑量含有與初始劑量相同量的血凝素/毒株和CoV S多肽。在實施例中,所述加強劑量含有與初始劑量相比不同量的血凝素/毒株、CoV S多肽或其組合。在實施例中,所述免疫原性組合物的加強劑量中血凝素/毒株的量和CoV S多肽的量選自表1H。
表1H
選擇 | 血凝素 / 毒株 (µg) | CoV S 多肽 (µg) |
A | 60 | 22.5 |
B | 10 | 2.5 |
C | 60 | 22.5 |
D | 10 | 7.5 |
E | 10 | 22.5 |
F | 35 | 7.5 |
G | 5 | 22.5 |
H | 60 | 2.5 |
I | 5 | 7.5 |
J | 5 | 2.5 |
K | 35 | 22.5 |
L | 35 | 2.5 |
M | 60 | 7.5 |
N | 60 | 2.5 |
O | 24 | 25 |
P | 25 | 25 |
Q | 26 | 25 |
R | 27 | 25 |
S | 28 | 25 |
T | 29 | 25 |
U | 30 | 25 |
V | 31 | 25 |
W | 32 | 25 |
X | 33 | 25 |
Y | 34 | 25 |
Z | 35 | 25 |
AA | 36 | 25 |
AB | 37 | 25 |
AC | 38 | 25 |
AD | 39 | 25 |
AE | 40 | 25 |
在實施例中,向患者投予含有約5 µg至60 µg血凝素/毒株的第一免疫原性組合物和含有約2.5 µg至約22.5 µg CoV S多肽的第二免疫原性組合物。在實施例中,所述第一免疫原性組合物含有約5 µg、約10 µg、約35 µg或約60 µg血凝素/毒株。在實施例中,所述第二免疫原性組合物含有約2.5 µg、約7.5 µg、約22.5 µg或約25 µg CoV S多肽。在實施例中,所述第一免疫原性組合物含有來自三種或四種流感毒株的血凝素。在實施例中,所述第一免疫原性組合物中血凝素/毒株的量和所述第二免疫原性組合物中CoV S多肽的量提供於表1H中。在實施例中,第一免疫原性組合物、第二免疫原性組合物或兩者含有約50 µg的皂苷佐劑,例如MATRIX-M
TM。在實施例中,在初始投予第一免疫原性組合物、第二免疫原性組合物或兩者後49、50、51、52、53、54、55、56、57、58、59、60或61天,向患者投予加強劑量的第一免疫原性組合物、第二免疫原性組合物或兩者。在實施例中,在初始投予第一免疫原性組合物、第二免疫原性組合物或兩者後56天,向患者投予加強劑量的免疫原性組合物。在實施例中,在初始投予第一免疫原性組合物、第二免疫原性組合物或兩者後56天(+ 5天),向患者投予加強劑量的免疫原性組合物。在實施例中,所述加強劑量含有與初始劑量相同量的血凝素/毒株和CoV S多肽。在實施例中,所述加強劑量含有與初始劑量相比不同量的血凝素/毒株、CoV S多肽或其組合。在實施例中,第一免疫原性組合物或第二免疫原性組合物的加強劑量中血凝素/毒株的量和CoV S多肽的量選自表1H。可以在有或沒有佐劑的情況下向某些群體投予。在某些方面,組合物可以不含添加的佐劑。在此類情況下,可以將劑量增加約10%。
在實施例中,向患者投予約24 µg至約40 µg血凝素/毒株和大於約20 µg的CoV S多肽劑量。在實施例中,向患者投予24 µg-40 µg血凝素/毒株和約25 µg的CoV S多肽劑量。
在實施例中,所述佐劑的劑量為約1 µg至約100 µg,例如約1 µg、約2 µg、約3 µg、約4 µg、約5 µg、約6 µg、約7 µg、約8 µg、約9 µg、約10 µg、約11 µg、約12 µg、約13 µg、約14 µg、約15 µg、約16 µg、約17 µg、約18 µg、約19 µg、約20 µg、約21 µg、約22 µg、約23 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg、約41 µg、約42 µg、約43 µg、約44 µg、約45 µg、約46 µg、約47 µg、約48 µg、約49 µg、約50 µg、約51 µg、約52 µg、約53 µg、約54 µg、約55 µg、約56 µg、約57 µg、約58 µg、約59 µg、約60 µg、約61 µg、約62 µg、約63 µg、約64 µg、約65 µg、約66 µg、約67 µg、約68 µg、約69 µg、約70 µg、約71 µg、約72 µg、約73 µg、約74 µg、約75 µg、約76 µg、約77 µg、約78 µg、約79 µg、約80 µg、約81 µg、約82 µg、約83 µg、約84 µg、約85 µg、約86 µg、約87 µg、約88 µg、約89 µg、約90 µg、約91 µg、約92 µg、約93 µg、約94 µg、約95 µg、約96 µg、約97 µg、約98 µg、約99 µg或約100 µg的佐劑。在實施例中,佐劑的劑量為約50 µg。在實施例中,所述佐劑是皂苷佐劑,例如MATRIX-M
TM。
在實施例中,投予的劑量的體積為約0.1 mL至約1.5 mL,例如約0.1 mL、約0.2 mL、約0.25 mL、約0.3 mL、約0.4 mL、約0.5 mL、約0.6 mL、約0.7 mL、約0.8 mL、約0.9 mL、約1.0 mL、約1.1 mL、約1.2 mL、約1.3 mL、約1.4 mL或約1.5 mL。在實施例中,投予的劑量的體積為0.25 mL。在實施例中,投予的劑量的體積為0.5 mL。在實施例中,投予的劑量的體積為0.6 mL。
在實施例中,所述劑量可以包含以下濃度的CoV S多肽或血凝素:約1 µg/mL至約50 µg/mL、10 µg/mL至約100 µg/mL、約10 µg/mL至約50 µg/mL、約175 µg/mL至約325 µg/mL、約200 µg/mL至約300 µg/mL、約220 µg/mL至約280 µg/mL或約240 µg/mL至約260 µg/mL。
在實施例中,將本文所述的免疫原性組合物與另外的免疫原性組合物組合投予。在實施例中,所述另外的免疫原性組合物誘導針對SARS-CoV-2的免疫反應。在實施例中,將所述另外的免疫原性組合物在所公開的免疫原性組合物的約1分鐘、約5分鐘、約10分鐘、約20分鐘、約30分鐘、約40分鐘、約50分鐘、約1小時、約2小時、約3小時、約4小時、約5小時、約6小時、約7小時、約8小時、約9小時、約10小時、約11小時、約12小時、約13小時、約14小時、約15小時、約16小時、約17小時、約18小時、約19小時、約20小時、約21小時、約22小時、約23小時、約1天、約2天、約3天、約4天、約5天、約6天、約7天、約8天、約9天、約10天、約11天、約12天、約13天、約14天、約15天、約16天、約17天、約18天、約19天、約20天、約21天、約22天、約23天、約24天、約25天、約26天、約27天、約28天、約29天、約30天或約31天內投予。在實施例中,將所述另外的組合物與第一劑量的本文所述的組合物一起投予。在實施例中,將所述另外的組合物與加強劑量的包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物一起投予。在實施例中,將所述另外的組合物與以下一起投予:(a) 第一免疫原性組合物,其包含 (i) 處於去污劑-核心奈米顆粒形式的CoV S醣蛋白,其中所述去污劑是非離子去污劑,和 (ii) 醫藥上可接受的緩衝液,以及 (b) 第二免疫原性組合物,其包含 (i) 至少三種HA醣蛋白,其中每種HA醣蛋白來自不同的流感毒株,和 (ii) 醫藥上可接受的緩衝液。在實施例中,將所述另外的組合物與初始劑量的第一免疫原性組合物和/或第二免疫原性組合物一起投予。在實施例中,將所述另外的組合物與加強劑量的第一免疫原性組合物和/或第二免疫原性組合物一起投予。
在實施例中,本文提供了一種用於引發針對一種或多種冠狀病毒和/或流感病毒的免疫反應的方法,其包括投予本文所述的免疫原性組合物。在實施例中,本文提供了一種用於引發針對一種或多種冠狀病毒和/或流感病毒的免疫反應的方法,其包括 (a) 投予第一免疫原性組合物,所述第一免疫原性組合物包含 (i) 處於去污劑-核心奈米顆粒形式的CoV S醣蛋白,其中所述去污劑是非離子去污劑,和 (ii) 醫藥上可接受的緩衝液,以及 (b) 投予第二免疫原性組合物,所述第二免疫原性組合物包含 (i) 至少三種醣蛋白HA,其中每種HA醣蛋白來自不同的流感毒株,和 (ii) 醫藥上可接受的緩衝液。在實施例中,將第一免疫原性組合物在第二免疫原性組合物之前約20分鐘、約30分鐘、約40分鐘、約50分鐘、約1小時、約2小時、約3小時、約4小時、約5小時、約6小時、約7小時、約8小時、約9小時、約10小時、約11小時、約12小時、約13小時、約14小時、約15小時、約16小時、約17小時、約18小時、約19小時、約20小時、約21小時、約22小時、約23小時、約1天投予。在實施例中,將第一免疫原性組合物在第二免疫原性組合物之後約20分鐘、約30分鐘、約40分鐘、約50分鐘、約1小時、約2小時、約3小時、約4小時、約5小時、約6小時、約7小時、約8小時、約9小時、約10小時、約11小時、約12小時、約13小時、約14小時、約15小時、約16小時、約17小時、約18小時、約19小時、約20小時、約21小時、約22小時、約23小時、約1天投予。通常,將第一免疫原性組合物和第二免疫原性組合物同時投予(即,彼此在15分鐘內)。在實施例中,將第一免疫原性組合物肌內投予。在實施例中,將第二免疫原性組合物肌內投予。在實施例中,將第二免疫原性組合物鼻內投予。在實施例中,將第一免疫原性組合物肌內投予,並且將第二免疫原性組合物肌內投予。在實施例中,將第一免疫原性組合物肌內投予,並且將第二免疫原性組合物鼻內投予。在實施例中,將第一免疫原性組合物和第二免疫原性組合物肌內投予於同一個臂。在實施例中,將第一免疫原性組合物和第二免疫原性組合物肌內投予於不同的臂。
在實施例中,所述另外的免疫原性組合物包含編碼SARS-CoV-2纖突醣蛋白的mRNA、編碼SARS-CoV-2纖突醣蛋白的質體DNA、編碼SARS-CoV-2纖突醣蛋白的病毒載體或滅活的SARS-CoV-2病毒。
在實施例中,所述另外的免疫原性組合物包含編碼CoV S多肽的mRNA。在實施例中,所述mRNA編碼在SEQ ID NO: 1的位置986和987處包含脯胺酸取代的CoV S多肽。在實施例中,所述mRNA編碼包含完整弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述mRNA編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和完整弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述mRNA編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和無活性的弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述mRNA編碼具有SEQ ID NO: 87的胺基酸序列的CoV S多肽。在實施例中,編碼CoV S多肽的mRNA被封裝在脂質奈米顆粒中。包含編碼CoV S多肽的mRNA的示例性免疫原性組合物描述於Jackson等人 N. Eng. J. Med. 2020.針對SARS-CoV-2的mRNA疫苗的初步報導,其通過引用以其整體併入本文。在實施例中,將包含編碼CoV S多肽的mRNA的組合物以25 µg、100 µg或250 µg的劑量投予。
在實施例中,所述另外的免疫原性組合物包含編碼CoV S多肽的腺病毒載體。在實施例中,所述AAV載體編碼野生型CoV S多肽。在實施例中,所述AAV載體編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和完整弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述AAV載體編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和無活性的弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述AAV載體編碼具有SEQ ID NO: 87的胺基酸序列的CoV S多肽。以下出版物描述了包含編碼CoV S多肽的腺病毒載體的免疫原性組合物,其各自通過引用以其整體併入本文:van Doremalen N.等人 A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques. Science Advances, 2020;van Doremalen N.等人 ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv, (2020)。
在實施例中,所述另外的免疫原性組合物包含去氧核糖核酸(DNA)。在實施例中,所述另外的免疫原性組合物包含質體DNA。在實施例中,所述質體DNA編碼CoV S多肽。在實施例中,所述DNA編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和完整弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述DNA編碼包含在SEQ ID NO: 1的位置986和987處的脯胺酸取代和無活性的弗林蛋白酶切割位點的CoV S多肽。在實施例中,所述DNA編碼具有SEQ ID NO: 87的胺基酸序列的CoV S多肽。
在實施例中,所述另外的免疫原性組合物包含滅活的病毒疫苗。
在實施例中,將包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒和HaSMaN的免疫原性組合物投予於患有或先前已經患有確認的由SARS-CoV-2或異源SARS-CoV-2毒株引起的感染的患者。SARS-CoV-2或異源SARS-CoV-2毒株的感染可以通過核酸擴增測試(例如,聚合酶鏈式反應)或血清學測試(例如,對於針對SARS-CoV-2病毒抗原的抗體的測試)來確認。在實施例中,在患者已被診斷為患有COVID-19後至少約3天、至少約1週、至少約2週、至少約3週、至少約4週,將包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物投予于患者。在實施例中,在患者被診斷患有COVID-19後1週與1年之間,例如約1週、約2週、約3週、約4週、約5週、約6週、約1個月、約2個月、約3個月、約4個月、約5個月、約6個月、約7個月、約8個月、約9個月、約10個月、約11個月或約1年,將包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物投予于患者。在實施例中,在患者被診斷患有COVID-19後1週與20年之間,例如約1週、約2週、約3週、約4週、約5週、約6週、約1個月、約2個月、約3個月、約4個月、約5個月、約6個月、約7個月、約8個月、約9個月、約10個月、約11個月、約1年、約2年、約3年、約4年、約5年、約6年、約7年、約8年、約9年、約10年、約11年、約12年、約13年、約14年、約15年、約16年、約17年、約18年、約19年或約20年,將包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物投予于患者。
在實施例中,在已向患者投予第一免疫原性組合物之後投予包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物。第一免疫原性組合物的非限制性例子包括SARS-CoV-2纖突醣蛋白、編碼SARS-CoV-2纖突醣蛋白的mRNA、編碼SARS-CoV-2纖突醣蛋白的質體DNA、編碼SARS-CoV-2纖突醣蛋白的病毒載體或滅活的SARS-CoV-2病毒。在實施例中,在投予第一免疫原性組合物之後約1週與約1年之間、在約1週與1個月之間、在約3週與4週之間、在約1週與5年之間、在約1年與約5年之間、在約1年與約3年之間、在約3年與約5年之間、在約5年與約10年之間、在約1年與約10年之間或在約1年與約2年之間投予CoV S多肽或包含CoV S多肽的奈米顆粒。在實施例中,在投予第一免疫原性組合物之後約1週與約1年之間,例如在投予第一免疫原性組合物之後約1週、約2週、約3週、約4週、約5週、約6週、約7週、約8週、約9週、約10週、約1個月、約2個月、約3個月、約4個月、約5個月、約6個月、約7個月、約8個月、約9個月、約10個月、約11個月或約1年投予CoV S多肽或包含CoV S多肽的奈米顆粒。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物可用于製備免疫原性組合物以刺激免疫反應,所述免疫反應賦予針對MERS、SARS、SARS-CoV-2和異源SARS-CoV-2毒株中的一種或多種的免疫力或實質免疫力。粘膜免疫力和細胞免疫力兩者都可以有助於針對感染和疾病的免疫力。上呼吸道局部分泌的抗體是抵抗天然感染的主要因子。分泌型免疫球蛋白A(sIgA)參與保護上呼吸道,並且血清IgG參與保護下呼吸道。感染誘導的免疫反應預防相同病毒或抗原性相似的病毒株再感染。用本文所公開的奈米顆粒免疫後在宿主中產生的抗體也可以投予於其他宿主,從而在受試者中提供被動投予。
在實施例中,包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:
(a) NTD的一個或多個胺基酸的缺失,其中所述一個或多個胺基酸選自胺基酸56、57、131、132、144、145、228、229、230、231、234、235、236、237、238、239、240或其組合;以及
(b) NTD的一個或多個胺基酸的突變,其中所述一個或多個突變選自胺基酸5、6、7、13、39、51、53、54、56、57、62、63、67、82、125、129、131、132、133、139、143、144、145、177、200、201、202、209、229、233、240、245或其組合;
(c) RBD的一個或多個胺基酸的突變,其中所述一個或多個突變選自胺基酸333、404、419、426、439、440、464、465、471、477、481、488及其組合;
(d) SD1/2的一個或多個胺基酸的突變,其中所述一個或多個胺基酸選自557、600、601、642、664、668及其組合;
(e) 無活性的弗林蛋白酶切割位點(對應於胺基酸669-672中的一個或多個突變);
(f) S2亞基的一個或多個胺基酸的缺失,其中所述胺基酸選自676-685、676-702、702-711、775-793、806-815及其組合;
(g) S2亞基的一個或多個胺基酸的突變,其中所述胺基酸選自688、703、846、875、937、969、973、974、1014、1058、1105和1163及其組合;
(h) 一個或多個胺基酸從TMCT(胺基酸1201-1260)中的缺失,其中所述CoV S醣蛋白的胺基酸相對於SEQ ID NO: 2編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:胺基酸56的缺失、胺基酸57的缺失、胺基酸131的缺失、N488Y、A557D、D601G、P668H、T703I、S969A、D1105H、N426K和Y440F,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:胺基酸56的缺失、胺基酸57的缺失、胺基酸131的缺失、N488Y、A557D、D601G、P668H、T703I、S969A和D1105H,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:D67A、D202G、L229H、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:胺基酸229-231的缺失、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:胺基酸229-231的缺失、L5F、D67A、D202G、K404N、E471K、N488Y、D601G和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對含有具有選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:L5F、T7N、P13S、D125Y、R177S、K404T、E471K、N488Y、D601G、H642Y、T1014I和V1163F,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對具有包含選自以下的一個或多個修飾的S蛋白的SARS-CoV-2病毒的交叉中和抗體:W139C和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述包含W139C和L439R修飾的CoV S多肽表現為含有具有SEQ ID NO: 117或SEQ ID NO: 5的胺基酸序列的信號肽。在實施例中,所述CoV S蛋白或包含CoV S蛋白的奈米顆粒誘導針對具有選自以下的一個或多個修飾的SARS-CoV-2病毒的交叉中和抗體:D601G、W139C和L439R,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,所述包含D601G、W139C和L439R修飾的CoV S蛋白或奈米顆粒表現為含有具有SEQ ID NO: 117或SEQ ID NO: 5的胺基酸序列的信號肽。
在實施例中,包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對具有選自以下的一個或多個修飾的SARS-CoV-2病毒的交叉中和抗體:D601G、L5F、D67A、D202G、胺基酸229-231的缺失、R233I、K404N、E471K、N488Y和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。在實施例中,包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物誘導針對具有選自以下的一個或多個修飾的SARS-CoV-2病毒的交叉中和抗體:L5F、D67A、D202G、胺基酸229-231的缺失、R233I、K404N、E471K、N488Y和A688V,其中所述胺基酸相對於具有SEQ ID NO: 2的胺基酸序列的CoV S多肽編號。
在實施例中,本文所述的包含CoV S多肽或含有CoV S多肽的奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的組合物具有預防來自SARS-CoV-2病毒或異源SARS-CoV-2毒株(例如,B.1.1.7 SARS-CoV-2毒株、B.1.351 SARS-CoV-2毒株、P.1 SARS-CoV-2毒株、B.1.617.2 SARS-CoV-2毒株、B.1.525 SARS-CoV-2毒株、B.1.526 SARS-CoV-2毒株、B.1.617.1 SARS-CoV-2毒株、a C.37 SARS-CoV-2毒株、B.1.621 SARS-CoV-2毒株、a B.1.1.529 SARS-CoV-2毒株或Cal.20C SARS-CoV-2毒株)的冠狀病毒疾病-19(COVID-19)的功效,在投予最後劑量的本文所述的奈米顆粒或CoV S多肽之後多至約1個月、多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月、多至約12個月、多至約12.5個月、多至約13個月、多至約13.5個月、多至約14個月、多至約14.5個月、多至約15個月、多至約15.5個月、多至約16個月、多至約16.5個月、多至約17個月、多至約17.5個月、多至約18個月、多至約18.5個月、多至約19個月、多至約19.5個月、多至約20個月、多至約20.5個月、多至約21個月、多至約21.5個月、多至約22個月、多至約22.5個月、多至約23個月、多至約23.5個月、多至約24個月、多至約2.1年、多至約2.2年、多至約2.3年、多至約2.4年、多至約2.5年、多至約2.6年、多至約2.7年、多至約2.8年、多至約2.9年、多至約3年或更久時間內,所述功效為約50%至約99%、約80%至約99%、約75%至約99%、約80%至約95%、約90%至約98%、約75%至約95%、約80%至約90%、約85%至約95%、約80%至約95%、至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%、或至少約99%。在實施例中,所述COVID-19是輕度COVID-19。在實施例中,所述COVID-19是中度COVID-19。在實施例中,所述COVID-19是重度COVID-19。在實施例中,所述COVID-19是無症狀的COVID-19。
在實施例中,本公開文本提供了一種產生高親和力抗MERS-CoV、抗SARS-CoV、抗SARS-CoV-2或抗流感病毒抗體中的一種或多種的方法。通過用本文所公開的奈米顆粒免疫而產生的高親和力抗體通過以下方式來產生:向動物投予包含CoV S多肽或奈米顆粒、去污劑-核心奈米顆粒、HaSMaN或其組合的免疫原性組合物,從所述動物中收集血清和/或血漿,以及從所述血清和/或血漿中純化所述抗體。在一個實施例中,所述動物是人。在實施例中,所述動物是雞、小鼠、豚鼠、大鼠、兔、山羊、人、馬、羊或牛。在一個實施例中,所述動物是牛或馬。在另一個實施例中,所述牛或馬動物是轉基因的。在又另一個實施例中,所述轉基因牛或馬動物產生人抗體。在實施例中,所述動物產生單株抗體。在實施例中,所述動物產生多株抗體。在一個實施例中,所述方法還包括投予佐劑或免疫刺激化合物。在另一個實施例中,向人受試者投予經純化的高親和力抗體。在一個實施例中,所述人受試者有感染MERS、SARS、SARS-CoV-2和流感病毒中的一種或多種的風險。
在一些實施例中,本公開文本提供了用於包含奈米顆粒的免疫原性組合物的共配製(即,載藥注射器或預混合)策略。目前使用的典型疫苗投予策略是床邊混合配製品。也就是說,疫苗組合物和佐劑分開儲存,並且在投予前混合。疫苗的預混合、共配製或載藥注射器策略較不常見,歸因於考慮到抗原(例如,血凝素和CoV S多肽)的穩定性及其後續免疫原性能力。本公開文本提供了可以提前預混合和儲存的免疫原性組合物。所公開的疫苗接種策略和配製可以改善疫苗接種的效率,並且可以降低床邊混合失誤的風險,同時保持總體安全性和免疫原性。
可以使用各種容器來儲存和運輸預混合配製品,所述容器包括用於單次投予的注射器和塑膠安瓿。在一些情況下,塑膠安瓿可以使用吹-灌-封製造技術或方法製造。通常,吹-灌-封(BFS)製造方法包括擠出塑膠材料(例如,樹脂)以形成型坯,然後將所述型坯放入模具中並切割成適當尺寸。然後使用填充針或芯棒使塑膠充氣,這又產生了基本上與模具形狀一致的中空安瓿。一旦充氣,就可以將所需體積的液體注入安瓿中,可以將填充針或芯棒移除,並且可以將安瓿密封。因此,BFS可以是無需直接人為干預而可以在無菌環境中發揮性能的自動化過程。
在一些情況下,無菌製造含有所需液體的無菌安瓿的能力可以使BFS製造的安瓿特別適合製藥工業。然而,BFS技術不能與所有的醫藥液體、產品等相容。例如,一些已知的BFS製造方法包括在塑膠仍然相對熱時將液體或產品遞送到安瓿中,這會對溫度敏感的液體和/或產品如疫苗、生物製品等產生不利影響。然而,冷BFS技術的進步增加了合適產品、液體等的種類,允許一些疫苗、生物製品和/或其他溫度敏感藥物容納在BFS安瓿中。
在一些情況下,BFS安瓿可以具有至少部分地基於所需用途和/或經配置的安瓿所容納的所需醫藥液體或劑量的尺寸、形狀和/或配置。例如,一些已知的BFS安瓿可以包括刺穿頂部、擰開頂部、包括陽或陰魯爾連接子的頂部和/或類似物。一些已知的BFS安瓿可以具有基於經配置以安置在其中的液體或劑量的體積的尺寸和/或形狀。此外,一些已知的BFS安瓿可以製造成多個臨時連接的安瓿的條狀物,這可以增加製造、包裝和/或儲存效率和/或類似性能。
在實施例中,本文所述的免疫原性組合物以載藥注射器提供。當在載藥注射器中製備免疫原性組合物時,在投予前將抗原和佐劑組合。在實施例中,所述載藥注射器含有血凝素和CoV S多肽。在實施例中,所述載藥注射器含有血凝素,並且不含CoV S多肽。在實施例中,所述載藥注射器含有CoV S多肽,並且不含血凝素。
在實施例中,從載藥注射器向受試者投予免疫原性組合物。在實施例中,向受試者投予在單個載藥注射器中的含有血凝素和CoV S多肽兩者的免疫原性組合物。在實施例中,從含有CoV S多肽但不含血凝素的載藥注射器向受試者投予免疫原性組合物。在實施例中,從含有血凝素但不含CoV S多肽的載藥注射器向受試者投予免疫原性組合物。
將本公開文本中引用的所有專利、專利申請、參考文獻和期刊文章出於所有目的通過引用以其整體明確地併入本文。
實例 實例 1 冠狀病毒纖突( S )多肽奈米顆粒的表現和純化
已在杆狀病毒表現系統中表現了天然冠狀病毒纖突(S)多肽(SEQ ID NO: 1和SEQ ID NO: 2)和CoV纖突多肽(其具有對應於SEQ ID NO: 3、4、38、41、44、48、51、54、58、61、63、65、67、73、75、78、79、82、83、85、87、106、108、89、112-115、132、133、114、138、141、144、147、151、153、156和158的胺基酸序列),並且挑選並確認了表現冠狀病毒纖突(S)多肽的重組噬斑。在每種情況下,信號肽是SEQ ID NO: 5。
圖 2和
圖 4示出了CoV纖突多肽BV2364、BV2365、BV2366、BV2367、BV2368、BV2369、BV2373、BV2374和BV2375的成功純化。表2示出了上述CoV纖突多肽的序列特徵。
表2:選定的CoV纖突多肽
CoV S 多肽 | 修飾 | SEQ ID NO. |
BV2364 | 缺失的N末端結構域 | 48 |
BV2365 | 無活性的弗林蛋白酶切割位點 | 4 |
BV2361 / BV2366 | 野生型 | 2 |
BV2367 | 胺基酸676-685的缺失、無活性的弗林蛋白酶切割位點 | 63 |
BV2368 | 胺基酸702-711的缺失、無活性的弗林蛋白酶切割位點 | 65 |
BV2369 | 胺基酸806-815的缺失、無活性的弗林蛋白酶切割位點 | 67 |
BV2373,配製成在本文中稱為“NVX-CoV2373”的組合物 | 無活性的弗林蛋白酶切割位點、K973P突變、V974P突變 | 87 |
BV2374 | K973P突變、V974P突變 | 85 |
BV2374 | 無活性的弗林蛋白酶切割位點和His標籤 | 58 |
BV2384 | 無活性的弗林蛋白酶切割位點(GSAS)、K973P、V974P突變 | 110 |
BV2425 | 無活性的弗林蛋白酶切割位點、K973P、V974P突變、胺基酸56的缺失、胺基酸57的缺失、胺基酸131的缺失、N488Y突變、A557D突變、D601G突變、P668H突變、T703I突變、S969A突變和D1105H突變 | 114 |
BV2426 | 無活性的弗林蛋白酶切割位點、K973P突變、V974P突變、D67A突變、D202G突變、L229H突變、K404N突變、E471K突變、N488Y突變、D601G突變和A688V突變 | 115 |
BV2438 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、K404N突變、E471K突變、N488K突變、D67A突變、D202G突變、L229H突變、D601G突變、A688V突變 | 132 |
BV2423 | 無活性的弗林蛋白酶切割位點(GG)、K973P突變、V974P突變、D601G突變 | 133 |
BV2425 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7),K973P突變,V974P突變,胺基酸56、57和131的缺失,N488Y突變,A557D突變,D601G突變,P668H突變,T703I突變,S969A突變,D1105H突變 | 114 |
BV2425-2 | 無活性的弗林蛋白酶切割位點(GG),K973P突變,V974P突變,胺基酸56、57和131的缺失,N488Y突變,A557D突變,D601G突變,P668H突變,T703I突變,S969A突變,D1105H突變 | 138 |
BV2439 | 無活性的弗林蛋白酶切割位點(GG)、K973P突變、V974P突變、K404N突變、E471K突變、N488K突變、D67A突變、D202G突變、L229H突變、D601G突變、A688V突變 | 141 |
BV2441 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、K404N突變、E471K突變、N488Y突變、D67A突變、D202G突變、D601G突變、A688V突變、胺基酸229-231的缺失 | 144 |
BV2442 | 無活性的弗林蛋白酶切割位點(GG)、K973P突變、V974P突變、K404N突變、E471K突變、N488Y突變、D67A突變、D202G突變、D601G突變、A688V突變、胺基酸229-231的缺失 | 147 |
BV2443 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、T7N突變、P13S突變、D125Y突變、R177S突變、K404T突變、E471K突變、N488Y突變、D601G突變、H642Y突變、T1014Y突變、V1163F突變 | 151 |
BV2448 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、W139C突變、S481P突變、D601G突變、L439R突變 | 153 |
BV1.526NY-1 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、T82I突變、D240G突變、E471K突變、D601G突變、A688V突變 | 156 |
BV1.526NY-2 | 無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變、T82I突變、D240G突變、E464K突變、D601G突變、A688V突變 | 158 |
BV2465 | 突變:T6R、G129D、R145G、L439R、T465K、D601G、P668R、D937G、K973P、V974P、無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7) 缺失:143、144 | 164 |
BV2457 | T82I、G129D、E141K、L439R、T471Q、D601G、P668R、Q1058H、K973P、V974P、無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7) | 165 |
BV2472 | 突變:T6R、G129D、R145G、K404N、L439R、T465K、D601G、P668R、D937G、W245I、K973P、V974P、無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7) 缺失:143、144 | 166 |
BV2480 | T82I、Y131S、Y132N、R333K、E471K、N488Y、D601G、P668H、D937N、無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變 | 167 |
BV2481 | T82I、Y131T、Y132S、R333K、E471K、N488Y、D601G、P668H、D937N、無活性的弗林蛋白酶切割位點(QQAQ:SEQ ID NO: 7)、K973P突變、V974P突變 在胺基酸132後天門冬醯胺酸的插入 | 168 |
野生型BV2361蛋白(SEQ ID NO: 2)與人血管緊張素轉換酶2前體(hACE2)結合。進行了生物膜層干涉測量術和ELISA,以評估CoV S多肽的結合。
蛋白質和奈米顆粒產生
通過感染Sf9昆蟲細胞來擴增重組病毒。在約3 MOI(感染複數 = 病毒ffu或pfu/細胞)下用杆狀病毒感染昆蟲細胞培養物。感染後48小時-72小時收穫培養物和上清液。通過在約800 x g下離心15分鐘澄清約30 mL的粗細胞收穫物。如下所述將含有冠狀病毒纖突(S)蛋白的所得粗細胞收穫物純化為奈米顆粒。
為了產生奈米顆粒,將非離子表面活性劑TERGITOL®壬基酚乙氧基化物NP-9用於膜蛋白提取方案中。經由通過陰離子交換層析、小扁豆凝集素親和/HIC和陽離子交換層析進一步純化粗提取物。通過去污劑處理使洗滌過的細胞裂解,然後對其進行低pH處理,這導致BV和Sf9宿主細胞DNA和蛋白質沈澱。使中和的低pH處理裂解液澄清,並且在進行第二次低pH處理之前在陰離子交換和親和層析上進一步純化。
使用親和層析來去除Sf9/BV蛋白、DNA和NP-9,並且濃縮冠狀病毒纖突(S)蛋白。簡言之,小扁豆凝集素是一種含有鈣和錳的金屬蛋白,其可逆地結合含有葡萄糖或甘露糖的多糖和醣基化蛋白。將含冠狀病毒纖突(S)蛋白的陰離子交換流過級分載入到小扁豆凝集素親和層析樹脂(Capto小扁豆凝集素,GE Healthcare)上。醣基化冠狀病毒纖突(S)蛋白選擇性地結合至樹脂,而非醣基化蛋白和DNA在柱流過物中被去除。通過含有高鹽和低摩爾濃度的甲基α-D-吡喃甘露糖苷(MMP)的緩衝液去除弱結合的醣蛋白。
還使用柱洗滌物來將NP-9去污劑用表面活性劑聚山梨醇酯80(PS80)進行去污劑交換。用高濃度的MMP將冠狀病毒纖突(S)多肽以奈米顆粒結構從小扁豆凝集素柱中洗脫。在洗脫後,將冠狀病毒纖突(S)蛋白三聚體組裝成由包含在去污劑核心中的冠狀病毒纖突(S)蛋白三聚體和PS80構成的奈米顆粒。在本實例中描述的方法用於表現和純化本文所述的任何CoV S多肽奈米顆粒。
實例 2 流感病毒去污劑 - 核心奈米顆粒的表現和純化
經由杆狀病毒感染在Sf9細胞中表現來自單一毒株的HA蛋白,並且在收穫前使其生長48小時-96小時。然後通過去污劑提取收集HA蛋白,並且在純化期間將其轉變成去污劑核心奈米顆粒。簡言之,用由25 mM Tris,pH 8.0、1.5 M氯化鈉、0.02% NP9構成的緩衝液預平衡TMAE柱。以≤ 90 cm/hr(24 min停留時間)載入樣品,然後用EQ緩衝液(25 mM Tris(pH 8.0)、50 mM氯化鈉或81 mM氯化鈉(分別對於甲型毒株、乙型毒株)、0.02% NP-9)洗滌。然後使用1.5 CV EQ緩衝液洗脫純化的樣品。
對於甲型毒株,對來自TMAE柱的產物進行奈米過濾,然後施加到用3 CV的由25 mM Tris、50 mM氯化鈉和107 mM氯化鈉(分別對於甲型毒株和乙型毒株)、0.02%(w/v)NP-9(pH 8.0)構成的緩衝液預平衡的小扁豆凝集素親和層析柱上(流速:150 cm/h)。在4 min停留時間下載入樣品。載入後,用3 CV的小扁豆凝集素平衡緩衝液進行洗滌。通過在75 cm/hr和8分鐘停留時間下收集2 CV,用25 mM磷酸鈉(pH 7.5)、200 mM氯化鈉、500 mM甲基-α-D-吡喃甘露糖苷、0.01%(w/v)PS80(pH 7.5)洗脫產物。
對於乙型毒株,將TMAE柱產物使用Capto Blue柱進一步純化。用25 mM Tris,pH 8.0、107 mM氯化鈉、0.02%(w/v)NP-9平衡柱,隨後以225 cm/hr的流速在4分鐘停留時間下載入TMAE產物,並且用2 CV的平衡緩衝液收集。對來自Capto Blue柱的產物進行奈米過濾,然後施加到用3 CV由25 mM Tris、50 mM氯化鈉和107 mM氯化鈉(分別對於甲型毒株和乙型毒株)、0.02%(w/v)NP-9(pH 8.0)構成的緩衝液預平衡的小扁豆凝集素親和層析柱上(流速:150 cm/h)。在4 min停留時間下載入樣品。載入後,用3 CV的小扁豆凝集素平衡緩衝液進行洗滌。通過在75 cm/hr和8分鐘停留時間下收集2 CV,用25 mM磷酸鈉(pH 7.5)、200 mM氯化鈉、500 mM甲基-α-D-吡喃甘露糖苷、0.01%(w/v)PS80(pH 7.5)洗脫產物。
將甲型毒株和乙型毒株兩者的小扁豆凝集素產物濃縮至目標HA濃度,然後將緩衝液交換為最終的原料藥配製緩衝液。通過超濾和滲濾進行濃縮和緩衝液交換。
實例 3 HaSMaN 的配製
將實例2的去污劑-核心奈米顆粒與皂苷佐劑(即,按重量計85%的級分A ISCOM基質和按重量計15%的級分C ISCOM基質)混合,並培育至少24小時。
圖 7(右小圖)示出了HaSMaN的電子顯微術圖像。
實例 4 針對 COVID-19 和流感的組合疫苗的免疫原性和功效
評價了針對COVID-19和流感的組合疫苗(也稱為“qNIV/CoV2373”)的免疫原性和功效。所述組合疫苗包含 (i) 第一疫苗(稱為“CoV2373”),其包含含有CoV S多肽(SEQ ID NO: 87)的奈米顆粒,以及 (ii) 第二疫苗(稱為“qNIV”),其包含含有來自四種不同流感毒株的血凝素(HA)的奈米顆粒。含有甲型流感顆粒的奈米顆粒形成HaSMaN。含有甲型流感病毒顆粒的奈米顆粒形成去污劑-核心奈米顆粒。所述四種不同的流感毒株是:A/堪薩斯州/14/17、A/布里斯班/02/016、B/馬里蘭州/15/16和B/普吉島/3073/13。“標準”組合疫苗含有5 µg CoV S多肽和15 µg HA/毒株。“高劑量”組合疫苗含有5 µg CoV S多肽和60 µg HA/毒株。將奈米顆粒與皂苷佐劑(即,85%級分A ISCOM基質和15%級分C ISCOM基質)預混合。
用標準疫苗或高劑量疫苗對雄性和雌性動物組進行免疫。用含有 (i) 沒有CoV2373的qNIV(每種血凝素以15 µg HA/毒株存在); (ii) 沒有CoV2373的qNIV(每種血凝素以50 µg HA/毒株存在);或 (iii) 沒有qNIV的CoV2373(5 µg CoV S多肽)的疫苗對比較組進行免疫。所有疫苗都含有50 µg皂苷佐劑(
圖 8A)。
將由組合疫苗產生的人ACE2受體抑制抗體水準與僅用qNIV或僅用CoV2373免疫的動物進行比較。用qNIV/CoV2373免疫的動物在單劑量後2週具有輕微升高的hACE2受體阻斷抗體水準(GMT = 34-39),其在加強免疫後2週增加3.2倍-7.3倍(GMT 107-202)。人ACE2抑制力價與用含有5 µg CoV2373的奈米顆粒免疫的動物(GMT = 290)是可比的。單獨用qNIV免疫的動物沒有可測量的hACE抑制抗體(
圖 8B)。在組間比較血凝抑制(HAI)抗體力價。在單劑量後2週,對甲型流感毒株和乙型流感毒株的HAI力價升高,並且在加強免疫後2週加強2倍-7倍。對於所有甲型流感毒株和乙型流感毒株,由qNIV/CoV2373組合產生的HAI力價與通過用低或高劑量qNIV免疫產生的HAI力價是可比的。用5 µg CoV2373疫苗免疫的動物沒有可測量的針對甲型毒株或乙型毒株的HAI抗體(
圖 8C- 圖 8F)。
倉鼠中的免疫原性 qNIV/CoV2373 組合疫苗
我們接著評價在用SARS-CoV-2激發的倉鼠中由qNIV/CoV2373組合疫苗產生的免疫原性和保護作用,與僅含qNIV的疫苗或僅含CoV2373的疫苗相比較。用由10 µg或2.5 µg HA/毒株與5 µg或1 µg CoV2373的組合組成的qNIV/CoV2373對倉鼠組進行免疫。用qNIV(10 µg或2.5 µg HA/毒株)或用CoV2373(5 µg或1 µg)對比較組進行免疫。所有疫苗配製品都輔以15 µg皂苷佐劑。安慰劑組接受配製緩衝液(
圖 9A)。接受qNIV/CoV2373組合的動物在第一次免疫後2週具有升高的抗S-IgG(GMT = 9467-25,295),其在加強免疫後2週增加15倍-30倍(GMT = 275,341-418,124)(
圖 9B、
圖 9C)。在第一劑量的單價CoV2373後2週的抗S IgG力價(GMT = 4576-43,632)和在第二劑量的單價CoV2373後2週的抗S IgG力價(GMT = 302,967-523,143)與接受組合疫苗的動物的那些是可比的(
圖 9B、
圖 9C)。
將qNIV/CoV2373組合引發的人ACE2受體抑制抗體水準與單價CoV2373引發的抗體水準進行比較。用qNIV/CoV2373免疫的倉鼠具有升高的抗體水準(IC
50),其在單劑量後阻斷纖突與hACE2受體結合(GMT = 57-136)。在加強免疫後,受體抑制力價增加6.2倍-16.3倍(GMT = 654-1086)。人ACE2抑制水準與用CoV2373單次免疫後的倉鼠(GMT = 24-230)類似。加強免疫後,人ACE2受體抑制力價增加7.7倍-68倍(GMT = 1636-1769)(
圖 9D、
圖 9E)。
將由qNIV/CoV2373引發的對甲型流感毒株和乙型流感毒株的免疫反應與用qNIV的免疫進行比較。用組合疫苗免疫的倉鼠在單次免疫後對A/堪薩斯州H3N2具有高HAI力價(GMT = 113-202)並且對A/布里斯班H1N1具有高HAI力價(GMT = 143-226)。在加強免疫後A/堪薩斯州H3N2 HAI力價增加6.3倍-14.2倍(GMT = 1280-1810),並且在加強後A/布里斯班H1N1 HAI力價增加5.7倍-10倍(GMT = 1280-1437)。(
圖 10A- 圖 10D)。用qNIV免疫的動物具有與甲型毒株等同的HAI力價。單次免疫後A/堪薩斯州(GMT = 80-106)和A/布里斯班(GMT = 121-211)。在加強免疫後A/堪薩斯州HAI力價增加24倍(GMT = 1940-2560)且A/布里斯班HAI力價增加8倍-12.1倍(GMT 1470-1689)。用組合疫苗免疫的動物在單次免疫後HAI力價升高至B/普吉島(GMT = 80-143),在第二次免疫後HAI力價增加5倍-9倍(GMT = 570-718)。接受qNIV單次免疫的動物在初免/加強免疫後具有可比的B/普吉島HAI力價(GMT = 735-844)(
圖 10E 、圖 10F)。同樣,用qNIV/CoV2373免疫兩次的動物(GMT = 160-142)具有與B/馬里蘭州類似的HAI力價,後者力價等於由用qNIV免疫引發的HAI力價(GMT = 106-242)(
圖 10G、
圖 10H)。
與單獨用qNIV免疫的動物相比,用qNIV/CoV2373免疫的倉鼠組之間病毒中和抗體力價是可比的。用qNIV/CoV2373初免/加強免疫的動物對A/堪薩斯州具有高中和力價(GMT = 15,693-16,916)且對A/布里斯班具有高中和力價(GMT = 6992-10,507)。用qNIV免疫對於A/堪薩斯州(GMT = 13,625-19,314)和A/布里斯班(GMT = 20,146-22,146)引發類似的中和力價(
圖 11A- 圖 11D)。類似地,用qNIV/CoV2373免疫的動物或用qNIV免疫的動物具有可比的乙型毒株中和力價水準(
圖 11E- 圖 11H)。整體而言,這些結果表明qNIV/CoV2373組合疫苗在免疫原性上與qNIV和單價CoV2373比較物等同,表明當qNIV和CoV2373與皂苷佐劑共同投予時,沒有干擾免疫反應。
針對中和 mAb 的競爭性多株 RBD 抗體
在倉鼠中誘導多株抗體,其與原型US-WA纖突RBD中和mAb CR3022、NVX.322.3和NVX.239.12(表3)競爭,而不管是用單價CoV2373還是用組合qNIV進行疫苗接種都如此。當用5 µg單價CoV2373免疫相比1 µg單價CoV2373免疫時,用單價CoV2373免疫的倉鼠具有顯著更高的與US-WA RBD mAb競爭的多株抗體(
圖 12A- 圖 12C)。
表3.SARS-CoV-2纖突單株抗體的功能特徵
抗體 | 同位素 | SARS-CoV-2纖突結合(EC 50,ng/Ml) | SARS-CoV-2纖突RBD a(EC 50,ng/Ml) | ACE2 b受體抑制(IC 50,ng/Ml) | 100% SARS-CoV-2中和(IC 100,ng/Ml) |
NVX.239.12 | IgG1/κ | 7 | 32 | 56 | 12.35 |
NVX.322.03 | IgG1/κ | 28 | 250 | 275 | 185 |
aRBD:受體結合結構域 bACE2:血管緊張素轉換酶2受體 |
qNIV與1 µg或5 µg CoV2373 rS的組合導致針對US-WA RBD測量的競爭性多株抗體水準的一定程度降低。在用單價CoV2373和qNIV/CoV2373組合疫苗免疫的倉鼠中誘導了針對B.1.351變體的競爭性多株抗體反應的類似模式。然而,單價CoV2373或具有qNIV的組合疫苗誘導了與CR3002和NVX.322.3競爭的顯著多株抗體(
圖 12D- 圖 12E)。NVX-239.12不與B.1.351變體RBD結合。
激發後臨床信號
為了評估組合疫苗的保護功效,在用SARS-CoV-2經鼻內途徑進行第二次免疫後21天(研究第35天),經鼻內途徑用SARS-CoV-2激發免疫的倉鼠和安慰劑處理的倉鼠。所有動物在激發後階段存活,直到預定的屍體剖檢(7 dpi)。在激發後的整個時間段內每天監測動物重量。接受安慰劑的動物或用qNIV(2.5 µg或10 µg HA/毒株)免疫的動物至7 dpi損失12.5%至15%的體重。相比之下,用1 µg或5 µg CoV2373免疫的動物保留了它們的重量,在7 dpi體重增加2.6%至5%(
圖 13A)。用qNIV/CoV2373免疫的動物保留了它們的重量,在7 dpi體重增加2.5%至5%,這與未感染的假處理組相同(
圖 13B)。
口腔拭子、支氣管肺泡灌洗液( BAL )和肺樣品中的亞基因組病毒 mRNA
為了檢查qNIV/CoV2373疫苗的功效,使用被設計用於檢測SARS-CoV-2亞基因組(sg)SARS-CoV-2核衣殼(N)RNA的qRT-PCR來確定上呼吸道和下呼吸道中的病毒載量。在感染後2天、4天和7天(dpi)收集口腔拭子。在安慰劑處理的動物的口腔拭子中觀察到最高sgRNA水準,在2 dpi中值峰為4.4(範圍2.7-5.1)log
10RNA拷貝mL
-1。病毒水準在4 dpi保持升至3.2(範圍2.9-4.2)log
10RNA拷貝mL
-1,並且在7 dpi降至3.0 log
10(範圍1.7-3.7)RNA拷貝mL
-1。在來自用10 µg或2.5 µg HA/毒株免疫的動物的口腔拭子中,病毒RNA水準沒有顯著差異,其中sgRNA的最高水準在2 dpi為4.4-4.5(範圍3.9-4.9)log
10RNA拷貝mL
-1,在4 dpi為3.2-3.4(範圍1.7-3.7)log
10RNA拷貝mL
-1,並且在7 dpi為2.5-3.4(1.7-3.9)log
10RNA拷貝mL
-1。來自用5 µg或1 µg CoV2373免疫動物的口腔拭子在2 dpi具有可檢測的病毒RNA(2.9-3.6 log
10拷貝mL
-1)。在4 dpi或7 dpi在用CoV2373免疫的動物的拭子中沒有檢測到病毒RNA(
圖 13C)。僅在用qNIV/CoV2373免疫的動物中在2 dpi收集的拭子中檢測到病毒RNA(3.2-3.5 log
10RNA拷貝mL
-1),而在4 dpi或7 dpi未檢測到複製病毒(
圖 13D)。
在屍體剖檢時獲得BAL洗滌物,並分析病毒RNA。安慰劑組和用10 µg或2.5 µg HA/毒株免疫的組具有最高的病毒RNA中值水準。來自安慰劑組的抽吸物具有中值為5.6(範圍5.1-6.4)log
10sgRNA拷貝mL
-1的複製病毒水準。BAL中的病毒載量在用10 µg HA/毒株免疫的動物中也很高,中值為5.6(範圍4.4-5.9)log
10RNA拷貝mL
-1,並且在用2.5 µg HA/毒株免疫的動物中,中值為5.5(範圍3.6-6.0)log
10RNA拷貝mL
-1。在從用CoV2373(1 µg或5 µg)或用qNIV/CoV2373組合免疫的動物獲得的BAL樣品中幾乎沒有檢測到病毒RNA(
圖 13E)。
在屍體剖檢時收集肺組織,並且評價病毒載量。來自安慰劑處理的動物和接受qNIV的動物的肺勻漿具有最高的病毒載量:安慰劑中值7.1(範圍6.4-8.9)log
10RNA拷貝g
-1;10 µg HA/毒株,7.3(範圍6.7-7.8)log
10RNA拷貝g
-1;和2.5 µg HA/毒株,6.7(範圍6.0-7.7)log
10RNA拷貝g
-1。來自用CoV2373或qNIV/CoV2373組合免疫的動物的肺勻漿幾乎沒有可檢測的病毒(
圖 13F)。
宏觀觀察和微觀觀察:所有動物都存活,直至預定的屍體剖檢(研究第42天)。收集肺並稱重。與用CoV2373或qNIV/CoV2373組合免疫的動物相比,在用安慰劑處理的動物或用qNIV免疫的動物中肺重量顯著更高(p ≤ 0.003)(
圖 13G)。安慰劑處理的動物和qNIV免疫的動物的氣道中的顯微鏡發現是相同的,並且由細支氣管肺泡增生、混合肺泡炎症、伴有周圍組織水腫的血管周圍炎症和罕見的合胞體細胞組成。在用CoV2373或qNIV/CoV2373疫苗免疫的動物的肺中沒有明顯的發現(
圖 14A- 圖 14J)。這些結果與用安慰劑處理的動物和接受qNIV的動物中的高病毒載量和肺炎一致,而接種CoV2373疫苗的動物和接種qNIV/CoV2373疫苗的動物的肺是正常的並且沒有病毒。
成功的組合呼吸道疫苗的另外需要的能力將是面對不可避免的病毒進化時提供覆蓋。RNA呼吸道病毒通常在來自宿主的免疫壓力和來自動物源性來源的抗原轉換下尤其易於快速進化。在南非免疫壓力下SARS-CoV-2病毒的進化已經導致在已經建立了一定水準的群體免疫力的群體中明顯的爆發。在季節性流感的情境下,病毒進化是有效免疫的關鍵挑戰。最近,面對不良實際疫苗有效性的週期性報告,出現了多個重度A(H3N2)主導的流感季。這顯現是由因抗原進化速度快,基於蛋的疫苗產生的抗原錯配和病毒本身而驅動的。
在本研究中,我們證明了qNIV/CoV2373疫苗的組合不僅誘導了針對US-WA的競爭性多株抗體反應,而且誘導了針對SARS-CoV-2纖突蛋白RBD中和表位的B.1.351南非變體的競爭性多株抗體反應。這項研究還證明了對於在US-WA與B.1.352 RBD之間共有的並由CoV2373疫苗誘導的中和表位的潛力。
2019-20的明顯事件顯示了與幾乎沒有季節性流感相伴的新型冠狀病毒和COVID-19疾病的出現和激增。此時,已經提出COVID-19控制措施可能導致季節性流感病例的減少,而其他措施已經提出了生態學機制。在任一情況下,過去的幾個世紀表明流感會重複傳播,並且引起疾病以及高度感染性和臨床上重要的SARS-CoV-2,並且出現的變體可能繼續在全球進化。流感和SAR-CoV-2的共感染已有描述。COVID-19的常見臨床症狀包括發熱、寒戰、咳嗽和呼吸困難,使得難以診斷流感病毒感染。對患有重度疾病的SARS-CoV-2陽性的住院患者的回顧性研究顯示12%(544名患者中的64名)被甲型流感(84%、64名中的54名)和乙型流感(16%、64名中的10名)共感染。然而,流感和SARS-CoV-2共感染的臨床影響是未知的。
由於每年用兩種疫苗免疫的後勤保障,對季節性流感的未來需求和對SARS-CoV-2疫苗的持續需求使得非常期望的組合疫苗具有前景。在這個報告中,我們描述了共配製的流感和SARS-CoV-2奈米顆粒疫苗,其廣泛地對抗共傳播的季節性流感和COVID-19病毒,並且具有由於廣泛保護性反應而解決出現的流感毒株和SARS-CoV-2變體的挑戰的潛力。
材料和方法:病毒儲備物和受體:從疾病控制中心獲得SARS-CoV-2(毒株2019-nCoV/USA-WA1/2020)分離株,並通過在Vero E6細胞中傳代製備病毒儲備物。A/堪薩斯州/14/17、A/布里斯班/02/016、B/馬里蘭州/15/16和B/普吉島/3073/13病毒儲備物由Novavax, Inc.(美國馬里蘭州蓋瑟斯堡市)提供。組胺酸標記的人ACE2受體購自Sino Biologics(中國北京市)。單株抗體CR3022 [23]從Creative BioLabs(美國紐約州雪麗(Shirley),目錄號MRO-1214LC)獲得。SARS-CoV-2 US-WA重組6-組胺酸標記的受體結合結構域(RBD)由Novavax, Inc.(美國馬里蘭州蓋瑟斯堡市)提供。組胺酸標記的B.1.351纖突RBD從Sino Biologics(目錄號40592-V08H85,中國北京市)獲得
NVX-CoV2373 纖突( S )蛋白和重組血凝素疫苗:CoV2373疫苗由全長野生型SARS-CoV-2 S醣蛋白基於GenBank基因序列MN908947核苷酸21563-25384構建。通過突變位於S1/S2切割結構域內的推定弗林蛋白酶切割位點(682-RRAR-685至682-QQAQ-685)來修飾天然全長S蛋白,以賦予蛋白酶抗性。在七肽重複區1(HR1)結構域內的位置K986P和V987P(2P)處插入兩個脯胺酸胺基酸取代,以穩定處於融合前構象的SARS-CoV-2 S。
將合成的轉基因進行密碼子優化並工程化到杆狀病毒載體中,以在草地貪夜蛾(Sf9)昆蟲細胞(GenScript,美國新澤西州皮斯卡塔韋)中表現。用含有TERGITOL NP-9去污劑的Tris緩衝液從質膜經去污劑提取纖突三聚體(命名為CoV2373),並通過離心澄清。使用TMAE陰離子交換和小扁豆凝集素親和層析來純化S-三聚體。將純化的CoV2373在25 mM磷酸鈉(pH 7.2)、300 mM NaCl和0.02%(v/v)聚山梨醇酯中配製。
血凝素( HA )奈米顆粒的選殖和表現:將流感病毒A/堪薩斯州/14/17、A/布里斯班/02/016、B/馬里蘭州/15/16和B/普吉島/3073/13 HA基因進行密碼子優化以在Sf9昆蟲細胞中表現。將合成的經密碼子優化的HA基因選殖到pBac1杆狀病毒轉移載體(Millipore Sigma,美國麻塞諸塞州比爾裡卡)中。將pBac1質體與含有苜蓿銀紋夜蛾多角體病毒基因組的Flash-bacGOLD杆粒(Oxford Expression Technology,英國牛津)轉染至Sf9中。用表現HA基因的重組杆狀病毒感染Sf9細胞培養物。如前所述純化重組HA。
雪貂免疫原性。將雪貂(n = 30,15只雄性和15只雌性)隨機分成5組。用15 µg或60 µg HA/毒株在沒有或混合有5 µg CoV2373的情況下經IM對動物進行免疫。用5 µg CoV2373對比較組進行免疫。所有疫苗都輔以50 µg皂苷佐劑。以間隔21天的初免/加強方案對所有組進行免疫。在初免劑量後21天和加強免疫後14天收集血清用於分析。
倉鼠免疫原性和 SARS-CoV-2 激發。將6-9週齡且重量為約100克的倉鼠(n = 54,27只雄性和27只雌性)隨機分成10組(n = 5-6只/組)。通過肌內(IM)注射用10 µg HA/毒株與5 µg或1 µg CoV2373的組合;2.5 µg HA/毒株與5 µg或1 µg CoV2373的組合;10 µg HA/毒株;2.5 µg HA/毒株;5 µg CoV2373;或1 µg CoV2373對動物進行免疫。在注射當天將疫苗與15 µg皂苷佐劑混合。以間隔14天的初免/加強方案對所有組進行免疫。安慰劑組(n = 5)在第0天和第14天接受配製緩衝液。假處理對照組(n = 5)未免疫。第一次免疫後十四天和加強免疫後14天收集血清用於分析。
SARS-CoV-2 鼻內激發:第二次免疫後三週(研究第35天),對接種疫苗的動物和安慰劑動物用在20 µL無菌磷酸鹽緩衝鹽水(PBS)中的80 mg/kg氯胺酮和5 mg kg-1甲苯噻嗪進行鎮靜,並經鼻內途徑接種2.0 × 10
4pfu的SARS-CoV-2(毒株2019-nCoV/USA-WA1/2020)。
抗纖突 IgG ELISA:使用纖突蛋白ELISA來確定血清中的抗SARS-CoV-2纖突(S)蛋白IgG力價。將微量滴定板(Thermo Fisher Scientific,美國紐約州羅契斯特市)用1.0 µg mL
-1的SARS-CoV-2 S蛋白(CoV2373,批號16Apr20,Novavax, Inc. 美國馬里蘭州蓋瑟斯堡市)包被。將板用PBS-Tween(PBS-T)洗滌,並且用TBS Startblock封閉緩衝液(Thermo Fisher Scientific)阻斷非特異性結合。將血清樣品從1:50稀釋度開始進行3倍連續稀釋,並添加到包被的板中,然後在室溫下培育2小時。培育後,將板用PBS-T洗滌,並且添加辣根過氧化物酶(HRP)-綴合的山羊抗倉鼠IgG(Southern Biotech,美國阿拉巴馬州伯明罕市)保持1小時。將板用PBS-T洗滌,並且添加3,3',5,5'-四甲基聯苯胺(TMB)過氧化物酶底物(Sigma,美國密蘇里州聖路易斯市)。用TMB終止溶液(ScyTek Laboratories, Inc. 猶他州洛根城)終止反應。用SpectraMax Plus板讀取器(Molecular Devices,美國加利福尼亞州桑尼維爾)在OD 450 nm下讀取板。使用SoftMax Pro 6.5.1 GxP軟體通過4-參數擬合來計算EC50值。測定單獨動物抗纖突IgG力價,並且使用GraphPad Prism 8軟體對組幾何平均力價(GMT)和95%置信區間(± 95% CI)作圖。報導了50的低於測定檢測下限(LOD)的力價(起始稀釋度),並且將“25”的值分配給樣品以計算組GMT。
人 ACE2 受體阻斷抗體 ELISA:通過ELISA確定hACE2受體阻斷抗體力價。將微量滴定板用1.0 µg mL
-1SARS-CoV-2 S蛋白(CoV2373,批號02Apr20,Novavax, Inc.,美國馬里蘭州蓋瑟斯堡市)在4ºC下包被過夜。將血清從1:40稀釋開始進行2倍連續稀釋,並且添加到包被的孔中並在室溫下培育1小時。洗滌後,在室溫下向孔中添加30 ng mL
-1的組胺酸標記的hACE2(Sino Biologics,中國北京市)保持1小時。添加HRP綴合的抗組胺酸IgG並培育1小時,然後添加TMB底物。用SpectraMax Plus板讀取器(Molecular Devices,美國加利福尼亞州桑尼維爾)在OD 450 nm下讀取板,並且用SoftMax Pro 6.5.1 GxP軟體分析資料。在SoftMax Pro程式中使用以下等式計算每個樣品的每一稀釋度下的抑制%:100-[(平均值結果/在陽性對照下的對照值)*100]。
生成血清稀釋度相對於抑制%的圖,並且通過對資料的4-參數邏輯(4PL)曲線擬合進行曲線擬合。在SoftMax Pro程式中確定了hACE2針對SARS-CoV-2 rS蛋白的50%抑制下的血清抗體力價(IC50)。使用GraphPad Prism 8軟體對單獨的動物hACE2受體抑制力價(組GMT ± 95% CI)繪圖。對於低於測定檢測下限(LOD)的力價,報導了<40的力價(起始稀釋度),並且將“20”的值分配給樣品以計算組GMT。
生物膜層干涉測量術競爭性結合測定:競爭性結合生物膜層干涉測量術(BLI)測定使用Octet QK 384儀器(FortéBio)進行。BLI研究是用偶聯到Ni-NTA生物感測器尖端的his
6標記的SARS-CoV-2 rS蛋白受體結合結構域(RBD)進行的。所述測定由兩個步驟組成:1) 實驗血清樣品(1:200),免疫前(第0天)陰性對照,和用摻有5 µg mL
-1的纖突特異性單株抗體(mAb)的免疫前血清製備的陽性對照樣品;和2) 將競爭性SARS-CoV-2 mAb(5 µg mL
-1)載入到RBD生物感測器尖端上,並測量另外的結合或競爭。測量血清多株抗體競爭mAb關於結合rS RBD蛋白的競爭。使用Octet資料分析HT10.0軟體分析資料。資料相對於安慰劑第0天血清和rS RBD mAb的結合和競爭的百分比進行歸一化。基於多株抗體競爭的百分比和競爭性mAb的濃度計算血清樣品中的競爭性抗體濃度(µg mL
-1)。
血凝素抑制抗體( HAI ):使用第14天和第28天的血清樣品評價針對流感A/布里斯班/02/2018(H1N1)、A/堪薩斯州/14/17(H3N2)和B毒株(B/馬里蘭州/15/16和B/普吉島/3073/13)的HAI反應。在達爾伯克氏磷酸鹽緩衝鹽水(DPBS)中製備人紅細胞(RBC,Biological Specialty Corporation,美國賓夕法尼亞州亞蘭敦市)的0.75%懸浮液。將血清樣品用來自霍亂弧菌(Denka Seiken,美國德克薩斯州斯坦福市)的受體破壞酶(RDE)在37ºC下處理過夜以消除非特異性紅細胞(RBC)血凝活性。第二天,通過在56ºC下培育1小時使RDE滅活。將RDE處理的血清在96孔U底板中的DPBS(以1:10開始,25 µL)中進行2倍連續稀釋,並與標準流感病毒濃度(4 HA單位,25 µL)一起培育25分鐘。在培育結束時,向每個孔中添加0.75%的人RBC懸浮液(50 µL),並將板在室溫下培育45分鐘。通過觀察樣品孔和陰性對照孔中由RBC形成的O-環形狀確定血凝抑制(HAI)。HAI力價被記錄為觀察到HAI(最後一個孔具有O-環)的最高血清稀釋度的倒數。對於低於測定檢測限(LOD)的力價,報導了< 10的力價(起始稀釋度),並且將值“5”分配給樣品以計算組幾何平均力價(GMT)。
微量中和( MN )測定:使用第14天和第28天的血清樣品,評價針對流感A/堪薩斯州/14/17(H3N2)、A/布里斯班/02/208 H1N、B/普吉島/3073/13和B/馬里蘭州/15/2016的病毒中和抗體。將血清樣品在56ºC下熱滅活30分鐘,進行2倍連續稀釋(以1:20開始,50 µL)並與100 TCID50病毒(50 µL)一起培育2小時。在培育結束時,將100 µL的1.5 x 10
5mL
-1MDCK細胞添加到每個孔中,並且將板用5% CO
2培育,對於甲型流感病毒在37ºC下培育,或者對於乙型流感病毒在32ºC下培育。在培育18小時-22小時後,用80%冷丙酮固定細胞,並與鼠單株抗甲型流感或乙型流感核蛋白(Millipore Billerica,美國麻塞諸塞州)一起培育,然後與過氧化物酶綴合的山羊抗小鼠IgG(Kirkegaard and Perry Laboratories,美國馬里蘭州蓋瑟斯堡市)一起培育。使用用3-胺基-9-乙基咔唑(AEC)底物(Sigma Aldrich,美國密蘇里州聖路易斯市)顯色後的光密度計算每種血清樣品的50%微量中和力價(50% MN)。對於低於測定檢測限(LOD)的力價,報導了< 20的力價(起始稀釋度),並且將值“10”分配給樣品以計算組幾何平均力價(GMT)。
口腔拭子、支氣管肺泡灌洗液( BAL )和肺組織樣品收集:在研究第37天、第39天和第42天(2、4和7 dpi)收集口腔拭子。在7 dpi進行屍體剖檢時收集BAL樣品和肺。將肺稱重,分成兩半;將一組稱重(約0.1至0.2克)並快速冷凍用於病毒力價測定。將第二組保存在福馬林中用於組織病理學分析。對於病毒載量測定,將組織稱重,置於預標記的Sarstedt冷凍管(2/樣品)中,並在乾冰上快速冷凍。使用掌上型組織勻漿器(Omni International,美國佐治亞州肯尼索市)在0.5 mL RNA-Stat中製備肺勻漿約20秒。通過離心澄清樣品,並且分離上清液用於病毒載量測定。
通過 qRT-PCR 定量亞基因組( sg ) RNA:qRT-PCR測定利用被設計用於擴增並結合至冠狀病毒的核衣殼(N)基因的保守區的引物和探針。將信號與標準曲線進行比較,並計算得出拷貝數/mL。對於qRT-PCR測定,用與氯仿混合的RNA-STAT 60(Tel-Test “B”)從肺勻漿中提取病毒RNA,將其沈澱並懸浮於無RNA酶的0.04% NaN
3(AVE)緩衝液(Qiagen目錄號1020953)中。為了產生擴增反應的對照,使用相同的程式從病毒儲備物中分離RNA。通過將病毒RNA的量與質體對照的已知量進行比較來確定病毒RNA的量。將每3 µL 10
8個拷貝的最終稀釋液分成10 µL的單次使用等分試樣,在-80ºC下儲存。用2.5 mL含有Taq-聚合酶的2X緩衝液製備主混合物,所述緩衝液由TaqMan RT-PCR套組(Bioline #BIO-78005)製備。從套組中添加50 µL RT和100 µL RNA酶抑制劑。以1.5 mL的體積添加2 µM濃度的引物對。添加0.5 mL水和350 µL濃度為2 µM的探針,並且渦旋試管。對於反應,將45 µL主混合物和5 µL樣品RNA一式三份地添加到96孔板的孔中。
對於對照曲線製作,製備對照病毒RNA,使其每3 µL含有10
6至10
7個拷貝。使用無RNA酶的水,通過將5 µL對照添加到45 µL水中,並重複此操作進行7次稀釋,製備對照RNA的十倍連續稀釋液。標準曲線範圍為1至10
7個拷貝/反應。對於其曲線,sg-N使用已知質體。如上所述製備每種稀釋液的一式兩份樣品。為了擴增,將板置於Applied Biosystems 7500序列檢測器(ThermoFisher Scientific)中,並且使用以下程式擴增:48ºC下持續30分鐘,95ºC下持續10分鐘,然後是95ºC下持續15秒和55ºC下持續1分鐘循環40次。通過從標準曲線外推並乘以0.2 mL提取體積的倒數計算每mL中RNA的拷貝數。對於鼻洗滌物,每mL為50至5 x 10
8個RNA拷貝的範圍。以每克勻漿的RNA拷貝數報導肺病毒載量。此研究中使用的引物和探針的序列如下:
2019-nCoV_N1-F: 5’-GAC CCC AAA ATC AGC GAA AT-3’ (SEQ ID NO: 169)
2019-nCoV_N1-R: 5’-TCT GGT TAC TGC CAG TTG AAT CTG-3’ (SEQ ID NO: 170)
2019-nCoV_N1-P: 5’-6-FAM/ACCCCGCAT/ZEN/TACGTTTGGTGGACC/3IABkFQ (SEQ ID NO: 171)
Sg-N-F 5’-CGATCTCTTGTAGATCTGTTCTC-3’ (SEQ ID NO: 172)
Sg-N-R 5’-GGTGAACCAAGACGCAGTAT-3’ (SEQ ID NO: 173)
Sg-N-P 5’-6-FAM/TAACCAGAA/ZEN/TGGAGAACGCAGTGGG/3IABkFQ (SEQ ID NO: 174)
組織病理學:將激發後7天屍體剖檢時收集的肺樣品置於10%中性福馬林中。處理固定的組織,並用蘇木精和伊紅(H&E)染色用於組織學檢查。專業執照病理學家(Experimental Pathology Laboratories, Inc.(EPI,美國維吉尼亞州斯特林市)以盲化方式檢查H&E載玻片。
統計分析:使用GraphPad Prism 9.0.0軟體進行統計分析。圖示顯示出單獨動物的血清抗體力價,並且繪製幾何平均力價(GMT)和95%置信區間(95% CI)區間。對病毒載量以中值、四分位距以及最小值和最大值繪圖。使用學生t檢定來確定如圖例所示的配對組之間的差異。p ≤ 0.05被認為是顯著的。
實例 5 評價免疫原性組合物的安全性及其針對 COVID-19 和流感的功效的 1/2 期研究
在含有約640名年齡為50-70歲的健康參與者的1/2期試驗中評價了組合免疫原性組合物針對COVID-19和流感的免疫原性和功效,所述組合免疫原性組合物也稱為“qNIV/CoV2373”或“ICC疫苗”。參與者的年齡中值為59歲。試驗群體含有62%男性和38%女性。100%的參與者先前接受過具有編碼CoV S多肽的mRNA的初次COVID-19接種系列或包含編碼CoV S多肽的DNA的腺病毒疫苗。
所述組合免疫原性組合物包含 (i) 含有來自四種不同流感毒株的血凝素(HA)的奈米顆粒;(ii) 含有SEQ ID NO: 87的CoV S多肽的奈米顆粒;和 (iii) 皂苷佐劑(即,85%級分A ISCOM基質和15%級分C ISCOM基質)。評價了CoV S多肽和HA的14種不同組合劑量(表4)。表4示出了試驗的研究設計和每組中血凝素、CoV S多肽和皂苷佐劑的量。在第0天向患者投予初始劑量的免疫原性組合物,並且在投予初始劑量後56(+5天)投予加強劑量的免疫原性組合物。
將組合免疫原性組合物針對COVID-19和流感的免疫原性和功效與含有血凝素奈米顆粒和皂苷佐劑的免疫原性組合物(血凝素免疫原性組合物)和含有CoV S多肽和皂苷佐劑的免疫原性組合物(CoV S多肽免疫原性組合物)進行比較。
表4:研究設計
疫苗組 | N | 第0天 | 第56天(+ 5天) | |||||
血凝素的量/毒株(µg) | CoV S多肽的量(µg) | 皂苷佐劑(µg) | 血凝素的量/毒株(µg) | CoV S多肽的量(µg) | 皂苷佐劑(µg) | |||
ICC 疫苗配製品 | ||||||||
A | 40 | 60 | 22.5 | 50 | 60 | 22.5 | 50 | |
B | 40 | 10 | 2.5 | 50 | 10 | 2.5 | 50 | |
C | 40 | 60 | 22.5 | 50 | 60 | 22.5 | 50 | |
D | 40 | 10 | 7.5 | 50 | 10 | 7.5 | 50 | |
E | 40 | 10 | 22.5 | 50 | 10 | 22.5 | 50 | |
F | 40 | 35 | 7.5 | 50 | 35 | 7.5 | 50 | |
G | 40 | 5 | 22.5 | 50 | 5 | 22.5 | 50 | |
H | 40 | 60 | 2.5 | 50 | 60 | 2.5 | 50 | |
I | 40 | 5 | 7.5 | 50 | 5 | 7.5 | 50 | |
J | 40 | 5 | 2.5 | 50 | 5 | 2.5 | 50 | |
K | 40 | 35 | 22.5 | 50 | 35 | 22.5 | 50 | |
L | 40 | 35 | 2.5 | 50 | 35 | 2.5 | 50 | |
M | 40 | 60 | 7.5 | 50 | 60 | 7.5 | 50 | |
N | 40 | 60 | 2.5 | 50 | 60 | 2.5 | 50 | |
血凝素免疫原性組合物 | ||||||||
O 1 | 40 | 60 | 0 | 75 | 0 | 5 | 50 | |
CoV S 多肽免疫原性組合物 | ||||||||
P | 40 | 0 | 5 | 50 | 0 | 5 | 50 | |
總計 | 640 | |||||||
組合疫苗耐受良好。最常見的誘發的局部不良事件是注射部位的疼痛和壓痛。最常見的全身性不良事件是疲勞、頭痛、不適、肌肉疼痛或發熱。大多數不良事件是0級、1級或2級不良事件。存在罕見的3級事件,並且沒有4級事件。不良事件按CoV S多肽的劑量基本沒有變化。然而,不良事件隨著血凝素劑量的增加而輕微增加。沒有特別關注的不良事件。
在第0天、第28天、第56天和第70天收集患者的血清,以定量抗纖突IgG抗體的力價和針對各種流感毒株的血凝素抑制抗體(HAI)幾何平均力價。
圖 15示出了從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的抗纖突IgG抗體的力價。
圖 16示出了從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對A/布里斯班H1N1的HAI幾何平均力價。
圖 17示出了從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對A/堪薩斯州H3N2的HAI幾何平均力價。
圖 18示出了從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對B/馬里蘭州(Vic)的HAI幾何平均力價。
圖 19示出了從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對B/普吉島(Yam)的HAI幾何平均力價。
此資料顯示,含有血凝素和CoV S多肽的組合的組合物與含有單獨CoV S多肽的組合物相比誘導可比的或更多的抗纖突IgG抗體。(圖15)另外,所述組合物有效對抗四種流感病毒株。
本公開文本的編號實施例1. 一種免疫原性組合物,其包含:
(a) 處於去污劑-核心奈米顆粒形式的冠狀病毒S(CoV S)醣蛋白,其中所述去污劑是非離子去污劑;
(b) 至少三種血凝素(HA)醣蛋白,其中每種HA醣蛋白來自不同的流感毒株;以及
(c) 醫藥上可接受的緩衝液。
2. 根據實施例1所述的免疫原性組合物,其中所述至少三種HA醣蛋白處於選自以下的形式:
(a) 包含血凝素(HA)的去污劑-核心奈米顆粒;
(b) HaSMaN(血凝素皂苷基質奈米顆粒);
(c) 滅活的全流感病毒;
(d) 從流感病毒提取的血凝素組合物;任選地流感裂解病毒粒子組合物或亞單位流感病毒組合物;
以及它們的任何組合。
3. 根據實施例1-2中任一項所述的免疫原性組合物,其中至少一種HA醣蛋白處於包含HA的去污劑-核心奈米顆粒的形式,並且至少一種HA醣蛋白處於HaSMaN的形式。
4. 根據實施例1-3中任一項所述的免疫原性組合物,其中所述至少三種HA醣蛋白產生自基於細胞培養的方法或基於蛋的製造方法。
5. 根據實施例2-4中任一項所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒的血凝素醣蛋白來自乙型流感毒株。
6. 根據實施例2-5中任一項所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒的血凝素醣蛋白來自甲型流感毒株。
7. 根據實施例2-6中任一項所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒是胰蛋白酶抗性奈米顆粒。
8. 根據實施例2-7中任一項所述的免疫原性組合物,其中所述HaSMaN是胰蛋白酶抗性奈米顆粒。
9. 根據實施例1-9中任一項所述的免疫原性組合物,其中所述去污劑是PS80。
10. 根據實施例1-9中任一項所述的免疫原性組合物,其中所述流感毒株是選自H1、H2、H3、H4、H5、H6、H7、H8、H9、H10、H11、H12、H13、H14、H15、H16、H17和H18的亞型的毒株。
11. 根據實施例2-10中任一項所述的免疫原性組合物,其中所述醫藥上可接受的緩衝液包含 (i) 約25 mM的磷酸鈉;(ii) 約150 mM的氯化鈉;(iii) 約100 mM的鹽酸精胺酸;(iv) 約5%的海藻糖;其中所述組合物的pH為約7.5。
12. 根據實施例2-11中任一項所述的免疫原性組合物,其包含另外的一種或多種去污劑-核心奈米顆粒和另外的一種或多種HaSMaN,其中每種去污劑-核心奈米顆粒包含乙型毒株HA醣蛋白,並且每種HaSMaN包含甲型毒株HA醣蛋白,其中每種HA醣蛋白來自不同的流感毒株。
13. 根據實施例1-12中任一項所述的免疫原性組合物,其中所述CoV S醣蛋白包含:
(i) 具有滅活的弗林蛋白酶切割位點的S1亞基,其中所述S1亞基包含N末端結構域(NTD)、受體結合結構域(RBD)、亞結構域1和亞結構域2(SD1/2),其中所述滅活的弗林蛋白酶切割位點具有QQAQ的胺基酸序列(SEQ ID NO: 7);
其中所述NTD任選地包含選自以下的一個或多個修飾:
(a) 選自胺基酸56、57、131、132、144、145、228、229、230、231、234、235、236、237、238、239、240及其組合的一個或多個胺基酸的缺失;
(b) 在胺基酸132後1、2、3或4個胺基酸的插入;以及
(c) 選自胺基酸5、6、7、13、51、53、56、57、62、63、67、82、125、129、131、132、133、139、143、144、145、177、200、201、202、209、229、233、240、245及其組合的一個或多個胺基酸的突變;
其中所述RBD任選地包含選自胺基酸333、404、419、426、439、440、464、465、471、477、481、488及其組合的一個或多個胺基酸的突變;
其中所述SD1/2結構域任選地包含選自557、600、601、642、664、668及其組合的一個或多個胺基酸的突變;以及
(ii) S2亞基,其中胺基酸973和974是脯胺酸,
其中所述S2亞基任選地包含選自以下的一個或多個修飾:
(a) 一個或多個胺基酸從676-685、676-702、702-711、775-793、806-815及其組合的缺失;
(b) 選自688、703、846、875、937、969、1014、1058、1105和1163及其組合的一個或多個胺基酸的突變;以及
(c) 自TMCT的一個或多個胺基酸的缺失;
其中所述CoV S醣蛋白的胺基酸相對於具有SEQ ID NO: 2的序列的多肽編號。
14. 根據實施例14所述的免疫原性組合物,其中所述CoV S多肽包含與SEQ ID NO: 86-89、105、106、112-115和164-168中的任一個具有至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性的胺基酸序列或由所述胺基酸序列組成。
15. 根據實施例14所述的免疫原性組合物,其中
所述S2亞基、NTD、RBD和SD1/2中的每一個與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基或結構域至少95%相同。
16. 根據實施例14所述的免疫原性組合物,其中
所述S2亞基、NTD、RBD和SD1/2中的每一個與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基或結構域至少97%相同。
17. 根據實施例14所述的免疫原性組合物,其中
所述S2亞基、NTD、RBD和SD1/2中的每一個與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基或結構域至少99%相同。
18. 根據實施例14所述的免疫原性組合物,其中
所述S2亞基、NTD、RBD和SD1/2中的每一個與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基或結構域至少99.5%相同。
19. 根據實施例1-18中任一項所述的免疫原性組合物,其包含三種或四種血凝素醣蛋白。
20. 根據實施例1-19中任一項所述的免疫原性組合物,其包含多至4種、多至5種、多至6種、多至7種、多至8種、多至9種或多至10種HA醣蛋白。
21. 根據實施例1-20中任一項所述的免疫原性組合物,其中每種HA醣蛋白處於奈米顆粒的形式。
22. 根據實施例21所述的免疫原性組合物,其中每個奈米顆粒包含來自單一流感毒株的HA醣蛋白。
23. 根據實施例22所述的免疫原性組合物,其中每個奈米顆粒是去污劑-核心奈米顆粒或HaSMaN。
24. 根據實施例14所述的免疫原性組合物,其中所述S2亞基與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同。
25. 根據實施例14所述的免疫原性組合物,其中
所述NTD與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同。
26. 根據實施例14所述的免疫原性組合物,其中
所述RBD與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同。
27. 根據實施例14所述的免疫原性組合物,其中
所述SD1/2與具有SEQ ID NO: 2的胺基酸序列的CoV S醣蛋白的對應亞基至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同。
28. 根據實施例1-27中任一項所述的免疫原性組合物,其包含佐劑。
29. 根據實施例28所述的免疫原性組合物,其中所述佐劑包含至少兩種iscom顆粒,其中:
第一iscom顆粒包含皂樹的級分A,且不包含皂樹的級分C;並且
第二iscom顆粒包含皂樹的級分C,且不包含皂樹的級分A。
30. 根據實施例29所述的免疫原性組合物,其中皂樹的級分A和皂樹的級分C分別占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計約92%和按重量計約8%。
31. 根據實施例29所述的免疫原性組合物,其中皂樹的級分A和皂樹的級分C分別占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計約85%和按重量計約15%。
32. 根據實施例28所述的免疫原性組合物,其中將所述佐劑以約50 µg或約75 µg的劑量投予。
33. 一種在受試者中刺激針對SARS-CoV-2、異源SARS-CoV-2毒株、流感病毒或其組合的免疫反應的方法,其包括投予根據實施例1-32中任一項所述的免疫原性組合物。
34. 根據實施例33所述的方法,其中向所述受試者在第0天投予第一劑量,並且在第56天投予加強劑量。
35. 根據實施例33所述的方法,其中向所述受試者投予約1 µg至約25 µg的CoV S醣蛋白。
36. 根據實施例33所述的方法,其中向所述受試者投予約3 µg、約5 µg、約25 µg、約22.5 µg、約7.5 µg或約2.5 µg的冠狀病毒S醣蛋白。
37. 根據實施例33所述的方法,其中向所述受試者投予約5 µg、約10 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg或約60 µg的血凝素/毒株。
38. 根據實施例33-37中任一項所述的方法,其包括向所述受試者投予約20 µg至約50 µg的CoV S醣蛋白和約24 µg至約40 µg的血凝素/毒株。
39. 根據實施例33-37中任一項所述的方法,其包括向所述受試者投予約1 µg至約50 µg的CoV S醣蛋白和約5 µg至約60 µg的血凝素/毒株。
40. 根據實施例33-37中任一項所述的方法,其包括向所述受試者投予約3 µg、約5 µg、約25 µg、約22.5 µg、約7.5 µg或約2.5 µg的冠狀病毒S醣蛋白。
41. 根據實施例33-37中任一項所述的方法,其包括向所述受試者投予約5 µg、約10 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg或約60 µg的血凝素/毒株。
42. 根據實施例33所述的方法,其包括將所述免疫原性組合物肌內投予。
43. 根據實施例33和35-42中任一項所述的方法,其中投予單劑量的所述免疫原性組合物。
44. 根據實施例33-43中任一項所述的方法,其中所述異源SARS-CoV-2毒株選自Cal.20C SARS-CoV-2毒株、P.1 SARS-CoV-2毒株、B.1.351 SARS-CoV-2毒株、B.1.1.7 SARS-CoV-2毒株、SARS-CoV-2 B.1.617.2毒株、B.1.525毒株、B.1.526毒株、B.1.617.1毒株、C.37毒株、B.1.621毒株或SARS-CoV-2 ο毒株。
45. 根據實施例33-43中任一項所述的方法,其中所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是至少50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%或約100%。
46. 根據實施例33-43中任一項所述的方法,其中所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是約50%至約99%、約50%至約95%、約50%至約90%、約50%至約85%、約50%至約80%、約60%至約99%、約60%至約95%、約60%至約90%、約60%至約85%、約60%至約80%、約40%至約99%、約40%至約95%、約40%至約90%、約40%至約85%、約40%至約80%、約40%至約75%、約40%至約70%、約40%至約65%、約40%至約55%或約40%至約50%。
47. 一種用於在受試者中刺激針對SARS-CoV-2、異源SARS-CoV-2毒株、流感病毒或其組合的免疫反應的方法,其包括:
(a) 投予第一免疫原性組合物,所述第一免疫原性組合物包含 (i) 處於去污劑-核心奈米顆粒形式的CoV S醣蛋白,其中所述去污劑是非離子去污劑,和 (ii) 醫藥上可接受的緩衝液;以及
(b) 投予第二免疫原性組合物,所述第二免疫原性組合物包含 (i) 至少三種醣蛋白HA,其中每種HA醣蛋白來自不同的流感毒株,和 (ii) 醫藥上可接受的緩衝液。
48. 根據實施例47所述的方法,其中所述第一免疫原性組合物的劑量包含約1 µg至約50 µg的CoV S醣蛋白。
49. 根據實施例47-48中任一項所述的方法,其中所述第二免疫原性組合物的劑量包含在約5 µg與約100 µg之間的血凝素。
50. 根據實施例47-49中任一項所述的方法,其中將所述第一免疫原性組合物和所述第二免疫原性組合物肌內投予。
51. 根據實施例47-49中任一項所述的方法,其中將所述第一免疫原性組合物肌內投予且將所述第二免疫原性組合物鼻內投予。
52. 根據實施例47-451中任一項所述的方法,其中將所述第一免疫原性組合物和所述第二免疫原性組合物彼此在15分鐘內投予。
53. 根據實施例47-50和52中任一項所述的方法,其中將所述第一免疫原性組合物和所述第二免疫原性組合物投予於同一個臂。
54. 根據實施例47-50和52中任一項所述的方法,其中將所述第一免疫原性組合物和所述第二免疫原性組合物投予於不同的臂。
55. 根據實施例47-54中任一項所述的方法,其中所述第二免疫原性組合物包含至少三種HA醣蛋白,其中每種醣蛋白獨立地處於選自以下的形式:
(a) 包含血凝素(HA)的去污劑-核心奈米顆粒;
(b) HaSMaN(血凝素皂苷基質奈米顆粒);
(c) 滅活的全流感病毒;
(d) 從流感病毒提取的血凝素組合物;任選地流感裂解病毒粒子組合物或亞單位流感病毒組合物;
以及它們的任何組合。
56. 根據實施例55所述的方法,其中至少一種HA醣蛋白處於包含HA的去污劑-核心奈米顆粒的形式,並且至少一種HA醣蛋白處於HaSMaN的形式。
57. 根據實施例47-56中任一項所述的方法,其中所述第二免疫原性組合物包含至少三種處於從病毒提取的血凝素組合物形式的HA醣蛋白。
58. 根據實施例57所述的方法,其中所述從病毒提取的血凝素組合物是流感裂解病毒粒子。
59. 根據實施例55所述的方法,其中所述第二免疫原性組合物包含至少一種處於包含血凝素的去污劑-核心奈米顆粒形式的HA醣蛋白和至少一種處於HaSMaN形式的血凝素。
60. 根據實施例47-59中任一項所述的方法,其中所述第二免疫原性組合物包含至少四種HA醣蛋白,其中每種HA醣蛋白來自不同的流感毒株。
61. 一種載藥注射器,其包含根據實施例1-32中任一項所述的免疫原性組合物。
通過引用併入
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圖 1示出了SARS-CoV-2纖突(S)蛋白的野生型胺基酸序列(SEQ ID NO: 1)的示意圖。弗林蛋白酶切割位點RRAR(SEQ ID NO: 6)以粗體突出顯示,並且信號肽加底線。
圖 2示出了CoV S多肽BV2364、BV2365、BV2366、BV2367、BV2368、BV2369、BV2373、BV2374和BV2375的純化。資料揭示具有含有QQAQ的胺基酸序列(SEQ ID NO: 7)的無活性弗林蛋白酶切割位點的BV2365(SEQ ID NO: 4)和BV2373(SEQ ID NO: 87)被表現為單鏈(S0)。相比之下,含有完整弗林蛋白酶切割位點的CoV S多肽(例如BV2364、BV2366和BV2374)被切割,如通過切割產物S2的存在所證實的。
圖 3示出了BV2373 CoV S多肽的一級結構和對弗林蛋白酶切割位點的修飾K986P和V987P。
圖 4示出了野生型CoV S多肽以及CoV S多肽BV2365和BV2373的純化。
圖 5示出了冠狀病毒纖突(S)蛋白(SEQ ID NO: 86)(BV2373)的示意圖。弗林蛋白酶切割位點QQAQ(SEQ ID NO: 7)加單底線,並且K986P和V987P突變加雙底線。
圖 6A示出了含有信號肽的野生型SARS-CoV-2 S多肽的一級結構,其相對於SEQ ID NO: 1編號。
圖 6B示出了沒有信號肽的野生型SARS-CoV-2 S多肽的一級結構,其相對於SEQ ID NO: 2編號。
圖 7示出了單獨的流感HA去污劑核心奈米顆粒(左)、單獨的皂苷佐劑(中)(即85%級分A ISCOM基質和15%級分C ISCOM基質)以及HA奈米顆粒和皂苷佐劑的組合(其形成血凝素皂苷基質奈米顆粒(HaSMaN)(右)的透射電子顯微術(TEM)圖像的例子。
圖 8A- 圖 8F示出了用qNIV/CoV2373組合疫苗免疫的雪貂對SARS-CoV-2纖突醣蛋白和流感血凝素的免疫反應。(
圖 8A)雄性和雌性雪貂組(n = 6只/組)用15 µg或60 µg血凝素(HA)/毒株與5 µg CoV2373及50 µg皂苷佐劑的組合免疫。比較組用15 µg或60 µg HA/毒株免疫或用5 µg CoV22373及50 µg皂苷佐劑免疫。以間隔21天的兩劑量對所有組進行免疫。紅色三角指示血清收集天。(
圖 8B)人血管緊張素轉換酶-2(hACE2)受體阻斷抗體力價。1劑量後21天和加強免疫後14天(研究第35天)的血凝素抑制抗體(HAI)力價。(
圖 8C)A/堪薩斯州/14/2017。(
圖 8D)A/布里斯班/02/2018。(
圖 8E)B/普吉島/3070/2013。(
圖 8F)B/馬里蘭州/15/2016。棒指示幾何平均力價(GMT),並且誤差棒指示95%置信區間。
圖 9A- 圖 9E示出了用qNIV/CoV2373組合疫苗免疫的倉鼠對SARS-CoV-2纖突醣蛋白和受體阻斷抗體的免疫反應。(
圖 9A)雄性和雌性倉鼠組(n = 5-6只/組)用2.5 µg或10 µg血凝素(HA)/毒株與1 µg或5 µg CoV2373及15 µg皂苷佐劑的組合免疫。比較組用2.5 µg或10 µg HA/毒株或者1 µg或5 µg CoV2373及15 µg皂苷佐劑免疫。通過肌內途徑(IM)以間隔14天的2劑量對動物進行免疫。安慰劑組接受配製緩衝液。收集血清用於分析,如紅色三角形所指示的。在第二次免疫後21天,通過鼻內(IN)途徑用2.0 x 10
4pfu的SARS-CoV-2感染免疫的動物和安慰劑動物。在感染後2天、4天和7天(dpi,藍色三角形)收集口腔拭子。在7 dpi收集支氣管肺泡灌洗液和肺樣品(黑色三角形)。(
圖 9B,
圖 9C)分別為1劑量後14天和加強免疫後14天(研究第28天)的抗纖突IgG力價。(
圖 9D,
圖 9E)分別為1劑量後14天和加強免疫後14天的人ACE-2(hACE2)受體阻斷抗體力價。棒指示組幾何平均力價(GMT),並且誤差棒指示95%置信區間(95% CI)。單獨動物值用彩色符號指示。水準黑色虛線指示檢測限(LOD)。
圖 10A- 圖 10H示出了用qNIV/CoV2373組合疫苗免疫的倉鼠對流感HA的免疫反應。如
圖 8A中所指示,用qNIV/CoV2373疫苗的組合或用組分疫苗免疫倉鼠組。在一劑量後14天和加強免疫後14天(研究第28天)分析血清的血凝素抑制抗體(HAI)力價。(
圖 10A,
圖 10B)A/堪薩斯州/14/2017。(
圖 10C,
圖 10D)A/布里斯班/02/2018。(
圖 10E,
圖 10F)B/普吉島/3070/2013。(
圖 10G,
圖 10H)B/馬里蘭州/15/2016。棒指示幾何平均力價,並且誤差棒指示95%置信區間。
圖 11A- 圖 11H示出了用qNIV/CoV2373組合疫苗免疫的倉鼠中的流感病毒中和抗體。如
圖 8A中所指示,用組合qNIV/CoV2373或用組分疫苗免疫倉鼠組。在1劑量後14天和加強免疫後14天(研究第28天)測定回應於A/堪薩斯州/14/2017(
圖 11A,
圖 11B)、A/布里斯班/02/2018(
圖 11C,
圖 11D)、B/普吉島/3073/2013(
圖 11E,
圖 11F)以及B/馬里蘭州/15/2016(
圖 11G,
圖 11H)的病毒中和力價。棒指示幾何平均力價(GMT),並且誤差棒指示95%置信區間。水準虛線指示檢測限(LOD)。
圖 12A- 圖 12E示出了組合qNIV/CoV2373疫苗引發了通過生物膜層干涉測量術(BLI)測定為結合SARS-CoV-2的受體結合結構域(RBD)中高度保守的隱蔽表位的抗體。通過BLI通過免疫血清與受體位點特異性中和單株抗體的競爭性抗體結合,確定了由qNIV/CoV2373組合或單價CoV2373引發的抗體的特異性。水準棒指示組幾何平均值,並且誤差棒指示95%置信區間。彩色符號指示單獨動物值。
圖 12A- 圖 12C示出了針對SARS-CoV-2 US-WA RBD的抗體。
圖 12D- 圖 12E示出了針對SARS-CoV-2 B.1.351南非RBD的抗體。
圖 13A- 圖 13G示出了用qNIV/CoV2373組合疫苗免疫的倉鼠的體重變化和對於SARS-CoV-2引起的上呼吸道和下呼吸道感染的預防。用間隔14天的qNIV/CoV2373或組分疫苗的初免/加強方案免疫雄性和雌性倉鼠組(n = 5-6只/組)。第二次免疫後三週(研究第35天),通過鼻內途徑用2.0 x 10
4pfu激發動物。
圖 13A- 圖 13B示出了直至感染後7天(dpi)的體重變化(SARS-CoV-2激發後的變化百分比)。資料是接種疫苗組、安慰劑組和假處理組的平均值± SEM。
圖 13C- 圖 13D示出了在感染後2天、4天和7天(dpi)採集頰粘膜拭子中的亞基因組(sg)RNA。通過qRT-PCR分析sgRNA。
圖 13E示出了在感染後7天(dpi)收集的支氣管肺泡灌洗液中的sgRNA病毒載量。
圖 13F示出了在7 dpi收集的肺勻漿中的sgRNA病毒載量。在盒須圖中,中值由水平線指示,盒的頂部和底部指示四分位距,並且須線指示每個實驗組的最小值和最大值(n = 5-6只/組)。單獨動物值用彩色符號指示。虛線指示測定檢測限(LOD)。使用學生t檢定(配對,雙尾)來確定在2 dpi、4 dpi和7 dpi在安慰劑處理的動物與免疫的動物之間病毒sgRNA水準的顯著差異。不顯著(ns),***p ≤ 0.001,****p ≤ 0.0001。
圖 13G示出了在7 dpi從接種疫苗的動物、安慰劑處理的動物和未處理的假處理動物收集的肺的重量。棒指示平均值,並且誤差棒指示±標準差(SD)。單獨動物值用彩色符號指示。使用學生t檢定(配對,雙尾)來確定所指示的配對組之間的肺重量的顯著差異。
圖 14A- 圖 14J示出了用qNIV/CoV2373組合疫苗免疫並用SARS-CoV-2激發的倉鼠的肺中的組織病理學變化。用具有2.5 µg或10 µg血凝素(HA)/毒株與1 µg或5 µg CoV2373(輔以皂苷佐劑)的組合qNIV/CoV2373免疫雄性和雌性倉鼠組。用2.5 µg或10 µg HA/毒株或用1 µg或5 µg CoV2373重組纖突(輔以15 µg皂苷佐劑)對比較組進行免疫。以間隔14天的2劑量對所有組進行免疫。安慰劑組接受配製緩衝液。第二次免疫後三週(研究第35天),所有動物鼻內接受2.0 x 10
4pfu SARS-CoV-2激發,並且在7 dpi收集肺。組織學圖像用蘇木精和伊紅(H&E)染色。
圖 14A是示出正常肺的假處理對照圖像。
圖 14B示出了安慰劑處理的動物的肺中的顯微鏡發現,顯示氣道通過伴有混合肺泡炎症的細支氣管-肺泡增生(箭號)而發生實變。單核炎症細胞圍繞血管(箭頭),水腫使周圍組織擴張(箭頭)。
圖 14C- 圖 14D示出了用qNIV免疫的動物的肺中的顯微鏡發現,顯示組織學變化類似於安慰劑組,包括伴有具有血管周圍炎症的混合肺泡炎症的廣泛細支氣管-肺泡增生(箭號)和擴張的血管壁(箭頭)。
圖 14E- 圖 14F示出了來自用單價CoV2373免疫的動物的肺的圖像,沒有顯示出顯著的顯微鏡發現。
圖 14G- 圖 14J是來自用qNIV/CoV2373組合疫苗免疫的動物的肺的圖像,沒有顯示出顯著的顯微鏡發現。放大10倍。
圖 15示出了根據實例5從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的抗纖突IgG抗體的力價。
圖 16示出了根據實例5從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對A/布里斯班 H1N1的HAI幾何平均力價。
圖 17示出了根據實例5從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對A/堪薩斯州 H3N2的HAI幾何平均力價。
圖 18示出了根據實例5從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對B/馬里蘭州(Vic)的HAI幾何平均力價。
圖 19示出了根據實例5從免疫後第0天至第28天,隨血凝素和CoV S多肽的劑量而變的針對B/普吉島(Yam)的HAI幾何平均力價。
序列表 <![CDATA[<110> Novavax, Inc.]]> Patel, Nita Zhou, Bin Guebre-Xabier, Mimi Tian, Jing-Hui Portnoff, Alyse Massare, Michael Shinde, Vivek Fries, Louis Smith, Gale <![CDATA[<120> 冠狀病毒和流感病毒組合物及其使用方法]]> <![CDATA[<130> NOVV-093/01WO 305047-2996]]> <![CDATA[<150> US 63/332,537]]> <![CDATA[<151> 2022-04-19]]> <![CDATA[<150> US 63/255,685]]> <![CDATA[<151> 2021-10-14]]> <![CDATA[<150> U]]>S 63/193,356 <![CDATA[<151> 2021-05-26]]> <![CDATA[<150> US 63/184,727]]> <![CDATA[<151> 2021-05-05]]> <![CDATA[<160> 174 ]]> <![CDATA[<170> PatentIn 3.5版]]> <![CDATA[<210> 1]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 1]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 2]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 3]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組S蛋白]]> <![CDATA[<400> 3]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 4]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組S蛋白]]> <![CDATA[<400> 4]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 5]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 信號肽]]> <![CDATA[<400> 5]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser 1 5 10 <![CDATA[<210> 6]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 6]]> Arg Arg Ala Arg 1 <![CDATA[<210> 7]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 7]]> Gln Gln Ala Gln 1 <![CDATA[<210> 8]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 8]]> Gln Arg Ala Arg 1 <![CDATA[<210> 9]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 9]]> Arg Gln Ala Arg 1 <![CDATA[<210> 10]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 10]]> Arg Arg Ala Gln 1 <![CDATA[<210> 11]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 11]]> Gln Gln Ala Arg 1 <![CDATA[<210> 12]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 12]]> Arg Gln Ala Gln 1 <![CDATA[<210> 13]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 13]]> Gln Arg Ala Gln 1 <![CDATA[<210> 14]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 14]]> Asn Asn Ala Asn 1 <![CDATA[<210> 15]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 15]]> Asn Arg Ala Arg 1 <![CDATA[<210> 16]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 16]]> Arg Asn Ala Arg 1 <![CDATA[<210> 17]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 17]]> Arg Arg Ala Asn 1 <![CDATA[<210> 18]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 18]]> Asn Asn Ala Arg 1 <![CDATA[<210> 19]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 19]]> Arg Asn Ala Asn 1 <![CDATA[<210> 20]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 20]]> Asn Arg Ala Asn 1 <![CDATA[<210> 21]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 21]]> Ala Ala Ala Ala 1 <![CDATA[<210> 22]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 22]]> Ala Arg Ala Arg 1 <![CDATA[<210> 23]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 23]]> Arg Ala Ala Arg 1 <![CDATA[<210> 24]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 24]]> Arg Arg Ala Ala 1 <![CDATA[<210> 25]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 25]]> Ala Ala Ala Arg 1 <![CDATA[<210> 26]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 26]]> Arg Ala Ala Ala 1 <![CDATA[<210> 27]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 27]]> Ala Arg Ala Ala 1 <![CDATA[<210> 28]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 28]]> Gly Gly Ala Gly 1 <![CDATA[<210> 29]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 29]]> Gly Arg Ala Arg 1 <![CDATA[<210> 30]]> <![CDATA[<211> 4]]> <![CDATA[<212]]>> PRT]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> 重組弗林蛋白酶切割位點]]> <br/> <br/><![CDATA[<400> 30]]> <br/> <br/><![CDATA[Arg Gly Ala Arg 1 <![CDATA[<210> 31]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 31]]> Arg Arg Ala Gly 1 <![CDATA[<210> 32]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 32]]> Gly Gly Ala Arg 1 <![CDATA[<210> 33]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 33]]> Arg Gly Ala Gly 1 <![CDATA[<210> 34]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 34]]> Gly Arg Ala Gly 1 <![CDATA[<210> 35]]> <![CDATA[<211> 3819]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 35]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacgcaggg ctcgctctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctt ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tctgaacccg tcctgaaggg cgtgaagctg cactacacc 3819 <![CDATA[<210> ]]> 36 <![CDATA[<211> 1279]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 36]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr His His His His His 1265 1270 1275 His <![CDATA[<210> 37]]> <![CDATA[<211> 3837]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 37]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacgcaggg ctcgctctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctt ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tctgaacccg tcctgaaggg cgtgaagctg cactacaccc accaccacca ccaccac 3837 <![CDATA[<210> 38]]> <![CDATA[<211> 1266]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 38]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr His His His 1250 1255 1260 His His His 1265 <![CDATA[<210> 39]]> <![CDATA[<211> 60]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 39]]> Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met 1 5 10 15 Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys 20 25 30 Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 35 40 45 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 50 55 60 <![CDATA[<210> 40]]> <![CDATA[<211> 1213]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突]]>蛋白 <![CDATA[<400> 40]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1205 1210 <![CDATA[<210> 41]]> <![CDATA[<211> 1200]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 41]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 <![CDATA[<210> 42]]> <![CDATA[<211> 1219]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 42]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His His His 1205 1210 1215 His <![CDATA[<210> 43]]> <![CDATA[<211> 3657]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 43]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacgcaggg ctcgctctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctc accaccacca ccaccac 3657 <![CDATA[<210> 44]]> <![CDATA[<211> 1219]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 44]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His His His 1205 1210 1215 His <![CDATA[<210> 45]]> <![CDATA[<211> 318]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 45]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 305 310 315 <![CDATA[<210> 46]]> <![CDATA[<211> 955]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 46]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Ile Thr Asn 1 5 10 15 Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val 20 25 30 Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser 35 40 45 Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val 50 55 60 Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp 65 70 75 80 Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln 85 90 95 Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr 100 105 110 Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly 115 120 125 Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys 130 135 140 Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr 145 150 155 160 Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser 165 170 175 Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val 180 185 190 Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly 195 200 205 Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn 210 215 220 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys 225 230 235 240 Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp 245 250 255 Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys 260 265 270 Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn 275 280 285 Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val 290 295 300 Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr 305 310 315 320 Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu 325 330 335 His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 340 345 350 Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser 355 360 365 Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu 370 375 380 Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe 385 390 395 400 Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr 405 410 415 Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser 420 425 430 Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala 435 440 445 Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe 450 455 460 Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly 465 470 475 480 Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys 485 490 495 Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp 500 505 510 Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala 515 520 525 Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro 530 535 540 Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu 545 550 555 560 Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu 565 570 575 Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly 580 585 590 Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln 595 600 605 Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala 610 615 620 Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala 625 630 635 640 Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser 645 650 655 Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu 660 665 670 Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr 675 680 685 Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 690 695 700 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 705 710 715 720 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 725 730 735 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 740 745 750 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 755 760 765 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp 770 775 780 Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp 785 790 795 800 Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn 805 810 815 Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu 820 825 830 Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 835 840 845 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 850 855 860 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 865 870 875 880 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp 885 890 895 Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val 900 905 910 Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 915 920 925 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu 930 935 940 Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 945 950 955 <![CDATA[<210> 47]]> <![CDATA[<211> 2868]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 47]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagca tcactaacct gtgccccttc 60 ggagaggtct tcaacgccac ccgcttcgct tccgtgtacg cctggaacag gaagagaatc 120 tcaaactgcg tcgctgacta ctccgtgctg tacaactcag cctccttcag caccttcaag 180 tgctacggcg tgtcaccaac taagctgaac gacctgtgct tcaccaacgt ctacgccgac 240 tccttcgtga tcaggggaga cgaggtcaga cagatcgctc ctggccagac tggaaagatc 300 gccgactaca actacaagct gcccgacgac ttcaccggtt gcgtcatcgc ttggaacagc 360 aacaacctgg actctaaagt gggtggcaac tacaactacc tgtaccgcct gttccgtaag 420 tcaaacctga agccattcga gagggacatc agcactgaaa tctaccaggc cggatctacc 480 ccttgcaacg gtgtcgaggg cttcaactgc tacttccccc tgcagtccta cggtttccag 540 ccaactaacg gtgtgggcta ccagccttac agagtggtcg tgctgagctt cgaactgctc 600 cacgctcctg ctactgtgtg cggtccaaag aagtctacca acctggtcaa gaacaagtgc 660 gtgaacttca acttcaacgg cctgaccgga actggtgtcc tgaccgagag caacaagaag 720 ttcctgccct tccagcagtt cggaagggac atcgctgaca ccactgacgc tgtgcgcgac 780 cctcagaccc tggaaatcct ggacatcact ccatgctcat tcggaggtgt ctccgtgatc 840 acccctggca ccaacacttc taaccaggtc gctgtgctgt accaggacgt caactgcacc 900 gaggtccctg tggccatcca cgctgaccag ctgaccccca cttggcgcgt gtactccacc 960 ggcagcaacg tgttccagac tcgtgctggt tgcctgatcg gcgccgagca cgtgaacaac 1020 agctacgaat gcgacatccc catcggcgct ggaatctgcg cctcttacca gacccagact 1080 aacagcccac gcagggctcg ctctgtggcc tctcagtcaa tcatcgctta caccatgtca 1140 ctgggcgctg aaaactccgt ggcctactct aacaactcaa tcgccatccc caccaacttc 1200 actatcagcg tgaccactga gatcctgcca gtcagcatga ccaagacttc tgtggactgc 1260 actatgtaca tctgcggaga cagcaccgaa tgctctaacc tgctgctgca gtacggctct 1320 ttctgcaccc agctgaaccg tgctctgact ggaatcgccg tggagcagga caagaacact 1380 caggaagtct tcgctcaggt gaagcaaatc tacaagaccc cacctatcaa ggacttcggc 1440 ggattcaact tctcccagat cctgcctgac ccctccaagc caagcaagcg ctctttcatc 1500 gaggacctgc tgttcaacaa ggtcactctg gccgacgctg gattcatcaa gcagtacgga 1560 gactgcctgg gtgacatcgc cgctcgtgac ctgatctgcg ctcagaagtt caacggtctg 1620 accgtgctgc ccccactgct gactgacgaa atgatcgccc agtacactag cgccctgctg 1680 gctggaacca tcacttctgg ttggaccttc ggtgctggcg ccgctctgca gatccctttc 1740 gctatgcaga tggcctaccg tttcaacgga atcggtgtca cccagaacgt gctgtacgag 1800 aaccagaagc tgatcgctaa ccagttcaac tcagccatcg gaaagatcca ggacagcctg 1860 agctctactg cctctgctct gggcaagctg caggacgtcg tgaaccagaa cgcccaggct 1920 ctgaacaccc tggtcaagca gctgtcatcc aacttcggtg ctatcagctc tgtgctgaac 1980 gacatcctgt cccgcctgga caaggtcgag gccgaagtgc agatcgaccg cctgatcact 2040 ggccgtctgc agtcactgca gacctacgtg actcagcagc tgatcagggc cgctgaaatc 2100 agagcctccg ctaacctggc cgctaccaag atgagcgagt gcgtcctggg tcaatctaag 2160 cgtgtggact tctgcggcaa gggataccac ctgatgtcat tccctcagtc tgctccccac 2220 ggtgtggtgt tcctgcacgt cacctacgtg ccagcccagg agaagaactt caccactgcc 2280 cctgctatct gccacgacgg caaggctcac ttccccaggg aaggtgtctt cgtgagcaac 2340 ggcacccact ggttcgtcac tcagagaaac ttctacgagc cacagatcat caccactgac 2400 aacactttcg tgtctggaaa ctgcgacgtg gtcatcggta tcgtcaacaa caccgtgtac 2460 gaccccctgc agccagagct ggactcattc aaggaggaac tggacaagta cttcaagaac 2520 cacacctccc ctgacgtcga cctgggcgac atctcaggaa tcaacgcttc cgtcgtgaac 2580 atccagaagg agatcgaccg cctgaacgaa gtggccaaga acctgaacga aagcctgatc 2640 gacctgcagg agctgggcaa gtacgaacag tacatcaagt ggccttggta catctggctg 2700 ggtttcatcg ctggcctcat cgctatcgtg atggtgacca tcatgctgtg ctgcatgact 2760 tcatgctgct cctgcctgaa gggctgctgc agctgcggat cttgctgcaa gttcgacgag 2820 gacgactctg aacccgtcct gaagggcgtg aagctgcact acacctaa 2868 <![CDATA[<210> 48]]> <![CDATA[<211> 942]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 48]]> Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 1 5 10 15 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 20 25 30 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 35 40 45 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 50 55 60 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 65 70 75 80 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 85 90 95 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 100 105 110 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 115 120 125 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 130 135 140 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 145 150 155 160 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 165 170 175 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 180 185 190 Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val 195 200 205 Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser 210 215 220 Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp 225 230 235 240 Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile 245 250 255 Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn 260 265 270 Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu 275 280 285 Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val 290 295 300 Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile 305 310 315 320 Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly 325 330 335 Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg 340 345 350 Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu 355 360 365 Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro 370 375 380 Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met 385 390 395 400 Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr 405 410 415 Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu 420 425 430 Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln 435 440 445 Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys 450 455 460 Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys 465 470 475 480 Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr 485 490 495 Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp 500 505 510 Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr 515 520 525 Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser 530 535 540 Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly 545 550 555 560 Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn 565 570 575 Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile 580 585 590 Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser 595 600 605 Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn 610 615 620 Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly 625 630 635 640 Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val 645 650 655 Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser 660 665 670 Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 675 680 685 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly 690 695 700 Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 705 710 715 720 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 725 730 735 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 740 745 750 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 755 760 765 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 770 775 780 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 785 790 795 800 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser 805 810 815 Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp 820 825 830 Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile 835 840 845 Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu 850 855 860 Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 865 870 875 880 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile 885 890 895 Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 900 905 910 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp 915 920 925 Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 930 935 940 <![CDATA[<210> 49]]> <![CDATA[<211> 960]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 49]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Ile Thr Asn 1 5 10 15 Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val 20 25 30 Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser 35 40 45 Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val 50 55 60 Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp 65 70 75 80 Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln 85 90 95 Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr 100 105 110 Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly 115 120 125 Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys 130 135 140 Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr 145 150 155 160 Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser 165 170 175 Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val 180 185 190 Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly 195 200 205 Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn 210 215 220 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys 225 230 235 240 Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp 245 250 255 Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys 260 265 270 Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn 275 280 285 Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val 290 295 300 Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr 305 310 315 320 Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu 325 330 335 His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 340 345 350 Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser 355 360 365 Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu 370 375 380 Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe 385 390 395 400 Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr 405 410 415 Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser 420 425 430 Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala 435 440 445 Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe 450 455 460 Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly 465 470 475 480 Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys 485 490 495 Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp 500 505 510 Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala 515 520 525 Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro 530 535 540 Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu 545 550 555 560 Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu 565 570 575 Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly 580 585 590 Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln 595 600 605 Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala 610 615 620 Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala 625 630 635 640 Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser 645 650 655 Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu 660 665 670 Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr 675 680 685 Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 690 695 700 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 705 710 715 720 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 725 730 735 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 740 745 750 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 755 760 765 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp 770 775 780 Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp 785 790 795 800 Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn 805 810 815 Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu 820 825 830 Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 835 840 845 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 850 855 860 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 865 870 875 880 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp 885 890 895 Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val 900 905 910 Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 915 920 925 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu 930 935 940 Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr His His His His His 945 950 955 960 <![CDATA[<21]]>0> 50]]> <br/><![CDATA[<211> 2883]]> <br/><![CDATA[<212> DNA]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> 重組纖突蛋白]]> <br/> <br/><![CDATA[<400> 50]]> <br/><![CDATA[atgttcgtct tcctggtgct gctgcccctg gtgtccagca tcactaacct gtgccccttc 60 ggagaggtct tcaacgccac ccgcttcgct tccgtgtacg cctggaacag gaagagaatc 120 tcaaactgcg tcgctgacta ctccgtgctg tacaactcag cctccttcag caccttcaag 180 tgctacggcg tgtcaccaac taagctgaac gacctgtgct tcaccaacgt ctacgccgac 240 tccttcgtga tcaggggaga cgaggtcaga cagatcgctc ctggccagac tggaaagatc 300 gccgactaca actacaagct gcccgacgac ttcaccggtt gcgtcatcgc ttggaacagc 360 aacaacctgg actctaaagt gggtggcaac tacaactacc tgtaccgcct gttccgtaag 420 tcaaacctga agccattcga gagggacatc agcactgaaa tctaccaggc cggatctacc 480 ccttgcaacg gtgtcgaggg cttcaactgc tacttccccc tgcagtccta cggtttccag 540 ccaactaacg gtgtgggcta ccagccttac agagtggtcg tgctgagctt cgaactgctc 600 cacgctcctg ctactgtgtg cggtccaaag aagtctacca acctggtcaa gaacaagtgc 660 gtgaacttca acttcaacgg cctgaccgga actggtgtcc tgaccgagag caacaagaag 720 ttcctgccct tccagcagtt cggaagggac atcgctgaca ccactgacgc tgtgcgcgac 780 cctcagaccc tggaaatcct ggacatcact ccatgctcat tcggaggtgt ctccgtgatc 840 acccctggca ccaacacttc taaccaggtc gctgtgctgt accaggacgt caactgcacc 900 gaggtccctg tggccatcca cgctgaccag ctgaccccca cttggcgcgt gtactccacc 960 ggcagcaacg tgttccagac tcgtgctggt tgcctgatcg gcgccgagca cgtgaacaac 1020 agctacgaat gcgacatccc catcggcgct ggaatctgcg cctcttacca gacccagact 1080 aacagcccac gcagggctcg ctctgtggcc tctcagtcaa tcatcgctta caccatgtca 1140 ctgggcgctg aaaactccgt ggcctactct aacaactcaa tcgccatccc caccaacttc 1200 actatcagcg tgaccactga gatcctgcca gtcagcatga ccaagacttc tgtggactgc 1260 actatgtaca tctgcggaga cagcaccgaa tgctctaacc tgctgctgca gtacggctct 1320 ttctgcaccc agctgaaccg tgctctgact ggaatcgccg tggagcagga caagaacact 1380 caggaagtct tcgctcaggt gaagcaaatc tacaagaccc cacctatcaa ggacttcggc 1440 ggattcaact tctcccagat cctgcctgac ccctccaagc caagcaagcg ctctttcatc 1500 gaggacctgc tgttcaacaa ggtcactctg gccgacgctg gattcatcaa gcagtacgga 1560 gactgcctgg gtgacatcgc cgctcgtgac ctgatctgcg ctcagaagtt caacggtctg 1620 accgtgctgc ccccactgct gactgacgaa atgatcgccc agtacactag cgccctgctg 1680 gctggaacca tcacttctgg ttggaccttc ggtgctggcg ccgctctgca gatccctttc 1740 gctatgcaga tggcctaccg tttcaacgga atcggtgtca cccagaacgt gctgtacgag 1800 aaccagaagc tgatcgctaa ccagttcaac tcagccatcg gaaagatcca ggacagcctg 1860 agctctactg cctctgctct gggcaagctg caggacgtcg tgaaccagaa cgcccaggct 1920 ctgaacaccc tggtcaagca gctgtcatcc aacttcggtg ctatcagctc tgtgctgaac 1980 gacatcctgt cccgcctgga caaggtcgag gccgaagtgc agatcgaccg cctgatcact 2040 ggccgtctgc agtcactgca gacctacgtg actcagcagc tgatcagggc cgctgaaatc 2100 agagcctccg ctaacctggc cgctaccaag atgagcgagt gcgtcctggg tcaatctaag 2160 cgtgtggact tctgcggcaa gggataccac ctgatgtcat tccctcagtc tgctccccac 2220 ggtgtggtgt tcctgcacgt cacctacgtg ccagcccagg agaagaactt caccactgcc 2280 cctgctatct gccacgacgg caaggctcac ttccccaggg aaggtgtctt cgtgagcaac 2340 ggcacccact ggttcgtcac tcagagaaac ttctacgagc cacagatcat caccactgac 2400 aacactttcg tgtctggaaa ctgcgacgtg gtcatcggta tcgtcaacaa caccgtgtac 2460 gaccccctgc agccagagct ggactcattc aaggaggaac tggacaagta cttcaagaac 2520 cacacctccc ctgacgtcga cctgggcgac atctcaggaa tcaacgcttc cgtcgtgaac 2580 atccagaagg agatcgaccg cctgaacgaa gtggccaaga acctgaacga aagcctgatc 2640 gacctgcagg agctgggcaa gtacgaacag tacatcaagt ggccttggta catctggctg 2700 ggtttcatcg ctggcctcat cgctatcgtg atggtgacca tcatgctgtg ctgcatgact 2760 tcatgctgct cctgcctgaa gggctgctgc agctgcggat cttgctgcaa gttcgacgag 2820 gacgactctg aacccgtcct gaagggcgtg aagctgcact acacccacca ccaccaccac 2880 cac 2883 <![CDATA[<210> 51]]> <![CDATA[<211> 947]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 51]]> Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 1 5 10 15 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 20 25 30 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 35 40 45 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 50 55 60 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 65 70 75 80 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 85 90 95 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 100 105 110 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 115 120 125 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 130 135 140 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 145 150 155 160 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 165 170 175 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 180 185 190 Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val 195 200 205 Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser 210 215 220 Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp 225 230 235 240 Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile 245 250 255 Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn 260 265 270 Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu 275 280 285 Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val 290 295 300 Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile 305 310 315 320 Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly 325 330 335 Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg 340 345 350 Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu 355 360 365 Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro 370 375 380 Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met 385 390 395 400 Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr 405 410 415 Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu 420 425 430 Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln 435 440 445 Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys 450 455 460 Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys 465 470 475 480 Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr 485 490 495 Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp 500 505 510 Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr 515 520 525 Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser 530 535 540 Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly 545 550 555 560 Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn 565 570 575 Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile 580 585 590 Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser 595 600 605 Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn 610 615 620 Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly 625 630 635 640 Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val 645 650 655 Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser 660 665 670 Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 675 680 685 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly 690 695 700 Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 705 710 715 720 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 725 730 735 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 740 745 750 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 755 760 765 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 770 775 780 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 785 790 795 800 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser 805 810 815 Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp 820 825 830 Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile 835 840 845 Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu 850 855 860 Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 865 870 875 880 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile 885 890 895 Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 900 905 910 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp 915 920 925 Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr His His 930 935 940 His His His 945 <![CDATA[<210> 52]]> <![CDATA[<211> 901]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 52]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Ile Thr Asn 1 5 10 15 Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val 20 25 30 Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser 35 40 45 Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val 50 55 60 Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp 65 70 75 80 Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln 85 90 95 Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr 100 105 110 Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly 115 120 125 Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys 130 135 140 Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr 145 150 155 160 Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser 165 170 175 Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val 180 185 190 Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly 195 200 205 Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn 210 215 220 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys 225 230 235 240 Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp 245 250 255 Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys 260 265 270 Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn 275 280 285 Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val 290 295 300 Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr 305 310 315 320 Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu 325 330 335 His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 340 345 350 Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser 355 360 365 Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu 370 375 380 Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe 385 390 395 400 Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr 405 410 415 Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser 420 425 430 Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala 435 440 445 Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe 450 455 460 Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly 465 470 475 480 Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys 485 490 495 Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp 500 505 510 Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala 515 520 525 Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro 530 535 540 Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu 545 550 555 560 Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu 565 570 575 Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly 580 585 590 Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln 595 600 605 Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala 610 615 620 Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala 625 630 635 640 Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser 645 650 655 Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu 660 665 670 Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr 675 680 685 Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 690 695 700 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 705 710 715 720 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 725 730 735 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 740 745 750 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 755 760 765 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp 770 775 780 Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp 785 790 795 800 Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn 805 810 815 Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu 820 825 830 Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 835 840 845 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 850 855 860 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 865 870 875 880 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His 885 890 895 His His His His His 900 <![CDATA[<210> 53]]> <![CDATA[<211> 2706]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 53]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagca tcactaacct gtgccccttc 60 ggagaggtct tcaacgccac ccgcttcgct tccgtgtacg cctggaacag gaagagaatc 120 tcaaactgcg tcgctgacta ctccgtgctg tacaactcag cctccttcag caccttcaag 180 tgctacggcg tgtcaccaac taagctgaac gacctgtgct tcaccaacgt ctacgccgac 240 tccttcgtga tcaggggaga cgaggtcaga cagatcgctc ctggccagac tggaaagatc 300 gccgactaca actacaagct gcccgacgac ttcaccggtt gcgtcatcgc ttggaacagc 360 aacaacctgg actctaaagt gggtggcaac tacaactacc tgtaccgcct gttccgtaag 420 tcaaacctga agccattcga gagggacatc agcactgaaa tctaccaggc cggatctacc 480 ccttgcaacg gtgtcgaggg cttcaactgc tacttccccc tgcagtccta cggtttccag 540 ccaactaacg gtgtgggcta ccagccttac agagtggtcg tgctgagctt cgaactgctc 600 cacgctcctg ctactgtgtg cggtccaaag aagtctacca acctggtcaa gaacaagtgc 660 gtgaacttca acttcaacgg cctgaccgga actggtgtcc tgaccgagag caacaagaag 720 ttcctgccct tccagcagtt cggaagggac atcgctgaca ccactgacgc tgtgcgcgac 780 cctcagaccc tggaaatcct ggacatcact ccatgctcat tcggaggtgt ctccgtgatc 840 acccctggca ccaacacttc taaccaggtc gctgtgctgt accaggacgt caactgcacc 900 gaggtccctg tggccatcca cgctgaccag ctgaccccca cttggcgcgt gtactccacc 960 ggcagcaacg tgttccagac tcgtgctggt tgcctgatcg gcgccgagca cgtgaacaac 1020 agctacgaat gcgacatccc catcggcgct ggaatctgcg cctcttacca gacccagact 1080 aacagcccac gcagggctcg ctctgtggcc tctcagtcaa tcatcgctta caccatgtca 1140 ctgggcgctg aaaactccgt ggcctactct aacaactcaa tcgccatccc caccaacttc 1200 actatcagcg tgaccactga gatcctgcca gtcagcatga ccaagacttc tgtggactgc 1260 actatgtaca tctgcggaga cagcaccgaa tgctctaacc tgctgctgca gtacggctct 1320 ttctgcaccc agctgaaccg tgctctgact ggaatcgccg tggagcagga caagaacact 1380 caggaagtct tcgctcaggt gaagcaaatc tacaagaccc cacctatcaa ggacttcggc 1440 ggattcaact tctcccagat cctgcctgac ccctccaagc caagcaagcg ctctttcatc 1500 gaggacctgc tgttcaacaa ggtcactctg gccgacgctg gattcatcaa gcagtacgga 1560 gactgcctgg gtgacatcgc cgctcgtgac ctgatctgcg ctcagaagtt caacggtctg 1620 accgtgctgc ccccactgct gactgacgaa atgatcgccc agtacactag cgccctgctg 1680 gctggaacca tcacttctgg ttggaccttc ggtgctggcg ccgctctgca gatccctttc 1740 gctatgcaga tggcctaccg tttcaacgga atcggtgtca cccagaacgt gctgtacgag 1800 aaccagaagc tgatcgctaa ccagttcaac tcagccatcg gaaagatcca ggacagcctg 1860 agctctactg cctctgctct gggcaagctg caggacgtcg tgaaccagaa cgcccaggct 1920 ctgaacaccc tggtcaagca gctgtcatcc aacttcggtg ctatcagctc tgtgctgaac 1980 gacatcctgt cccgcctgga caaggtcgag gccgaagtgc agatcgaccg cctgatcact 2040 ggccgtctgc agtcactgca gacctacgtg actcagcagc tgatcagggc cgctgaaatc 2100 agagcctccg ctaacctggc cgctaccaag atgagcgagt gcgtcctggg tcaatctaag 2160 cgtgtggact tctgcggcaa gggataccac ctgatgtcat tccctcagtc tgctccccac 2220 ggtgtggtgt tcctgcacgt cacctacgtg ccagcccagg agaagaactt caccactgcc 2280 cctgctatct gccacgacgg caaggctcac ttccccaggg aaggtgtctt cgtgagcaac 2340 ggcacccact ggttcgtcac tcagagaaac ttctacgagc cacagatcat caccactgac 2400 aacactttcg tgtctggaaa ctgcgacgtg gtcatcggta tcgtcaacaa caccgtgtac 2460 gaccccctgc agccagagct ggactcattc aaggaggaac tggacaagta cttcaagaac 2520 cacacctccc ctgacgtcga cctgggcgac atctcaggaa tcaacgcttc cgtcgtgaac 2580 atccagaagg agatcgaccg cctgaacgaa gtggccaaga acctgaacga aagcctgatc 2640 gacctgcagg agctgggcaa gtacgaacag tacatcaagt ggcctcacca ccaccaccac 2700 caccac 2706 <![CDATA[<210> 54]]> <![CDATA[<211> 888]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 54]]> Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 1 5 10 15 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 20 25 30 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 35 40 45 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 50 55 60 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 65 70 75 80 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 85 90 95 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 100 105 110 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 115 120 125 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 130 135 140 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 145 150 155 160 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 165 170 175 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 180 185 190 Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val 195 200 205 Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser 210 215 220 Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp 225 230 235 240 Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile 245 250 255 Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn 260 265 270 Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu 275 280 285 Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val 290 295 300 Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile 305 310 315 320 Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly 325 330 335 Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg 340 345 350 Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu 355 360 365 Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro 370 375 380 Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met 385 390 395 400 Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr 405 410 415 Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu 420 425 430 Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln 435 440 445 Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys 450 455 460 Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys 465 470 475 480 Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr 485 490 495 Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp 500 505 510 Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr 515 520 525 Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser 530 535 540 Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly 545 550 555 560 Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn 565 570 575 Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile 580 585 590 Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser 595 600 605 Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn 610 615 620 Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly 625 630 635 640 Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val 645 650 655 Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser 660 665 670 Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 675 680 685 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly 690 695 700 Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 705 710 715 720 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 725 730 735 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 740 745 750 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 755 760 765 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 770 775 780 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 785 790 795 800 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser 805 810 815 Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp 820 825 830 Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile 835 840 845 Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu 850 855 860 Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 865 870 875 880 Trp Pro His His His His His His 885 <![CDATA[<210> 55]]> <![CDATA[<211> 3819]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 55]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacagcagg ctcagtctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctt ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tctgaacccg tcctgaaggg cgtgaagctg cactacacc 3819 <![CDATA[<210> 56]]> <![CDATA[<211> 1279]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 56]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr His His His His His 1265 1270 1275 His <![CDATA[<210> 57]]> <![CDATA[<211> 3837]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 57]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacagcagg ctcagtctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctt ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tctgaacccg tcctgaaggg cgtgaagctg cactacaccc accaccacca ccaccac 3837 <![CDATA[<210> 58]]> <![CDATA[<211> 1266]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 58]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr His His His 1250 1255 1260 His His His 1265 <![CDATA[<210> 59]]> <![CDATA[<211> 1219]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 59]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His His His 1205 1210 1215 His <![CDATA[<210> 60]]> <![CDATA[<211> 3657]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 60]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacagcagg ctcagtctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctc accaccacca ccaccac 3657 <![CDATA[<210> 61]]> <![CDATA[<211> 1205]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 61]]> Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn 1 5 10 15 Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser 20 25 30 Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val 35 40 45 Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg 50 55 60 Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser 65 70 75 80 Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu 85 90 95 Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val 100 105 110 Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly 115 120 125 Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg 130 135 140 Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro 145 150 155 160 Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg 165 170 175 Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys 180 185 190 His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala 195 200 205 Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe 210 215 220 Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser 225 230 235 240 Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu 245 250 255 Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr 260 265 270 Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr 275 280 285 Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe 290 295 300 Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn 305 310 315 320 Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val 325 330 335 Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser 340 345 350 Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val 355 360 365 Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp 370 375 380 Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln 385 390 395 400 Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr 405 410 415 Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly 420 425 430 Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys 435 440 445 Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr 450 455 460 Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser 465 470 475 480 Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val 485 490 495 Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly 500 505 510 Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn 515 520 525 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys 530 535 540 Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp 545 550 555 560 Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys 565 570 575 Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn 580 585 590 Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val 595 600 605 Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr 610 615 620 Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu 625 630 635 640 His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 645 650 655 Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser 660 665 670 Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu 675 680 685 Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe 690 695 700 Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr 705 710 715 720 Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser 725 730 735 Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala 740 745 750 Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe 755 760 765 Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly 770 775 780 Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys 785 790 795 800 Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp 805 810 815 Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala 820 825 830 Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro 835 840 845 Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu 850 855 860 Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu 865 870 875 880 Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly 885 890 895 Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln 900 905 910 Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala 915 920 925 Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala 930 935 940 Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser 945 950 955 960 Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu 965 970 975 Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr 980 985 990 Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 995 1000 1005 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser 1010 1015 1020 Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe 1025 1030 1035 Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 1040 1045 1050 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys 1055 1060 1065 His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser 1070 1075 1080 Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro 1085 1090 1095 Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp 1100 1105 1110 Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln 1115 1120 1125 Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys 1130 1135 1140 Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile 1145 1150 1155 Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn 1160 1165 1170 Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu 1175 1180 1185 Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His His 1190 1195 1200 His His 1205 <![CDATA[<210> 62]]> <![CDATA[<211> 1263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 62]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile 690 695 700 Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser 705 710 715 720 Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser 725 730 735 Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln 740 745 750 Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr 755 760 765 Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile 770 775 780 Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser 785 790 795 800 Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val 805 810 815 Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly 820 825 830 Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu 835 840 845 Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr 850 855 860 Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala 865 870 875 880 Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe 885 890 895 Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu 900 905 910 Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu 915 920 925 Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln 930 935 940 Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe 945 950 955 960 Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys 965 970 975 Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln 980 985 990 Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile 995 1000 1005 Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val 1010 1015 1020 Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His 1025 1030 1035 Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu 1040 1045 1050 His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala 1055 1060 1065 Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly 1070 1075 1080 Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn 1085 1090 1095 Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser 1100 1105 1110 Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1115 1120 1125 Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp 1130 1135 1140 Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1145 1150 1155 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1160 1165 1170 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 1175 1180 1185 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val 1205 1210 1215 Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 1220 1225 1230 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu 1235 1240 1245 Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 63]]> <![CDATA[<211> 1250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 63]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser 675 680 685 Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu 690 695 700 Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys 705 710 715 720 Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe 725 730 735 Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp 740 745 750 Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr 755 760 765 Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro 770 775 780 Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe 785 790 795 800 Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp 805 810 815 Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe 820 825 830 Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala 835 840 845 Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr 850 855 860 Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala 865 870 875 880 Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn 885 890 895 Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln 900 905 910 Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val 915 920 925 Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser 930 935 940 Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg 945 950 955 960 Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly 965 970 975 Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala 980 985 990 Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 995 1000 1005 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1010 1015 1020 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1025 1030 1035 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1040 1045 1050 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1055 1060 1065 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1070 1075 1080 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1085 1090 1095 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1100 1105 1110 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1115 1120 1125 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1130 1135 1140 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1145 1150 1155 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1160 1165 1170 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1175 1180 1185 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1190 1195 1200 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1205 1210 1215 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1220 1225 1230 Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His 1235 1240 1245 Tyr Thr 1250 <![CDATA[<210> 64]]> <![CDATA[<211> 1263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 64]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Glu Ile Leu Pro Val Ser 705 710 715 720 Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser 725 730 735 Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln 740 745 750 Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr 755 760 765 Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile 770 775 780 Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser 785 790 795 800 Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val 805 810 815 Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly 820 825 830 Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu 835 840 845 Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr 850 855 860 Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala 865 870 875 880 Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe 885 890 895 Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu 900 905 910 Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu 915 920 925 Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln 930 935 940 Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe 945 950 955 960 Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys 965 970 975 Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln 980 985 990 Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile 995 1000 1005 Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val 1010 1015 1020 Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His 1025 1030 1035 Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu 1040 1045 1050 His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala 1055 1060 1065 Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly 1070 1075 1080 Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn 1085 1090 1095 Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser 1100 1105 1110 Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1115 1120 1125 Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp 1130 1135 1140 Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1145 1150 1155 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1160 1165 1170 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 1175 1180 1185 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val 1205 1210 1215 Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 1220 1225 1230 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu 1235 1240 1245 Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 65]]> <![CDATA[<211> 1250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 65]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Glu Ile Leu 690 695 700 Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys 705 710 715 720 Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe 725 730 735 Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp 740 745 750 Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr 755 760 765 Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro 770 775 780 Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe 785 790 795 800 Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp 805 810 815 Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe 820 825 830 Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala 835 840 845 Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr 850 855 860 Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala 865 870 875 880 Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn 885 890 895 Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln 900 905 910 Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val 915 920 925 Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser 930 935 940 Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg 945 950 955 960 Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly 965 970 975 Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala 980 985 990 Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 995 1000 1005 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1010 1015 1020 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1025 1030 1035 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1040 1045 1050 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1055 1060 1065 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1070 1075 1080 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1085 1090 1095 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1100 1105 1110 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1115 1120 1125 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1130 1135 1140 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1145 1150 1155 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1160 1165 1170 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1175 1180 1185 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1190 1195 1200 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1205 1210 1215 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1220 1225 1230 Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His 1235 1240 1245 Tyr Thr 1250 <![CDATA[<210> 66]]> <![CDATA[<211> 1263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 66]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly 820 825 830 Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu 835 840 845 Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr 850 855 860 Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala 865 870 875 880 Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe 885 890 895 Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu 900 905 910 Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu 915 920 925 Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln 930 935 940 Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe 945 950 955 960 Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys 965 970 975 Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln 980 985 990 Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile 995 1000 1005 Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val 1010 1015 1020 Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His 1025 1030 1035 Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu 1040 1045 1050 His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala 1055 1060 1065 Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly 1070 1075 1080 Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn 1085 1090 1095 Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser 1100 1105 1110 Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1115 1120 1125 Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp 1130 1135 1140 Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1145 1150 1155 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1160 1165 1170 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 1175 1180 1185 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val 1205 1210 1215 Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 1220 1225 1230 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu 1235 1240 1245 Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 67]]> <![CDATA[<211> 1250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 67]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp 805 810 815 Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe 820 825 830 Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala 835 840 845 Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr 850 855 860 Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala 865 870 875 880 Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn 885 890 895 Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln 900 905 910 Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val 915 920 925 Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser 930 935 940 Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg 945 950 955 960 Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly 965 970 975 Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala 980 985 990 Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 995 1000 1005 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1010 1015 1020 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1025 1030 1035 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1040 1045 1050 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1055 1060 1065 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1070 1075 1080 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1085 1090 1095 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1100 1105 1110 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1115 1120 1125 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1130 1135 1140 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1145 1150 1155 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1160 1165 1170 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1175 1180 1185 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1190 1195 1200 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1205 1210 1215 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1220 1225 1230 Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His 1235 1240 1245 Tyr Thr 1250 <![CDATA[<210> 68]]> <![CDATA[<211> 31]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 折疊子]]> <![CDATA[<400> 68]]> Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala 1 5 10 15 Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 20 25 30 <![CDATA[<210> 69]]> <![CDATA[<211> 202]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 69]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys 195 200 <![CDATA[<210> 70]]> <![CDATA[<211> 201]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸道症候群相關冠狀病毒]]> <![CDATA[<400> 70]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg 100 105 110 Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr 115 120 125 Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val 130 135 140 Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys 145 150 155 160 Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly 165 170 175 Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala 180 185 190 Pro Ala Thr Val Cys Gly Pro Lys Leu 195 200 <![CDATA[<210> 71]]> <![CDATA[<211> 239]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒中東呼吸道症候群相關冠狀病毒]]> <![CDATA[<400> 71]]> Phe Glu Ala Lys Pro Ser Gly Ser Val Val Ala Glu Gly Val Glu Cys 1 5 10 15 Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe 20 25 30 Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu 35 40 45 Ser Leu Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala 50 55 60 Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser 65 70 75 80 Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro 85 90 95 Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu 100 105 110 Ile Leu Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu 115 120 125 Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg Leu Leu Ser Asp Asp Arg 130 135 140 Thr Glu Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val 145 150 155 160 Ser Ile Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys 165 170 175 Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser 180 185 190 Thr Val Ala Met Thr Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val 195 200 205 Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala 210 215 220 Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr 225 230 235 <![CDATA[<210> 72]]> <![CDATA[<211> 544]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 72]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys 210 215 220 Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu 225 230 235 240 Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala 245 250 255 Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp 260 265 270 Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr 275 280 285 Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr 290 295 300 Glu Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe 305 310 315 320 Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile 325 330 335 Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe 340 345 350 Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu 355 360 365 Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu 370 375 380 Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn 385 390 395 400 Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser 405 410 415 Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg 420 425 430 Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr 435 440 445 Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe 450 455 460 Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly 465 470 475 480 Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu 485 490 495 His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Ala Ile Gly Gly 500 505 510 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp 515 520 525 Gly Glu Trp Val Leu Leu Ser Thr Phe Leu His His His His His His 530 535 540 <![CDATA[<210> 73]]> <![CDATA[<211> 531]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> ]]>重組纖突蛋白 <![CDATA[<400> 73]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys 195 200 205 Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val 210 215 220 Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg 225 230 235 240 Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu 245 250 255 Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr 260 265 270 Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val 275 280 285 Asn Cys Thr Glu Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 290 295 300 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 305 310 315 320 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 325 330 335 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 340 345 350 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 355 360 365 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 370 375 380 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 385 390 395 400 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 405 410 415 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 420 425 430 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 435 440 445 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 450 455 460 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 465 470 475 480 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Ala 485 490 495 Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val 500 505 510 Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu His His His 515 520 525 His His His 530 <![CDATA[<210> 74]]> <![CDATA[<211> 544]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 74]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys 210 215 220 Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu 225 230 235 240 Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala 245 250 255 Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp 260 265 270 Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr 275 280 285 Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr 290 295 300 Glu Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe 305 310 315 320 Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile 325 330 335 Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe 340 345 350 Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu 355 360 365 Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu 370 375 380 Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn 385 390 395 400 Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser 405 410 415 Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg 420 425 430 Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr 435 440 445 Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe 450 455 460 Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly 465 470 475 480 Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu 485 490 495 His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Ala Ile Gly Gly 500 505 510 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp 515 520 525 Gly Glu Trp Val Leu Leu Ser Thr Phe Leu His His His His His His 530 535 540 <![CDATA[<210> 75]]> <![CDATA[<211> 531]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 75]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys 195 200 205 Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val 210 215 220 Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg 225 230 235 240 Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu 245 250 255 Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr 260 265 270 Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val 275 280 285 Asn Cys Thr Glu Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 290 295 300 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 305 310 315 320 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 325 330 335 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 340 345 350 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 355 360 365 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 370 375 380 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 385 390 395 400 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 405 410 415 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 420 425 430 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 435 440 445 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 450 455 460 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 465 470 475 480 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Ala 485 490 495 Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val 500 505 510 Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu His His His 515 520 525 His His His 530 <![CDATA[<210> 76]]> <![CDATA[<211> 470]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 76]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly Gly Gly Ser 210 215 220 Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile Thr Asn Leu 225 230 235 240 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr 245 250 255 Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 260 265 270 Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 275 280 285 Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser 290 295 300 Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr 305 310 315 320 Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly 325 330 335 Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly 340 345 350 Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro 355 360 365 Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro 370 375 380 Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly 385 390 395 400 Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val 405 410 415 Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys 420 425 430 Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln 435 440 445 Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 450 455 460 His His His His His His 465 470 <![CDATA[<210> 77]]> <![CDATA[<211> 464]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 77]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly Gly Gly Ser 210 215 220 Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile Thr Asn Leu 225 230 235 240 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr 245 250 255 Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 260 265 270 Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 275 280 285 Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser 290 295 300 Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr 305 310 315 320 Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly 325 330 335 Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly 340 345 350 Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro 355 360 365 Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro 370 375 380 Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly 385 390 395 400 Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val 405 410 415 Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys 420 425 430 Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln 435 440 445 Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 450 455 460 <![CDATA[<210> 78]]> <![CDATA[<211> 457]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 78]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly 195 200 205 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile 210 215 220 Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro 225 230 235 240 Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp 245 250 255 Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr 260 265 270 Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr 275 280 285 Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro 290 295 300 Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 305 310 315 320 Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr 325 330 335 Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys 340 345 350 Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp 355 360 365 Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn 370 375 380 Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg 385 390 395 400 Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys 405 410 415 Gly Pro Lys Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg 420 425 430 Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser 435 440 445 Thr Phe Leu His His His His His His 450 455 <![CDATA[<210> 79]]> <![CDATA[<211> 451]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 79]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly 195 200 205 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile 210 215 220 Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro 225 230 235 240 Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp 245 250 255 Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr 260 265 270 Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr 275 280 285 Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro 290 295 300 Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 305 310 315 320 Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr 325 330 335 Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys 340 345 350 Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp 355 360 365 Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn 370 375 380 Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg 385 390 395 400 Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys 405 410 415 Gly Pro Lys Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg 420 425 430 Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser 435 440 445 Thr Phe Leu 450 <![CDATA[<210> 80]]> <![CDATA[<211> 726]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 80]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly Gly Gly Ser 210 215 220 Gly Gly Gly Ser Gly Gly Gly Ser Phe Glu Ala Lys Pro Ser Gly Ser 225 230 235 240 Val Val Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly 245 250 255 Thr Pro Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys 260 265 270 Asn Tyr Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe 275 280 285 Thr Cys Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser 290 295 300 Ser Leu Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp 305 310 315 320 Leu Ser Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln 325 330 335 Ser Phe Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn 340 345 350 Leu Thr Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys 355 360 365 Ser Arg Leu Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn 370 375 380 Ala Asn Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp 385 390 395 400 Glu Asp Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly 405 410 415 Gly Trp Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu 420 425 430 Gln Met Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser 435 440 445 Val Cys Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln 450 455 460 Leu Gly Asn Cys Val Glu Tyr Ser Gly Gly Gly Ser Gly Gly Gly Ser 465 470 475 480 Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile Thr Asn Leu 485 490 495 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr 500 505 510 Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 515 520 525 Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 530 535 540 Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser 545 550 555 560 Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr 565 570 575 Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly 580 585 590 Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly 595 600 605 Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro 610 615 620 Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro 625 630 635 640 Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly 645 650 655 Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val 660 665 670 Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys 675 680 685 Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln 690 695 700 Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 705 710 715 720 His His His His His His 725 <![CDATA[<210> 81]]> <![CDATA[<211> 720]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 81]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Arg Phe Pro 1 5 10 15 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 20 25 30 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 35 40 45 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 50 55 60 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 65 70 75 80 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 85 90 95 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 100 105 110 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 115 120 125 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 130 135 140 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 145 150 155 160 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 165 170 175 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 180 185 190 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 195 200 205 Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly Gly Gly Ser 210 215 220 Gly Gly Gly Ser Gly Gly Gly Ser Phe Glu Ala Lys Pro Ser Gly Ser 225 230 235 240 Val Val Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly 245 250 255 Thr Pro Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys 260 265 270 Asn Tyr Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe 275 280 285 Thr Cys Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser 290 295 300 Ser Leu Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp 305 310 315 320 Leu Ser Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln 325 330 335 Ser Phe Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn 340 345 350 Leu Thr Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys 355 360 365 Ser Arg Leu Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn 370 375 380 Ala Asn Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp 385 390 395 400 Glu Asp Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly 405 410 415 Gly Trp Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu 420 425 430 Gln Met Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser 435 440 445 Val Cys Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln 450 455 460 Leu Gly Asn Cys Val Glu Tyr Ser Gly Gly Gly Ser Gly Gly Gly Ser 465 470 475 480 Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile Thr Asn Leu 485 490 495 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr 500 505 510 Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 515 520 525 Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 530 535 540 Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser 545 550 555 560 Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr 565 570 575 Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly 580 585 590 Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly 595 600 605 Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro 610 615 620 Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro 625 630 635 640 Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly 645 650 655 Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val 660 665 670 Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys 675 680 685 Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln 690 695 700 Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 705 710 715 720 <![CDATA[<210> 82]]> <![CDATA[<211> 713]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 82]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly 195 200 205 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Phe Glu Ala Lys Pro 210 215 220 Ser Gly Ser Val Val Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu 225 230 235 240 Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe 245 250 255 Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val 260 265 270 Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn 275 280 285 Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met 290 295 300 Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn 305 310 315 320 Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val 325 330 335 Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile 340 345 350 Asn Lys Cys Ser Arg Leu Leu Ser Asp Asp Arg Thr Glu Val Pro Gln 355 360 365 Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser 370 375 380 Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu 385 390 395 400 Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr 405 410 415 Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp 420 425 430 Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile 435 440 445 Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Gly Gly Gly Ser Gly 450 455 460 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile 465 470 475 480 Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro 485 490 495 Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp 500 505 510 Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr 515 520 525 Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr 530 535 540 Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro 545 550 555 560 Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 565 570 575 Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr 580 585 590 Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys 595 600 605 Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp 610 615 620 Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn 625 630 635 640 Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg 645 650 655 Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys 660 665 670 Gly Pro Lys Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg 675 680 685 Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser 690 695 700 Thr Phe Leu His His His His His His 705 710 <![CDATA[<210> 83]]> <![CDATA[<211> 707]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 83]]> Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Gly Gly Gly Ser Gly 195 200 205 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Phe Glu Ala Lys Pro 210 215 220 Ser Gly Ser Val Val Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu 225 230 235 240 Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe 245 250 255 Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val 260 265 270 Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn 275 280 285 Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met 290 295 300 Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn 305 310 315 320 Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val 325 330 335 Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile 340 345 350 Asn Lys Cys Ser Arg Leu Leu Ser Asp Asp Arg Thr Glu Val Pro Gln 355 360 365 Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser 370 375 380 Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu 385 390 395 400 Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr 405 410 415 Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp 420 425 430 Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile 435 440 445 Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Gly Gly Gly Ser Gly 450 455 460 Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Phe Pro Asn Ile 465 470 475 480 Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro 485 490 495 Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp 500 505 510 Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr 515 520 525 Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr 530 535 540 Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro 545 550 555 560 Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 565 570 575 Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr 580 585 590 Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys 595 600 605 Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp 610 615 620 Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn 625 630 635 640 Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg 645 650 655 Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys 660 665 670 Gly Pro Lys Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg 675 680 685 Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser 690 695 700 Thr Phe Leu 705 <![CDATA[<210> 84]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 84]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 85]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 85]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 86]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 86]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 87]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 87]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 88]]> <![CDATA[<211> 1219]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 88]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His His His 1205 1210 1215 His <![CDATA[<210> 89]]> <![CDATA[<211> 1206]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220]]>>]]> <br/><![CDATA[<223> 重組纖突蛋白]]> <br/> <br/><![CDATA[<400> 89]]> <br/> <br/><![CDATA[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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro His His His 1190 1195 1200 His His His 1205 <![CDATA[<210> 90]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 90]]> Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 1 5 10 15 Ser <![CDATA[<210> 91]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 91]]> Ser Gly Gly Gly 1 <![CDATA[<210> 92]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 92]]> Gly Gly Gly Ser 1 <![CDATA[<210> 93]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400>]]> 93 Gly Gly Gly Gly Ser 1 5 <![CDATA[<210> 94]]> <![CDATA[<211> 90]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 94]]> Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly 1 5 10 15 Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro 20 25 30 Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg 35 40 45 Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly 50 55 60 Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala 65 70 75 80 Val Leu Tyr Gln Asp Val Asn Cys Thr Glu 85 90 <![CDATA[<210> 95]]> <![CDATA[<211> 3639]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 95]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacgcaggg ctcgctctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggacaaggt cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcct 3639 <![CDATA[<210> 96]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 96]]> atgttcgtct tcctggtgct gctgcccctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcactc gcggtgtgta ctaccctgac 120 aaggtcttcc gttcttcagt gctgcactca actcaggacc tgttcctgcc cttcttctcc 180 aacgtcacct ggttccacgc catccacgtg tccggcacca acggcactaa gcgcttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atccgtggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtc tgcgaattcc agttctgcaa cgacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgagg gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt acagcaagca caccccaatc aacctggtgc gcgacctgcc tcagggtttc 660 tctgctctgg agccactggt ggacctgcct atcggcatca acatcacccg cttccagact 720 ctgctggctc tgcaccgttc ctacctgact ccaggcgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggctacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggaa ccatcactga cgccgtcgac tgcgctctgg accctctgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggcatctacc agacttcaaa cttcagggtg 960 cagcccaccg aatccatcgt cagattccct aacatcacta acctgtgccc cttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga acaggaagag aatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggcgtgtcac caactaagct gaacgacctg tgcttcacca acgtctacgc cgactccttc 1200 gtgatcaggg gagacgaggt cagacagatc gctcctggcc agactggaaa gatcgccgac 1260 tacaactaca agctgcccga cgacttcacc ggttgcgtca tcgcttggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtacc gcctgttccg taagtcaaac 1380 ctgaagccat tcgagaggga catcagcact gaaatctacc aggccggatc taccccttgc 1440 aacggtgtcg agggcttcaa ctgctacttc cccctgcagt cctacggttt ccagccaact 1500 aacggtgtgg gctaccagcc ttacagagtg gtcgtgctga gcttcgaact gctccacgct 1560 cctgctactg tgtgcggtcc aaagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cccttccagc agttcggaag ggacatcgct gacaccactg acgctgtgcg cgaccctcag 1740 accctggaaa tcctggacat cactccatgc tcattcggag gtgtctccgt gatcacccct 1800 ggcaccaaca cttctaacca ggtcgctgtg ctgtaccagg acgtcaactg caccgaggtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttggc gcgtgtactc caccggcagc 1920 aacgtgttcc agactcgtgc tggttgcctg atcggcgccg agcacgtgaa caacagctac 1980 gaatgcgaca tccccatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccacagcagg ctcagtctgt ggcctctcag tcaatcatcg cttacaccat gtcactgggc 2100 gctgaaaact ccgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga accgtgctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagccaagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggattca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg tctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gcccagtaca ctagcgccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggcgccgctc tgcagatccc tttcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggaaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggcaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggtgctatca gctctgtgct gaacgacatc 2940 ctgtcccgcc tggaccctcc cgaggccgaa gtgcagatcg accgcctgat cactggccgt 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatca gggccgctga aatcagagcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggtcaatc taagcgtgtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtctgctcc ccacggtgtg 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc agggaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagag aaacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggactc attcaaggag gaactggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg cgacatctca ggaatcaacg cttccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggcc aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggcctt ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tctgaacccg tcctgaaggg cgtgaagctg cactacacct aa 3822 <![CDATA[<210> 97]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 97]]> Gly Ser Ala Ser 1 <![CDATA[<210> 98]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> HRV3C切割位點]]> <![CDATA[<400> 98]]> Leu Glu Val Leu Phe Gln Gly Pro 1 5 <![CDATA[<210> 99]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Strep-標籤]]> <![CDATA[<400> 99]]> Trp Ser His Pro Gln Phe Glu Lys 1 5 <![CDATA[<210> 100]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 6X-H]]>is 標籤 <![CDATA[<400> 100]]> His His His His His His 1 5 <![CDATA[<210> 101]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> His-標籤]]> <![CDATA[<220>]]> <![CDATA[<221> 位點]]> <![CDATA[<222> (6)..(6)]]> <![CDATA[<223> 可以存在或不存在]]> <![CDATA[<220>]]> <![CDATA[<221> 位點]]> <![CDATA[<222> (7)..(7)]]> <![CDATA[<223> 可以存在或不存在]]> <![CDATA[<220>]]> <![CDATA[<221> 位點]]> <![CDATA[<222> (8)..(8)]]> <![CDATA[<223> 可以存在或不存在]]> <![CDATA[<220>]]> <![CDATA[<221> 位點]]> <![CDATA[<222> (9)..(9)]]> <![CDATA[<223> 可以存在或不存在]]> <![CDATA[<220>]]> <![CDATA[<221> 位點]]> <![CDATA[<222> (10)..(10)]]> <![CDATA[<223> 可以存在或不存在]]> <![CDATA[<400> 101]]> His His His His His His His His His His 1 5 10 <![CDATA[<210> 102]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 8X-His 標籤]]> <![CDATA[<400> 102]]> His His His His His His His His 1 5 <![CDATA[<210> 103]]> <![CDATA[<211> 30]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 折疊子]]> <![CDATA[<400> 103]]> Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1 5 10 15 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Ser Pro Ala 20 25 30 <![CDATA[<210> 104]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 104]]> Glu Asp Leu Leu Phe Asn Lys Val Thr Leu 1 5 10 <![CDATA[<210> 105]]> <![CDATA[<211> 1263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 105]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly 820 825 830 Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu 835 840 845 Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr 850 855 860 Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala 865 870 875 880 Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe 885 890 895 Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu 900 905 910 Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu 915 920 925 Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln 930 935 940 Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe 945 950 955 960 Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro 965 970 975 Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln 980 985 990 Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile 995 1000 1005 Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val 1010 1015 1020 Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His 1025 1030 1035 Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu 1040 1045 1050 His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala 1055 1060 1065 Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly 1070 1075 1080 Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn 1085 1090 1095 Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser 1100 1105 1110 Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1115 1120 1125 Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp 1130 1135 1140 Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1145 1150 1155 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1160 1165 1170 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 1175 1180 1185 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val 1205 1210 1215 Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 1220 1225 1230 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu 1235 1240 1245 Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 106]]> <![CDATA[<211> 1250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 106]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp 805 810 815 Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe 820 825 830 Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala 835 840 845 Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr 850 855 860 Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala 865 870 875 880 Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn 885 890 895 Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln 900 905 910 Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val 915 920 925 Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser 930 935 940 Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg 945 950 955 960 Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly 965 970 975 Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala 980 985 990 Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 995 1000 1005 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1010 1015 1020 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1025 1030 1035 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1040 1045 1050 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1055 1060 1065 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1070 1075 1080 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1085 1090 1095 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1100 1105 1110 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1115 1120 1125 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1130 1135 1140 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1145 1150 1155 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1160 1165 1170 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1175 1180 1185 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1190 1195 1200 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1205 1210 1215 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1220 1225 1230 Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His 1235 1240 1245 Tyr Thr 1250 <![CDATA[<210> 107]]> <![CDATA[<211> 1263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 107]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly 820 825 830 Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu 835 840 845 Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr 850 855 860 Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala 865 870 875 880 Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe 885 890 895 Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu 900 905 910 Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu 915 920 925 Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln 930 935 940 Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe 945 950 955 960 Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys 965 970 975 Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln 980 985 990 Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile 995 1000 1005 Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val 1010 1015 1020 Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His 1025 1030 1035 Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu 1040 1045 1050 His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala 1055 1060 1065 Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly 1070 1075 1080 Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn 1085 1090 1095 Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser 1100 1105 1110 Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1115 1120 1125 Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp 1130 1135 1140 Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 1145 1150 1155 Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile 1160 1165 1170 Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile 1175 1180 1185 Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1190 1195 1200 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val 1205 1210 1215 Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys 1220 1225 1230 Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu 1235 1240 1245 Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 108]]> <![CDATA[<211> 1250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組纖突蛋白]]> <![CDATA[<400> 108]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp 805 810 815 Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe 820 825 830 Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala 835 840 845 Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr 850 855 860 Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala 865 870 875 880 Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn 885 890 895 Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln 900 905 910 Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val 915 920 925 Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser 930 935 940 Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg 945 950 955 960 Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly 965 970 975 Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala 980 985 990 Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 995 1000 1005 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1010 1015 1020 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1025 1030 1035 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1040 1045 1050 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1055 1060 1065 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1070 1075 1080 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1085 1090 1095 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1100 1105 1110 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1115 1120 1125 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1130 1135 1140 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1145 1150 1155 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1160 1165 1170 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1175 1180 1185 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1190 1195 1200 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1205 1210 1215 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1220 1225 1230 Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His 1235 1240 1245 Tyr Thr 1250 <![CDATA[<210> 109]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組CoV S多肽]]> <![CDATA[<400> 109]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 110]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組CoV S多肽]]> <![CDATA[<400> 110]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 111]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組弗林蛋白酶切割位點]]> <![CDATA[<400> 111]]> Gly Ser Gly Ala 1 <![CDATA[<210> 112]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2纖突蛋白]]> <![CDATA[<400> 112]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 113]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2纖突蛋白]]> <![CDATA[<400> 113]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 114]]> <![CDATA[<211> 1257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2纖突蛋白]]> <![CDATA[<400> 114]]> 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 20 25 30 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 Ser Gly Thr Asn Gly Thr Lys Arg Phe 50 55 60 Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr 65 70 75 80 Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp 85 90 95 Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val 100 105 110 Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val 115 120 125 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 130 135 140 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 145 150 155 160 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 165 170 175 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 180 185 190 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 195 200 205 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 210 215 220 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 225 230 235 240 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 245 250 255 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 260 265 270 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 275 280 285 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 290 295 300 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 305 310 315 320 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 325 330 335 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 340 345 350 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 355 360 365 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 370 375 380 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 385 390 395 400 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 405 410 415 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 420 425 430 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 435 440 445 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 450 455 460 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 465 470 475 480 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 485 490 495 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 500 505 510 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 515 520 525 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 530 535 540 Pro Phe Gln Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val 545 550 555 560 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 565 570 575 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 580 585 590 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 595 600 605 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 610 615 620 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 625 630 635 640 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 645 650 655 Ser Tyr Gln Thr Gln Thr Asn Ser His Gln Gln Ala Gln Ser Val Ala 660 665 670 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 675 680 685 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile 690 695 700 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 705 710 715 720 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 725 730 735 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 740 745 750 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 755 760 765 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 770 775 780 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 785 790 795 800 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 805 810 815 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 820 825 830 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 835 840 845 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 850 855 860 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 865 870 875 880 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 885 890 895 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 900 905 910 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 915 920 925 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 930 935 940 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 945 950 955 960 Leu Asn Asp Ile Leu Ala Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 965 970 975 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 980 985 990 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 995 1000 1005 Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg 1010 1015 1020 Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 1025 1030 1035 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro 1040 1045 1050 Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp 1055 1060 1065 Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 1070 1075 1080 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile 1085 1090 1095 Ile Thr Thr His Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val 1100 1105 1110 Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu 1115 1120 1125 Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His 1130 1135 1140 Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala 1145 1150 1155 Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val 1160 1165 1170 Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly 1175 1180 1185 Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly 1190 1195 1200 Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu 1205 1210 1215 Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser 1220 1225 1230 Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 1235 1240 1245 Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 115]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2纖突蛋白]]> <![CDATA[<400> 115]]> 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 20 25 30 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 Ala 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 His 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 Asn 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 435 440 445 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 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 116]]> <![CDATA[<211> 196]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 116]]> Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val 1 5 10 15 Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser 20 25 30 Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val 35 40 45 Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp 50 55 60 Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln 65 70 75 80 Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr 85 90 95 Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly 100 105 110 Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys 115 120 125 Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr 130 135 140 Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser 145 150 155 160 Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val 165 170 175 Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly 180 185 190 Pro Lys Lys Ser 195 <![CDATA[<210> 117]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 信號肽]]> <![CDATA[<400> 117]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ile 1 5 10 <![CDATA[<210> 118]]> <![CDATA[<211> 292]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 118]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 290 <![CDATA[<210> 119]]> <![CDATA[<211> 83]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 11]]>9 Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr 1 5 10 15 Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys 20 25 30 Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln 35 40 45 Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln 50 55 60 Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu 65 70 75 80 Ser Arg Leu <![CDATA[<210> 120]]> <![CDATA[<211> 588]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 120]]> Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 1 5 10 15 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 20 25 30 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 35 40 45 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 50 55 60 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 65 70 75 80 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 85 90 95 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 100 105 110 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 115 120 125 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 130 135 140 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 145 150 155 160 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 165 170 175 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 180 185 190 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 195 200 205 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 210 215 220 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 225 230 235 240 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 245 250 255 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 260 265 270 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 275 280 285 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 290 295 300 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 305 310 315 320 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 325 330 335 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser 340 345 350 Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 355 360 365 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro 370 375 380 Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 385 390 395 400 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His 405 410 415 Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr 420 425 430 Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val 435 440 445 Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys 450 455 460 Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp 465 470 475 480 Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 485 490 495 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 500 505 510 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 515 520 525 Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met 530 535 540 Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys 545 550 555 560 Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 565 570 575 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 580 585 <![CDATA[<210> 121]]> <![CDATA[<211> 672]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 121]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg 660 665 670 <![CDATA[<210> 122]]> <![CDATA[<211> 140]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 122]]> Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 1 5 10 15 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 20 25 30 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 35 40 45 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 50 55 60 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 65 70 75 80 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 85 90 95 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 100 105 110 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 115 120 125 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 130 135 140 <![CDATA[<210> 123]]> <![CDATA[<211> 24]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 123]]> Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met 1 5 10 15 Val Thr Ile Met Leu Cys Cys Met 20 <![CDATA[<210> 124]]> <![CDATA[<211> 36]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 124]]> Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys 1 5 10 15 Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys 20 25 30 Leu His Tyr Thr 35 <![CDATA[<210> 125]]> <![CDATA[<211> 51]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 125]]> Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn 1 5 10 15 Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn 20 25 30 Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile 35 40 45 Lys Trp Pro 50 <![CDATA[<210> 126]]> <![CDATA[<211> 197]]> <![CDATA[<212> PRT]]> <![CDATA[<213> β冠狀病毒重度急性呼吸症候群冠狀病毒2]]> <![CDATA[<400> 126]]> Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 1 5 10 15 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 20 25 30 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 35 40 45 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 50 55 60 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 65 70 75 80 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 85 90 95 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 100 105 110 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 115 120 125 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 130 135 140 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 145 150 155 160 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 165 170 175 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 180 185 190 Thr Val Cys Gly Pro 195 <![CDATA[<210> 127]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 滅活的弗林蛋白酶切割位點]]> <![CDATA[<400> 127]]> Gly Gly Gly 1 <![CDATA[<210> 128]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 滅活的弗林蛋白酶切割位點]]> <![CDATA[<400> 128]]> Gly Gly Gly Gly 1 <![CDATA[<210> 129]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 滅活的弗林蛋白酶切割位點]]> <![CDATA[<400> 129]]> Gly Gly Gly Gly Gly 1 5 <![CDATA[<210> 130]]> <![CDATA[<211> 1272]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 130]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu His Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn 785 790 795 800 Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe 805 810 815 Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe 820 825 830 Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu 835 840 845 Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu 850 855 860 Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr 865 870 875 880 Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro 885 890 895 Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln 900 905 910 Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser 915 920 925 Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu 930 935 940 Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr 945 950 955 960 Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu 965 970 975 Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile 980 985 990 Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr 995 1000 1005 Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 1010 1015 1020 Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg 1025 1030 1035 Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 1040 1045 1050 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro 1055 1060 1065 Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp 1070 1075 1080 Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 1085 1090 1095 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile 1100 1105 1110 Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val 1115 1120 1125 Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu 1130 1135 1140 Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His 1145 1150 1155 Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala 1160 1165 1170 Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val 1175 1180 1185 Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly 1190 1195 1200 Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly 1205 1210 1215 Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu 1220 1225 1230 Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser 1235 1240 1245 Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 1250 1255 1260 Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 131]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 131]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcacta ggggtgtgta ctacccagac 120 aaggtcttcc gctcctcagt gctgcactca actcaggacc tgttcctgcc tttcttctcc 180 aacgtcacct ggttccacgc tatccacgtg tccggcacca acggcactaa gaggttcgcc 240 aaccccgtgc tgccattcaa cgacggagtc tacttcgctt caaccgagaa gtccaacatc 300 atcagaggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcta ccaacgtggt catcaaggtg tgcgaattcc agttctgtaa cgaccccttc 420 ctgggtgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc cattcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgcgc gagttcgtgt tcaagaacat cgacggctac 600 ttcaagattt acagcaagca cacccccatc aacctggtcc gtggcctgcc acagggattc 660 tctgctctgg agcccctggt ggacctgcca atcggcatca acatcaccag gttccagact 720 ctgcacgccc tgcacagatc ctacctgact cccggagact cttcatccgg ttggaccgct 780 ggcgctgccg cttactacgt gggttacctg cagccacgca ccttcctgct gaagtacaac 840 gaaaacggca ccatcactga cgccgtcgac tgcgctctgg acccactgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggaatctacc agacttcaaa cttccgcgtg 960 cagcctaccg aatccatcgt ccgtttccca aacatcacta acctgtgccc tttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga accgcaagcg tatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggagtgtcac ccactaagct gaacgacctg tgcttcacca acgtctacgc tgactccttc 1200 gtgatccgcg gtgacgaggt ccgtcagatc gctccaggcc agactggaaa catcgccgac 1260 tacaactaca agctgcctga cgacttcacc ggttgcgtca tcgcctggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtaca ggctgttcag aaagtcaaac 1380 ctgaagccct tcgagcgcga catcagcact gaaatctacc aggctggttc taccccatgc 1440 aacggtgtca agggcttcaa ctgctacttc cctctgcagt cctacggctt ccagcccact 1500 tacggtgtgg gctaccagcc ataccgtgtg gtcgtgctga gcttcgagct gctgcacgcc 1560 cctgctactg tgtgcggacc caagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggtctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cctttccagc agttcggtcg cgacatcgct gacaccactg acgccgtgcg tgaccctcag 1740 accctggaaa tcctggacat cactccctgc tcattcggag gtgtctccgt gatcactccc 1800 ggaaccaaca cttctaacca ggtcgctgtg ctgtaccagg gtgtgaactg caccgaagtc 1860 ccagtggcca tccacgctga ccagctgacc cctacttgga gggtgtactc caccggcagc 1920 aacgtcttcc agactagagc tggatgcctg atcggtgccg agcacgtcaa caacagctac 1980 gaatgcgaca tccctatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccccagcagg ctcagtctgt ggcctctcag tcaatcatcg cctacaccat gtcactgggt 2100 gtcgaaaact ccgtggctta ctctaacaac tcaatcgcca tccctaccaa cttcactatc 2160 agcgtgacca ctgagatcct gcccgtcagc atgaccaaga cttctgtgga ctgcactatg 2220 tacatctgcg gcgacagcac cgaatgctct aacctgctgc tgcagtacgg ttctttctgc 2280 acccagctga accgcgctct gactggcatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag accccaccta tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc agacccttcc aagcccagca agaggtcttt catcgaggac 2460 ctgctgttca acaaggtcac tctggccgac gctggtttca tcaagcagta cggcgactgc 2520 ctgggagaca tcgctgctcg cgacctgatc tgcgcccaga agttcaacgg cctgaccgtg 2580 ctgcccccac tgctgactga cgaaatgatc gctcagtaca ctagcgccct gctggctggc 2640 accatcactt caggttggac tttcggtgct ggtgctgctc tgcagatccc attcgctatg 2700 cagatggcct accgtttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caactcagcc atcggcaaga tccaggacag cctgagctct 2820 actgcctctg ctctgggaaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggcgccatca gctctgtgct gaacgacatc 2940 ctgtccaggc tggaccctcc cgaggctgaa gtccagatcg acaggctgat cactggaaga 3000 ctgcagtcac tgcagaccta cgtgactcag cagctgatcc gcgccgctga aatccgtgcc 3060 tccgctaacc tggccgctac caagatgagc gagtgcgtcc tgggccagtc taagagagtg 3120 gacttctgcg gcaagggata ccacctgatg tcattcccac agtccgcccc tcacggagtc 3180 gtgttcctgc acgtcaccta cgtgcccgct caggagaaga acttcaccac tgccccagct 3240 atctgccacg acggcaaggc tcacttccct cgcgaaggag tcttcgtgag caacggcacc 3300 cactggttcg tcactcagcg taacttctac gagccccaga tcatcaccac tgacaacact 3360 ttcgtgtctg gcaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgaccct 3420 ctgcagcccg agctggactc attcaaggaa gagctggaca agtacttcaa gaaccacacc 3480 tcccctgacg tcgacctggg tgacatctca ggcatcaacg cctccgtcgt gaacatccag 3540 aaggagatcg accgcctgaa cgaagtggct aagaacctga acgaaagcct gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggccat ggtacatctg gctgggattc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggttg ctgcagctgc ggctcttgct gcaagttcga cgaggacgac 3780 tctgaacctg tcctgaaggg agtgaagctg cactacacct aa 3822 <![CDATA[<210> 132]]> <![CDATA[<211> 1259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 132]]> 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 20 25 30 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 Ala 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 His 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 Asn 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 435 440 445 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 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys 785 790 795 800 Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp 805 810 815 Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala 820 825 830 Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro 835 840 845 Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu 850 855 860 Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu 865 870 875 880 Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly 885 890 895 Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln 900 905 910 Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala 915 920 925 Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala 930 935 940 Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser 945 950 955 960 Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu 965 970 975 Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr 980 985 990 Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 995 1000 1005 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser 1010 1015 1020 Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe 1025 1030 1035 Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 1040 1045 1050 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys 1055 1060 1065 His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser 1070 1075 1080 Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro 1085 1090 1095 Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp 1100 1105 1110 Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln 1115 1120 1125 Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys 1130 1135 1140 Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile 1145 1150 1155 Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn 1160 1165 1170 Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu 1175 1180 1185 Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp 1190 1195 1200 Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile 1205 1210 1215 Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys 1220 1225 1230 Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu 1235 1240 1245 Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 133]]> <![CDATA[<211> 1258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 133]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 435 440 445 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Gly Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 785 790 795 800 Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 805 810 815 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 820 825 830 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 835 840 845 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 850 855 860 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln 865 870 875 880 Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 885 890 895 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 900 905 910 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser 915 920 925 Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu 930 935 940 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 945 950 955 960 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 965 970 975 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 980 985 990 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 995 1000 1005 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1010 1015 1020 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1025 1030 1035 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1040 1045 1050 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1055 1060 1065 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1070 1075 1080 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1085 1090 1095 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1100 1105 1110 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1115 1120 1125 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1130 1135 1140 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1145 1150 1155 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1160 1165 1170 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1175 1180 1185 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1190 1195 1200 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1205 1210 1215 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1220 1225 1230 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1235 1240 1245 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 134]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 134]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Gly Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 135]]> <![CDATA[<211> 3813]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 135]]> Ala Thr Gly Thr Thr Cys Gly Thr Cys Thr Thr Cys Cys Thr Gly Gly 1 5 10 15 Thr Gly Cys Thr Gly Cys Thr Gly Cys Cys Thr Cys Thr Gly Gly Thr 20 25 30 Gly Thr Cys Cys Ala Gly Cys Cys Ala Gly Thr Gly Cys Gly Thr Gly 35 40 45 Ala Ala Cys Cys Thr Gly Ala Cys Cys Ala Cys Thr Ala Gly Gly Ala 50 55 60 Cys Thr Cys Ala Gly Cys Thr Gly Cys Cys Thr Cys Cys Cys Gly Cys 65 70 75 80 Thr Thr Ala Cys Ala Cys Cys Ala Ala Cys Ala Gly Cys Thr Thr Cys 85 90 95 Ala Cys Thr Ala Gly Gly Gly Gly Thr Gly Thr Cys Thr Ala Cys Thr 100 105 110 Ala Cys Cys Cys Thr Gly Ala Cys Ala Ala Gly Gly Thr Cys Thr Thr 115 120 125 Cys Cys Gly Cys Thr Cys Cys Thr Cys Ala Gly Thr Gly Cys Thr Gly 130 135 140 Cys Ala Cys Thr Cys Thr Ala Cys Thr Cys Ala Gly Gly Ala Cys Cys 145 150 155 160 Thr Gly Thr Thr Cys Cys Thr Gly Cys Cys Cys Thr Thr Cys Thr Thr 165 170 175 Cys Thr Cys Ala Ala Ala Cys Gly Thr Gly Ala Cys Cys Thr Gly Gly 180 185 190 Thr Thr Cys Cys Ala Cys Gly Cys Cys Ala Thr Cys Thr Cys Cys Gly 195 200 205 Gly Cys Ala Cys Cys Ala Ala Cys Gly Gly Cys Ala Cys Thr Ala Ala 210 215 220 Gly Ala Gly Gly Thr Thr Cys Gly Ala Cys Ala Ala Cys Cys Cys Cys 225 230 235 240 Gly Thr Gly Cys Thr Gly Cys Cys Ala Thr Thr Cys Ala Ala Cys Gly 245 250 255 Ala Cys Gly Gly Cys Gly Thr Cys Thr Ala Cys Thr Thr Cys Gly Cys 260 265 270 Thr Thr Cys Ala Ala Cys Cys Gly Ala Gly Ala Ala Gly Thr Cys Cys 275 280 285 Ala Ala Cys Ala Thr Cys Ala Thr Cys Ala Gly Ala Gly Gly Ala Thr 290 295 300 Gly Gly Ala Thr Cys Thr Thr Cys Gly Gly Cys Ala Cys Cys Ala Cys 305 310 315 320 Thr Cys Thr Gly Gly Ala Cys Ala Gly Cys Ala Ala Gly Ala Cys Thr 325 330 335 Cys Ala Gly Thr Cys Thr Cys Thr Gly Cys Thr Gly Ala Thr Cys Gly 340 345 350 Thr Cys Ala Ala Cys Ala Ala Cys Gly Cys Cys Ala Cys Cys Ala Ala 355 360 365 Cys Gly Thr Gly Gly Thr Cys Ala Thr Cys Ala Ala Gly Gly Thr Gly 370 375 380 Thr Gly Cys Gly Ala Ala Thr Thr Cys Cys Ala Gly Thr Thr Cys Thr 385 390 395 400 Gly Cys Ala Ala Cys Gly Ala Cys Cys Cys Ala Thr Thr Cys Cys Thr 405 410 415 Gly Gly Gly Thr Gly Thr Gly Thr Ala Cys Cys Ala Cys Ala Ala Gly 420 425 430 Ala Ala Cys Ala Ala Cys Ala Ala Gly Thr Cys Ala Thr Gly Gly Ala 435 440 445 Thr Gly Gly Ala Gly Thr Cys Cys Gly Ala Ala Thr Thr Cys Cys Gly 450 455 460 Cys Gly Thr Cys Thr Ala Cys Thr Cys Cys Ala Gly Cys Gly Cys Thr 465 470 475 480 Ala Ala Cys Ala Ala Cys Thr Gly Cys Ala Cys Thr Thr Thr Cys Gly 485 490 495 Ala Gly Thr Ala Cys Gly Thr Gly Ala Gly Cys Cys Ala Gly Cys Cys 500 505 510 Thr Thr Thr Cys Cys Thr Gly Ala Thr Gly Gly Ala Cys Cys Thr Gly 515 520 525 Gly Ala Ala Gly Gly Ala Ala Ala Gly Cys Ala Gly Gly Gly Thr Ala 530 535 540 Ala Cys Thr Thr Cys Ala Ala Gly Ala Ala Cys Cys Thr Gly Cys Gly 545 550 555 560 Cys Gly Ala Gly Thr Thr Cys Gly Thr Gly Thr Thr Cys Ala Ala Gly 565 570 575 Ala Ala Cys Ala Thr Cys Gly Ala Cys Gly Gly Ala Thr Ala Cys Thr 580 585 590 Thr Cys Ala Ala Gly Ala Thr Thr Thr Ala Cys Ala Gly Cys Ala Ala 595 600 605 Gly Cys Ala Cys Ala Cys Cys Cys Cys Cys Ala Thr Cys Ala Ala Cys 610 615 620 Cys Thr Gly Gly Thr Cys Cys Gly Thr Gly Ala Cys Cys Thr Gly Cys 625 630 635 640 Cys Ala Cys Ala Gly Gly Gly Thr Thr Thr Cys Thr Cys Thr Gly Cys 645 650 655 Thr Cys Thr Gly Gly Ala Gly Cys Cys Cys Cys Thr Gly Gly Thr Gly 660 665 670 Gly Ala Cys Cys Thr Gly Cys Cys Ala Ala Thr Cys Gly Gly Cys Ala 675 680 685 Thr Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Ala Gly Gly Thr Thr 690 695 700 Cys Cys Ala Gly Ala Cys Thr Cys Thr Gly Cys Thr Gly Gly Cys Thr 705 710 715 720 Cys Thr Gly Cys Ala Cys Cys Gly Cys Thr Cys Cys Thr Ala Cys Cys 725 730 735 Thr Gly Ala Cys Thr Cys Cys Ala Gly Gly Thr Gly Ala Cys Thr Cys 740 745 750 Ala Thr Cys Thr Thr Cys Thr Gly Gly Ala Thr Gly Gly Ala Cys Thr 755 760 765 Gly Cys Thr Gly Gly Ala Gly Cys Thr Gly Cys Thr Gly Cys Thr Thr 770 775 780 Ala Cys Thr Ala Cys Gly Thr Gly Gly Gly Thr Thr Ala Cys Cys Thr 785 790 795 800 Gly Cys Ala Gly Cys Cys Thr Cys Gly Cys Ala Cys Cys Thr Thr Cys 805 810 815 Cys Thr Gly Cys Thr Gly Ala Ala Gly Thr Ala Cys Ala Ala Cys Gly 820 825 830 Ala Ala Ala Ala Cys Gly Gly Cys Ala Cys Cys Ala Thr Cys Ala Cys 835 840 845 Thr Gly Ala Cys Gly Cys Cys Gly Thr Cys Gly Ala Cys Thr Gly Cys 850 855 860 Gly Cys Thr Cys Thr Gly Gly Ala Cys Cys Cys Thr Cys Thr Gly Thr 865 870 875 880 Cys Ala Gly Ala Ala Ala Cys Cys Ala Ala Gly Thr Gly Cys Ala Cys 885 890 895 Thr Cys Thr Gly Ala Ala Gly Thr Cys Cys Thr Thr Cys Ala Cys Cys 900 905 910 Gly Thr Gly Gly Ala Gly Ala Ala Gly Gly Gly Thr Ala Thr Cys Thr 915 920 925 Ala Cys Cys Ala Gly Ala Cys Thr Ala Gly 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1935 Cys Thr Gly Ala Thr Cys Gly Gly Cys Gly Cys Cys Gly Ala Gly 1940 1945 1950 Cys Ala Cys Gly Thr Gly Ala Ala Cys Ala Ala Cys Ala Gly Cys 1955 1960 1965 Thr Ala Cys Gly Ala Ala Thr Gly Cys Gly Ala Cys Ala Thr Cys 1970 1975 1980 Cys Cys Ala Ala Thr Cys Gly Gly Cys Gly Cys Thr Gly Gly Ala 1985 1990 1995 Ala Thr Cys Thr Gly Cys Gly Cys Cys Thr Cys Thr Thr Ala Cys 2000 2005 2010 Cys Ala Gly Ala Cys Cys Cys Ala Gly Ala Cys Thr Ala Ala Cys 2015 2020 2025 Ala Gly Cys Cys Ala Cys Cys Ala Gly Cys Ala Gly Gly Cys Thr 2030 2035 2040 Cys Ala Gly Thr Cys Thr Gly Thr Cys Gly Cys Cys Thr Cys Thr 2045 2050 2055 Cys Ala Gly Thr Cys Ala Ala Thr Cys Ala Thr Cys Gly Cys Thr 2060 2065 2070 Thr Ala Cys Ala Cys Thr Ala Thr Gly Thr Cys Ala Cys Thr Gly 2075 2080 2085 Gly Gly Cys Gly Cys Thr Gly Ala Ala Ala Ala Cys Thr Cys Cys 2090 2095 2100 Gly Thr Gly Gly Cys Cys Thr Ala Cys Thr Cys Thr Ala Ala Cys 2105 2110 2115 Ala Ala Cys Thr Cys Ala Ala Thr Cys Gly Cys Cys Ala Thr Cys 2120 2125 2130 Cys Cys Thr Ala Thr 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2535 Ala Thr Cys Thr Gly Cys Gly Cys Thr Cys Ala Gly Ala Ala Gly 2540 2545 2550 Thr Thr Cys Ala Ala Cys Gly Gly Ala Cys Thr Gly Ala Cys Cys 2555 2560 2565 Gly Thr Gly Cys Thr Gly Cys Cys Cys Cys Cys Ala Cys Thr Gly 2570 2575 2580 Cys Thr Gly Ala Cys Thr Gly Ala Cys Gly Ala Ala Ala Thr Gly 2585 2590 2595 Ala Thr Cys Gly Cys Cys Cys Ala Gly Thr Ala Cys Ala Cys Thr 2600 2605 2610 Thr Cys Ala Gly Cys Cys Cys Thr Gly Cys Thr Gly Gly Cys Thr 2615 2620 2625 Gly Gly Ala Ala Cys Cys Ala Thr Cys Ala Cys Thr Thr Cys Thr 2630 2635 2640 Gly Gly Thr Thr Gly Gly Ala Cys Cys Thr Thr Cys Gly Gly Thr 2645 2650 2655 Gly Cys Thr Gly Gly Thr Gly Cys Thr Gly Cys Thr Cys Thr Gly 2660 2665 2670 Cys Ala Gly Ala Thr Cys Cys Cys Thr Thr Thr Cys Gly Cys Thr 2675 2680 2685 Ala Thr Gly Cys Ala Gly Ala Thr Gly Gly Cys Cys Thr Ala Cys 2690 2695 2700 Cys Gly Thr Thr Thr Cys Ala Ala Cys Gly Gly Ala Ala Thr Cys 2705 2710 2715 Gly Gly Thr Gly Thr Cys Ala Cys Cys Cys Ala Gly Ala Ala Cys 2720 2725 2730 Gly Thr Gly Cys Thr 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3135 Ala Thr Gly Thr Cys Ala Thr Thr Cys Cys Cys Ala Cys Ala Gly 3140 3145 3150 Thr Cys Cys Gly Cys Thr Cys Cys Thr Cys Ala Cys Gly Gly Thr 3155 3160 3165 Gly Thr Cys Gly Thr Gly Thr Thr Cys Cys Thr Gly Cys Ala Cys 3170 3175 3180 Gly Thr Cys Ala Cys Cys Thr Ala Cys Gly Thr Gly Cys Cys Cys 3185 3190 3195 Gly Cys Cys Cys Ala Gly Gly Ala Gly Ala Ala Gly Ala Ala Cys 3200 3205 3210 Thr Thr Cys Ala Cys Cys Ala Cys Thr Gly Cys Cys Cys Cys Ala 3215 3220 3225 Gly Cys Thr Ala Thr Cys Thr Gly Cys Cys Ala Cys Gly Ala Cys 3230 3235 3240 Gly Gly Cys Ala Ala Gly Gly Cys Thr Cys Ala Cys Thr Thr Cys 3245 3250 3255 Cys Cys Cys Cys Gly Cys Gly Ala Ala Gly Gly Thr Gly Thr Cys 3260 3265 3270 Thr Thr Cys Gly Thr Gly Thr Cys Ala Ala Ala Cys Gly Gly Cys 3275 3280 3285 Ala Cys Cys Cys Ala Cys Thr Gly Gly Thr Thr Cys Gly Thr Cys 3290 3295 3300 Ala Cys Thr Cys Ala Gly Cys Gly Thr Ala Ala Cys Thr Thr Cys 3305 3310 3315 Thr Ala Cys Gly Ala Gly Cys Cys Ala Cys Ala Gly Ala Thr Cys 3320 3325 3330 Ala Thr Cys Ala Cys Cys Ala Cys Thr Cys Ala Cys Ala Ala Cys 3335 3340 3345 Ala Cys Thr Thr Thr Cys Gly Thr Gly Thr Cys Cys Gly Gly Ala 3350 3355 3360 Ala Ala Cys Thr Gly Cys Gly Ala Cys Gly Thr Gly Gly Thr Cys 3365 3370 3375 Ala Thr Cys Gly Gly Thr Ala Thr Cys Gly Thr Cys Ala Ala Cys 3380 3385 3390 Ala Ala Cys Ala Cys Cys Gly Thr Gly Thr Ala Cys Gly Ala Cys 3395 3400 3405 Cys Cys Thr Cys Thr Gly Cys Ala Gly Cys Cys Cys Gly Ala Gly 3410 3415 3420 Cys Thr Gly Gly Ala Cys Thr Cys Ala Thr Thr Cys Ala Ala Gly 3425 3430 3435 Gly Ala Ala Gly Ala Gly Cys Thr Gly Gly Ala Cys Ala Ala Gly 3440 3445 3450 Thr Ala Cys Thr Thr Cys Ala Ala Gly Ala Ala Cys Cys Ala Cys 3455 3460 3465 Ala Cys Cys Thr Cys Cys Cys Cys Thr Gly Ala Cys Gly Thr Cys 3470 3475 3480 Gly Ala Cys Cys Thr Gly Gly Gly Cys Gly Ala Cys Ala Thr Cys 3485 3490 3495 Thr Cys Ala Gly Gly Ala Ala Thr Cys Ala Ala Cys Gly Cys Thr 3500 3505 3510 Thr Cys Cys Gly Thr Cys Gly Thr Gly Ala Ala Cys Ala Thr Cys 3515 3520 3525 Cys Ala Gly Ala Ala Gly Gly Ala Gly Ala Thr Cys Gly Ala Cys 3530 3535 3540 Cys Gly Cys Cys Thr Gly Ala Ala Cys Gly Ala Ala Gly Thr Gly 3545 3550 3555 Gly Cys Cys Ala Ala Gly Ala Ala Cys Cys Thr Gly Ala Ala Cys 3560 3565 3570 Gly Ala Ala Thr Cys Ala Cys Thr Gly Ala Thr Cys Gly Ala Cys 3575 3580 3585 Cys Thr Gly Cys Ala Gly Gly Ala Gly Cys Thr Gly Gly Gly Cys 3590 3595 3600 Ala Ala Gly Thr Ala Cys Gly Ala Ala Cys Ala Gly Thr Ala Cys 3605 3610 3615 Ala Thr Cys Ala Ala Gly Thr Gly Gly Cys Cys Thr Thr Gly Gly 3620 3625 3630 Thr Ala Cys Ala Thr Cys Thr Gly Gly Cys Thr Gly Gly Gly Thr 3635 3640 3645 Thr Thr Cys Ala Thr Cys Gly Cys Thr Gly Gly Cys Cys Thr Cys 3650 3655 3660 Ala Thr Cys Gly Cys Thr Ala Thr Cys Gly Thr Gly Ala Thr Gly 3665 3670 3675 Gly Thr Gly Ala Cys Cys Ala Thr Cys Ala Thr Gly Cys Thr Gly 3680 3685 3690 Thr Gly Cys Thr Gly Cys Ala Thr Gly Ala Cys Thr Thr Cys Ala 3695 3700 3705 Thr Gly Cys Thr Gly Cys Thr Cys Cys Thr Gly Cys Cys Thr Gly 3710 3715 3720 Ala Ala Gly Gly Gly Cys Thr Gly Cys Thr Gly Cys Ala Gly Cys 3725 3730 3735 Thr Gly Cys Gly Gly Ala Thr Cys Thr Thr Gly Cys Thr Gly Cys 3740 3745 3750 Ala Ala Gly Thr Thr Cys Gly Ala Cys Gly Ala Gly Gly Ala Cys 3755 3760 3765 Gly Ala Cys Thr Cys Cys Gly Ala Ala Cys Cys Cys Gly Thr Cys 3770 3775 3780 Cys Thr Gly Ala Ala Gly Gly Gly Ala Gly Thr Gly Ala Ala Gly 3785 3790 3795 Cys Thr Gly Cys Ala Cys Thr Ala Cys Ala Cys Cys Thr Ala Ala 3800 3805 3810 <![CDATA[<210> 136]]> <![CDATA[<211> 1270]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 136]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro 65 70 75 80 Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser 85 90 95 Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr 100 105 110 Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val 115 120 125 Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr His Lys 130 135 140 Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala 145 150 155 160 Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu 165 170 175 Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys 180 185 190 Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn 195 200 205 Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val 210 215 220 Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala 225 230 235 240 Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr 245 250 255 Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe 260 265 270 Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys 275 280 285 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr 290 295 300 Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr 305 310 315 320 Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 325 330 335 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 340 345 350 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 355 360 365 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 370 375 380 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 385 390 395 400 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 405 410 415 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 420 425 430 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 435 440 445 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 450 455 460 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 465 470 475 480 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 485 490 495 Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 500 505 510 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 515 520 525 Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr 530 535 540 Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln 545 550 555 560 Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val Arg Asp Pro 565 570 575 Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val 580 585 590 Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu 595 600 605 Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp 610 615 620 Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe 625 630 635 640 Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser 645 650 655 Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln 660 665 670 Thr Gln Thr Asn Ser His Gln Gln Ala Gln Ser Val Ala Ser Gln Ser 675 680 685 Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr 690 695 700 Ser Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val Thr 705 710 715 720 Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr 725 730 735 Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln 740 745 750 Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala 755 760 765 Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln 770 775 780 Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser 785 790 795 800 Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu 805 810 815 Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys 820 825 830 Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys 835 840 845 Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp 850 855 860 Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr 865 870 875 880 Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala 885 890 895 Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val 900 905 910 Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile 915 920 925 Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys 930 935 940 Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val 945 950 955 960 Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp 965 970 975 Ile Leu Ala Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg 980 985 990 Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln 995 1000 1005 Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala 1010 1015 1020 Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp 1025 1030 1035 Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 1040 1045 1050 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln 1055 1060 1065 Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 1070 1075 1080 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His 1085 1090 1095 Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr 1100 1105 1110 Thr His Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 1115 1120 1125 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp 1130 1135 1140 Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser 1145 1150 1155 Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val 1160 1165 1170 Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys 1175 1180 1185 Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr 1190 1195 1200 Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile 1205 1210 1215 Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys 1220 1225 1230 Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly 1235 1240 1245 Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys 1250 1255 1260 Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 137]]> <![CDATA[<211> 1268]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 137]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro 65 70 75 80 Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser 85 90 95 Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr 100 105 110 Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val 115 120 125 Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr His Lys 130 135 140 Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala 145 150 155 160 Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu 165 170 175 Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys 180 185 190 Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn 195 200 205 Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val 210 215 220 Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala 225 230 235 240 Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr 245 250 255 Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe 260 265 270 Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys 275 280 285 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr 290 295 300 Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr 305 310 315 320 Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 325 330 335 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 340 345 350 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 355 360 365 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 370 375 380 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 385 390 395 400 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 405 410 415 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 420 425 430 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 435 440 445 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 450 455 460 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 465 470 475 480 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 485 490 495 Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 500 505 510 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 515 520 525 Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr 530 535 540 Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln 545 550 555 560 Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val Arg Asp Pro 565 570 575 Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val 580 585 590 Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu 595 600 605 Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp 610 615 620 Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe 625 630 635 640 Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser 645 650 655 Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln 660 665 670 Thr Gln Thr Asn Ser His Gly Gly Ser Val Ala Ser Gln Ser Ile Ile 675 680 685 Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn 690 695 700 Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val Thr Thr Glu 705 710 715 720 Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr 725 730 735 Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly 740 745 750 Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu 755 760 765 Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr 770 775 780 Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile 785 790 795 800 Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu 805 810 815 Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr 820 825 830 Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln 835 840 845 Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met 850 855 860 Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly 865 870 875 880 Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln 885 890 895 Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr 900 905 910 Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys 915 920 925 Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln 930 935 940 Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln 945 950 955 960 Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu 965 970 975 Ala Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile 980 985 990 Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile 995 1000 1005 Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys 1010 1015 1020 Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys 1025 1030 1035 Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His 1040 1045 1050 Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys 1055 1060 1065 Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His 1070 1075 1080 Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe 1085 1090 1095 Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr His 1100 1105 1110 Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val 1115 1120 1125 Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe 1130 1135 1140 Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp 1145 1150 1155 Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn 1160 1165 1170 Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu 1175 1180 1185 Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln 1190 1195 1200 Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly 1205 1210 1215 Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr 1220 1225 1230 Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys 1235 1240 1245 Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val 1250 1255 1260 Lys Leu His Tyr Thr 1265 <![CDATA[<210> 138]]> <![CDATA[<211> 1255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 138]]> 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 20 25 30 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 Ser Gly Thr Asn Gly Thr Lys Arg Phe 50 55 60 Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr 65 70 75 80 Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp 85 90 95 Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val 100 105 110 Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val 115 120 125 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 130 135 140 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 145 150 155 160 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 165 170 175 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 180 185 190 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 195 200 205 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 210 215 220 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 225 230 235 240 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 245 250 255 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 260 265 270 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 275 280 285 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 290 295 300 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 305 310 315 320 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 325 330 335 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 340 345 350 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 355 360 365 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 370 375 380 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 385 390 395 400 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 405 410 415 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 420 425 430 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 435 440 445 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 450 455 460 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 465 470 475 480 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 485 490 495 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 500 505 510 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 515 520 525 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 530 535 540 Pro Phe Gln Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val 545 550 555 560 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 565 570 575 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 580 585 590 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 595 600 605 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 610 615 620 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 625 630 635 640 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 645 650 655 Ser Tyr Gln Thr Gln Thr Asn Ser His Gly Gly Ser Val Ala Ser Gln 660 665 670 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 675 680 685 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val 690 695 700 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 705 710 715 720 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 725 730 735 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 740 745 750 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 755 760 765 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 770 775 780 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 785 790 795 800 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 805 810 815 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 820 825 830 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 835 840 845 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 850 855 860 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 865 870 875 880 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 885 890 895 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 900 905 910 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 915 920 925 Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 930 935 940 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 945 950 955 960 Asp Ile Leu Ala Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 965 970 975 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 980 985 990 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala 995 1000 1005 Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp 1010 1015 1020 Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 1025 1030 1035 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln 1040 1045 1050 Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 1055 1060 1065 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His 1070 1075 1080 Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr 1085 1090 1095 Thr His Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 1100 1105 1110 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp 1115 1120 1125 Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser 1130 1135 1140 Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val 1145 1150 1155 Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys 1160 1165 1170 Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr 1175 1180 1185 Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile 1190 1195 1200 Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys 1205 1210 1215 Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly 1220 1225 1230 Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys 1235 1240 1245 Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 139]]> <![CDATA[<211> 3807]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 139]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac agcttcacta ggggtgtcta ctaccctgac 120 aaggtcttcc gctcctcagt gctgcactct actcaggacc tgttcctgcc cttcttctca 180 aacgtgacct ggttccacgc catctccggc accaacggca ctaagaggtt cgacaacccc 240 gtgctgccat tcaacgacgg cgtctacttc gcttcaaccg agaagtccaa catcatcaga 300 ggatggatct tcggcaccac tctggacagc aagactcagt ctctgctgat cgtcaacaac 360 gccaccaacg tggtcatcaa ggtgtgcgaa ttccagttct gcaacgaccc attcctgggt 420 gtgtaccaca agaacaacaa gtcatggatg gagtccgaat tccgcgtcta ctccagcgct 480 aacaactgca ctttcgagta cgtgagccag cctttcctga tggacctgga aggaaagcag 540 ggtaacttca agaacctgcg cgagttcgtg ttcaagaaca tcgacggata cttcaagatt 600 tacagcaagc acacccccat caacctggtc cgtgacctgc cacagggttt ctctgctctg 660 gagcccctgg tggacctgcc aatcggcatc aacatcacca ggttccagac tctgctggct 720 ctgcaccgct cctacctgac tccaggtgac tcatcttctg gatggactgc tggagctgct 780 gcttactacg tgggttacct gcagcctcgc accttcctgc tgaagtacaa cgaaaacggc 840 accatcactg acgccgtcga ctgcgctctg gaccctctgt cagaaaccaa gtgcactctg 900 aagtccttca ccgtggagaa gggtatctac cagactagca acttccgcgt gcagcccacc 960 gaatctatcg tccgtttccc aaacatcact aacctgtgcc ctttcggcga ggtcttcaac 1020 gccacccgct tcgcttccgt gtacgcctgg aaccgcaagc gtatctcaaa ctgcgtcgct 1080 gactactccg tgctgtacaa ctcagcctcc ttcagcacct tcaagtgcta cggtgtgtca 1140 cccactaagc tgaacgacct gtgcttcacc aacgtctacg ccgactcctt cgtgatccgc 1200 ggcgacgagg tccgtcagat cgctccaggc cagactggaa agatcgccga ctacaactac 1260 aagctgcctg acgacttcac cggctgcgtc atcgcttgga acagcaacaa cctggactct 1320 aaagtgggtg gcaactacaa ctacctgtac aggctgttca gaaagagcaa cctgaagccc 1380 ttcgagcgcg acatcagcac tgaaatctac caggctggct ctaccccatg caacggtgtc 1440 gagggcttca actgctactt ccctctgcag tcttacggat tccagcccac ttacggtgtg 1500 ggctaccagc cataccgtgt ggtcgtgctg agcttcgaac tgctgcacgc ccctgctact 1560 gtgtgcggac ccaagaagtc taccaacctg gtcaagaaca agtgcgtgaa cttcaacttc 1620 aacggtctga ccggaactgg tgtcctgacc gagagcaaca agaagttcct gcccttccag 1680 cagttcggtc gcgacatcga cgacaccact gacgccgtgc gtgaccctca gaccctggaa 1740 atcctggaca tcactccctg ctcattcgga ggtgtctccg tgatcactcc aggaaccaac 1800 acttctaacc aggtcgctgt gctgtaccag ggtgtcaact gcaccgaggt cccagtggcc 1860 atccacgctg accagctgac ccctacttgg agggtgtact ccaccggcag caacgtgttc 1920 cagactagag ctggttgcct gatcggcgcc gagcacgtga acaacagcta cgaatgcgac 1980 atcccaatcg gcgctggaat ctgcgcctct taccagaccc agactaacag ccacggtggt 2040 tctgtcgcct ctcagtcaat catcgcttac actatgtcac tgggcgctga aaactccgtg 2100 gcctactcta acaactcaat cgccatccct atcaacttca ccatctcagt gaccactgag 2160 atcctgcccg tcagcatgac caagacttct gtggactgca ctatgtacat ctgcggagac 2220 agcaccgaat gctctaacct gctgctgcag tacggctcct tctgcaccca gctgaaccgc 2280 gctctgactg gaatcgccgt ggagcaggac aagaacactc aggaagtctt cgctcaggtg 2340 aagcaaatct acaagacccc acctatcaag gacttcggcg gattcaactt ctcccagatc 2400 ctgccagacc cttccaagcc aagcaagagg tctttcatcg aggacctgct gttcaacaag 2460 gtcaccctgg ccgacgctgg cttcatcaag cagtacggag actgcctggg tgacatcgcc 2520 gctcgcgacc tgatctgcgc tcagaagttc aacggactga ccgtgctgcc cccactgctg 2580 actgacgaaa tgatcgccca gtacacttca gccctgctgg ctggaaccat cacttctggt 2640 tggaccttcg gtgctggtgc tgctctgcag atccctttcg ctatgcagat ggcctaccgt 2700 ttcaacggaa tcggtgtcac ccagaacgtg ctgtacgaga accagaagct gatcgctaac 2760 cagttcaact ccgccatcgg caagatccag gacagcctga gctctactgc ctctgctctg 2820 ggaaagctgc aggacgtcgt gaaccagaac gcccaggctc tgaacaccct ggtcaagcag 2880 ctgtcatcca acttcggagc catcagctct gtgctgaacg acatcctcgc taggctggac 2940 cctcccgagg ctgaagtcca gatcgacagg ctgatcactg gtagactgca gtcactgcag 3000 acctacgtga ctcagcagct gatccgcgcc gctgaaatcc gtgcctccgc taacctggcc 3060 gctaccaaga tgagcgagtg cgtcctggga cagtctaaga gagtggactt ctgcggcaag 3120 ggataccacc tgatgtcatt cccacagtcc gctcctcacg gtgtcgtgtt cctgcacgtc 3180 acctacgtgc ccgcccagga gaagaacttc accactgccc cagctatctg ccacgacggc 3240 aaggctcact tcccccgcga aggtgtcttc gtgtcaaacg gcacccactg gttcgtcact 3300 cagcgtaact tctacgagcc acagatcatc accactcaca acactttcgt gtccggaaac 3360 tgcgacgtgg tcatcggtat cgtcaacaac accgtgtacg accctctgca gcccgagctg 3420 gactcattca aggaagagct ggacaagtac ttcaagaacc acacctcccc tgacgtcgac 3480 ctgggcgaca tctcaggaat caacgcttcc gtcgtgaaca tccagaagga gatcgaccgc 3540 ctgaacgaag tggccaagaa cctgaacgaa tcactgatcg acctgcagga gctgggcaag 3600 tacgaacagt acatcaagtg gccttggtac atctggctgg gtttcatcgc tggcctcatc 3660 gctatcgtga tggtgaccat catgctgtgc tgcatgactt catgctgctc ctgcctgaag 3720 ggctgctgca gctgcggatc ttgctgcaag ttcgacgagg acgactccga acccgtcctg 3780 aagggagtga agctgcacta cacctaa 3807 <![CDATA[<210> 140]]> <![CDATA[<211> 1270]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 140]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu His Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Gly Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn Phe Ser 785 790 795 800 Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu 805 810 815 Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys 820 825 830 Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys 835 840 845 Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp 850 855 860 Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr 865 870 875 880 Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala 885 890 895 Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val 900 905 910 Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile 915 920 925 Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys 930 935 940 Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val 945 950 955 960 Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp 965 970 975 Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg 980 985 990 Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln 995 1000 1005 Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala 1010 1015 1020 Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp 1025 1030 1035 Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 1040 1045 1050 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln 1055 1060 1065 Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys 1070 1075 1080 Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His 1085 1090 1095 Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr 1100 1105 1110 Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 1115 1120 1125 Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp 1130 1135 1140 Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser 1145 1150 1155 Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val 1160 1165 1170 Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys 1175 1180 1185 Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr 1190 1195 1200 Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile 1205 1210 1215 Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys 1220 1225 1230 Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly 1235 1240 1245 Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys 1250 1255 1260 Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 141]]> <![CDATA[<211> 1257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 141]]> 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 20 25 30 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 Ala 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 His 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 Asn 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 435 440 445 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 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Gly Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 785 790 795 800 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 805 810 815 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 820 825 830 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 835 840 845 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 850 855 860 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 865 870 875 880 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 885 890 895 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 900 905 910 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 915 920 925 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 930 935 940 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 945 950 955 960 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 965 970 975 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 980 985 990 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 995 1000 1005 Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg 1010 1015 1020 Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln 1025 1030 1035 Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro 1040 1045 1050 Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp 1055 1060 1065 Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly 1070 1075 1080 Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile 1085 1090 1095 Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val 1100 1105 1110 Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu 1115 1120 1125 Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His 1130 1135 1140 Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala 1145 1150 1155 Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val 1160 1165 1170 Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly 1175 1180 1185 Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly 1190 1195 1200 Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu 1205 1210 1215 Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser 1220 1225 1230 Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 1235 1240 1245 Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 142]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 142]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cctgaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcacta ggggtgtgta ctacccagac 120 aaggtcttcc gctcctcagt gctgcactca actcaggacc tgttcctgcc tttcttctcc 180 aacgtcacct ggttccacgc tatccacgtg tccggcacca acggcactaa gaggttcgcc 240 aaccccgtgc tgccattcaa cgacggagtc tacttcgctt caaccgagaa gtccaacatc 300 atcagaggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcta ccaacgtggt catcaaggtg tgcgaattcc agttctgtaa cgaccccttc 420 ctgggtgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc cattcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgcgc gagttcgtgt tcaagaacat cgacggctac 600 ttcaagattt acagcaagca cacccccatc aacctggtcc gtggcctgcc acagggattc 660 tctgctctgg agcccctggt ggacctgcca atcggcatca acatcaccag gttccagact 720 ctgcacgccc tgcacagatc ctacctgact cccggagact cttcatccgg ttggaccgct 780 ggcgctgccg cttactacgt gggttacctg cagccacgca ccttcctgct gaagtacaac 840 gaaaacggca ccatcactga cgccgtcgac tgcgctctgg acccactgtc agaaaccaag 900 tgcactctga agtccttcac cgtggagaag ggaatctacc agacttcaaa cttccgcgtg 960 cagcctaccg aatccatcgt ccgtttccca aacatcacta acctgtgccc tttcggagag 1020 gtcttcaacg ccacccgctt cgcttccgtg tacgcctgga accgcaagcg tatctcaaac 1080 tgcgtcgctg actactccgt gctgtacaac tcagcctcct tcagcacctt caagtgctac 1140 ggagtgtcac ccactaagct gaacgacctg tgcttcacca acgtctacgc tgactccttc 1200 gtgatccgcg gtgacgaggt ccgtcagatc gctccaggcc agactggaaa catcgccgac 1260 tacaactaca agctgcctga cgacttcacc ggttgcgtca tcgcctggaa cagcaacaac 1320 ctggactcta aagtgggtgg caactacaac tacctgtaca ggctgttcag aaagtcaaac 1380 ctgaagccct tcgagcgcga catcagcact gaaatctacc aggctggttc taccccatgc 1440 aacggtgtca agggcttcaa ctgctacttc cctctgcagt cctacggctt ccagcccact 1500 tacggtgtgg gctaccagcc ataccgtgtg gtcgtgctga gcttcgagct gctgcacgcc 1560 cctgctactg tgtgcggacc caagaagtct accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggtctgac cggaactggt gtcctgaccg agagcaacaa gaagttcctg 1680 cctttccagc agttcggtcg cgacatcgct gacaccactg acgccgtgcg tgaccctcag 1740 accctggaaa tcctggacat cactccctgc tcattcggag gtgtctccgt gatcactccc 1800 ggaaccaaca cttctaacca ggtcgctgtg ctgtaccagg gtgtgaactg caccgaagtc 1860 ccagtggcca tccacgctga ccagctgacc cctacttgga gggtgtactc caccggcagc 1920 aacgtcttcc agactagagc tggatgcctg atcggtgccg agcacgtcaa caacagctac 1980 gaatgcgaca tccctatcgg cgctggaatc tgcgcctctt accagaccca gactaacagc 2040 ccaggtggtt ctgtggcctc tcagtcaatc atcgcctaca ccatgtcact gggtgtcgaa 2100 aactccgtgg cttactctaa caactcaatc gccatcccta ccaacttcac tatcagcgtg 2160 accactgaga tcctgcccgt cagcatgacc aagacttctg tggactgcac tatgtacatc 2220 tgcggcgaca gcaccgaatg ctctaacctg ctgctgcagt acggttcttt ctgcacccag 2280 ctgaaccgcg ctctgactgg catcgccgtg gagcaggaca agaacactca ggaagtcttc 2340 gctcaggtga agcaaatcta caagacccca cctatcaagg acttcggcgg attcaacttc 2400 tcccagatcc tgccagaccc ttccaagccc agcaagaggt ctttcatcga ggacctgctg 2460 ttcaacaagg tcactctggc cgacgctggt ttcatcaagc agtacggcga ctgcctggga 2520 gacatcgctg ctcgcgacct gatctgcgcc cagaagttca acggcctgac cgtgctgccc 2580 ccactgctga ctgacgaaat gatcgctcag tacactagcg ccctgctggc tggcaccatc 2640 acttcaggtt ggactttcgg tgctggtgct gctctgcaga tcccattcgc tatgcagatg 2700 gcctaccgtt tcaacggaat cggtgtcacc cagaacgtgc tgtacgagaa ccagaagctg 2760 atcgctaacc agttcaactc agccatcggc aagatccagg acagcctgag ctctactgcc 2820 tctgctctgg gaaagctgca ggacgtcgtg aaccagaacg cccaggctct gaacaccctg 2880 gtcaagcagc tgtcatccaa cttcggcgcc atcagctctg tgctgaacga catcctgtcc 2940 aggctggacc ctcccgaggc tgaagtccag atcgacaggc tgatcactgg aagactgcag 3000 tcactgcaga cctacgtgac tcagcagctg atccgcgccg ctgaaatccg tgcctccgct 3060 aacctggccg ctaccaagat gagcgagtgc gtcctgggcc agtctaagag agtggacttc 3120 tgcggcaagg gataccacct gatgtcattc ccacagtccg cccctcacgg agtcgtgttc 3180 ctgcacgtca cctacgtgcc cgctcaggag aagaacttca ccactgcccc agctatctgc 3240 cacgacggca aggctcactt ccctcgcgaa ggagtcttcg tgagcaacgg cacccactgg 3300 ttcgtcactc agcgtaactt ctacgagccc cagatcatca ccactgacaa cactttcgtg 3360 tctggcaact gcgacgtggt catcggtatc gtcaacaaca ccgtgtacga ccctctgcag 3420 cccgagctgg actcattcaa ggaagagctg gacaagtact tcaagaacca cacctcccct 3480 gacgtcgacc tgggtgacat ctcaggcatc aacgcctccg tcgtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaagt ggctaagaac ctgaacgaaa gcctgatcga cctgcaggag 3600 ctgggcaagt acgaacagta catcaagtgg ccatggtaca tctggctggg attcatcgct 3660 ggcctcatcg ctatcgtgat ggtgaccatc atgctgtgct gcatgacttc atgctgctcc 3720 tgcctgaagg gttgctgcag ctgcggctct tgctgcaagt tcgacgagga cgactctgaa 3780 cctgtcctga agggagtgaa gctgcactac acctaa 3816 <![CDATA[<210> 143]]> <![CDATA[<211> 1269]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 1]]>43 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Phe Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr 245 250 255 Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe 260 265 270 Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys 275 280 285 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr 290 295 300 Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr 305 310 315 320 Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 325 330 335 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 340 345 350 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 355 360 365 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 370 375 380 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 385 390 395 400 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala 405 410 415 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 420 425 430 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 435 440 445 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 450 455 460 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 465 470 475 480 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 485 490 495 Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 500 505 510 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 515 520 525 Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr 530 535 540 Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln 545 550 555 560 Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro 565 570 575 Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val 580 585 590 Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu 595 600 605 Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp 610 615 620 Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe 625 630 635 640 Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser 645 650 655 Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln 660 665 670 Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala Ser Gln Ser 675 680 685 Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala Tyr 690 695 700 Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr 705 710 715 720 Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr 725 730 735 Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln 740 745 750 Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala 755 760 765 Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln 770 775 780 Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn Phe Ser Gln 785 790 795 800 Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp 805 810 815 Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln 820 825 830 Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala 835 840 845 Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu 850 855 860 Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser 865 870 875 880 Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met 885 890 895 Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu 900 905 910 Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly 915 920 925 Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu 930 935 940 Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys 945 950 955 960 Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile 965 970 975 Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu 980 985 990 Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu 995 1000 1005 Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr 1010 1015 1020 Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe 1025 1030 1035 Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro 1040 1045 1050 His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu 1055 1060 1065 Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala 1070 1075 1080 His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp 1085 1090 1095 Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr 1100 1105 1110 Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile 1115 1120 1125 Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser 1130 1135 1140 Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro 1145 1150 1155 Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val 1160 1165 1170 Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn 1175 1180 1185 Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu 1190 1195 1200 Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala 1205 1210 1215 Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met 1220 1225 1230 Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser 1235 1240 1245 Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly 1250 1255 1260 Val Lys Leu His Tyr Thr 1265 <![CDATA[<210> 144]]> <![CDATA[<211> 1256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 144]]> Gln Cys Val Asn Phe 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 20 25 30 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 Ala 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 225 230 235 240 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 245 250 255 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 260 265 270 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 275 280 285 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 290 295 300 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 305 310 315 320 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 325 330 335 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 340 345 350 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 355 360 365 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 370 375 380 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 385 390 395 400 Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 405 410 415 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 420 425 430 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 435 440 445 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 450 455 460 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 465 470 475 480 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 485 490 495 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 500 505 510 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 515 520 525 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 530 535 540 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 545 550 555 560 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 565 570 575 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 580 585 590 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 595 600 605 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 610 615 620 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 625 630 635 640 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 645 650 655 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 660 665 670 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser 675 680 685 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 690 695 700 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 705 710 715 720 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 725 730 735 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 740 745 750 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 755 760 765 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn 770 775 780 Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe 785 790 795 800 Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe 805 810 815 Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu 820 825 830 Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu 835 840 845 Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr 850 855 860 Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro 865 870 875 880 Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln 885 890 895 Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser 900 905 910 Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu 915 920 925 Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr 930 935 940 Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu 945 950 955 960 Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile 965 970 975 Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr 980 985 990 Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 995 1000 1005 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1010 1015 1020 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1025 1030 1035 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1040 1045 1050 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1055 1060 1065 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1070 1075 1080 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1085 1090 1095 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1100 1105 1110 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1115 1120 1125 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1130 1135 1140 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1145 1150 1155 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1160 1165 1170 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1175 1180 1185 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1190 1195 1200 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1205 1210 1215 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1220 1225 1230 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1235 1240 1245 Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 1]]>45 <![CDATA[<211> 3812]]> <![CDATA[<212> DNA]]> <![CDATA[<213> ]]>人工序列 <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 145]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cttcaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcacta ggggtgtgta ctacccagac 120 aaggtcttcc gctcctcagt gctgcactca actcaggacc tgttcctgcc tttcttctcc 180 aacgtcacct ggttccacgc tatccacgtg tccggcacca acggcactaa gaggttcgcc 240 aaccccgtgc tgccattcaa cgacggagtc tacttcgctt caaccgagaa gtccaacatc 300 atcagaggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcta ccaacgtggt catcaaggtg tgcgaattcc agttctgtaa cgaccccttc 420 ctgggtgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc cattcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgcgc gagttcgtgt tcaagaacat cgacggctac 600 ttcaagattt acagcaagca cacccccatc aacctggtcc gtggcctgcc acagggattc 660 tctgctctgg agcccctggt ggacctgcca atcggcatca acatcaccag gttccagact 720 ctgcacagat cctacctgac tcccggagac tcttcatccg gttggaccgc tggcgctgcc 780 gcttactacg tgggttacct gcagccacgc accttcctgc tgaagtacaa cgaaaacggc 840 accatcactg acgccgtcga ctgcgctctg gacccactgt cagaaaccaa gtgcactctg 900 aagtccttca ccgtggagaa gggaatctac cagacttcaa acttccgcgt gcagcctacc 960 gaatccatcg tccgtttccc aaacatcact aacctgtgcc ctttcggaga ggtcttcaac 1020 gccacccgct tcgcttccgt gtacgcctgg aaccgcaagc gtatctcaaa ctgcgtcgct 1080 gactactccg tgctgtacaa ctcagcctcc ttcagcacct tcaagtgcta cggagtgtca 1140 cccactaagc tgaacgacct gtgcttcacc aacgtctacg ctgactcctt cgtgatccgc 1200 ggtgacgagg tccgtcagat cgctccaggc cagactggaa acatcgccga ctacaactac 1260 aagctgcctg acgacttcac cggttgcgtc atcgcctgga acagcaacaa cctggactct 1320 aaagtgggtg gcaactacaa ctacctgtac aggctgttca gaaagtcaaa cctgaagccc 1380 ttcgagcgcg acatcagcac tgaaatctac caggctggtt ctaccccatg caacggtgtc 1440 aagggcttca actgctactt ccctctgcag tcctacggct tccagcccac ttacggtgtg 1500 ggctaccagc cataccgtgt ggtcgtgctg agcttcgagc tgctgcacgc ccctgctact 1560 gtgtgcggac ccaagaagtc taccaacctg gtcaagaaca agtgcgtgaa cttcaacttc 1620 aacggtctga ccggaactgg tgtcctgacc gagagcaaca agaagttcct gcctttccag 1680 cagttcggtc gcgacatcgc tgacaccact gacgccgtgc gtgaccctca gaccctggaa 1740 atcctggaca tcactccctg ctcattcgga ggtgtctccg tgatcactcc cggaaccaac 1800 acttctaacc aggtcgctgt gctgtaccag ggtgtgaact gcaccgaagt cccagtggcc 1860 atccacgctg accagctgac ccctacttgg agggtgtact ccaccggcag caacgtcttc 1920 cagactagag ctggatgcct gatcggtgcc gagcacgtca acaacagcta cgaatgcgac 1980 atccctatcg gcgctggaat ctgcgcctct taccagaccc agactaacag cccccagcag 2040 gctcagtctg tggcctctca gtcaatcatc gcctacacca tgtcactggg tgtcgaaaac 2100 tccgtggctt actctaacaa ctcaatcgcc atccctacca acttcactat cagcgtgacc 2160 actgagatcc tgcccgtcag catgaccaag acttctgtgg actgcactat gtacatctgc 2220 ggcgacagca ccgaatgctc taacctgctg ctgcagtacg gttctttctg cacccagctg 2280 aaccgcgctc tgactggcat cgccgtggag caggacaaga acactcagga agtcttcgct 2340 caggtgaagc aaatctacaa gaccccacct atcaaggact tcggcggatt caacttctcc 2400 cagatcctgc cagacccttc caagcccagc aagaggtctt tcatcgagga cctgctgttc 2460 aacaaggtca ctctggccga cgctggtttc atcaagcagt acggcgactg cctgggagac 2520 atcgctgctc gcgacctgat ctgcgcccag aagttcaacg gcctgaccgt gctgccccca 2580 ctgctgactg acgaaatgat cgctcagtac actagcgccc tgctggctgg caccatcact 2640 tcaggttgga ctttcggtgc tggtgctgct ctgcagatcc cattcgctat gcagatggcc 2700 taccgtttca acggaatcgg tgtcacccag aacgtgctgt acgagaacca gaagctgatc 2760 gctaaccagt tcaactcagc catcggcaag atccaggaca gcctgagctc tactgcctct 2820 gctctgggaa agctgcagga cgtcgtgaac cagaacgccc aggctctgaa caccctggtc 2880 aagcagctgt catccaactt cggcgccatc agctctgtgc tgaacgacat cctgtccagg 2940 ctggaccctc ccgaggctga agtccagatc gacaggctga tcactggaag actgcagtca 3000 ctgcagacct acgtgactca gcagctgatc cgcgccgctg aaatccgtgc ctccgctaac 3060 ctggccgcta ccaagatgag cgagtgcgtc ctgggccagt ctaagagagt ggacttctgc 3120 ggcaagggat accacctgat gtcattccca cagtccgccc ctcacggagt cgtgttcctg 3180 cacgtcacct acgtgcccgc tcaggagaag aacttcacca ctgccccagc tatctgccac 3240 gacggcaagg ctcacttccc tcgcgaagga gtcttcgtga gcaacggcac ccactggttc 3300 gtcactcagc gtaacttcta cgagccccag atcatcacca ctgacaacac tttcgtgtct 3360 ggcaactgcg acgtggtcat cggtatcgtc aacaacaccg tgtacgaccc tctgcagccc 3420 gagctggact cattcaagga agagctggac aagtacttca agaaccacac ctcccctgac 3480 gtcgacctgg gtgacatctc aggcatcaac gcctccgtcg tgaacatcca gaaggagatc 3540 gaccgcctga acgaagtggc taagaacctg aacgaaagcc tgatcgacct gcaggagctg 3600 ggcaagtacg aacagtacat caagtggcca tggtacatct ggctgggatt catcgctggc 3660 ctcatcgcta tcgtgatggt gaccatcatg ctgtgctgca tgacttcatg ctgctcctgc 3720 ctgaagggtt gctgcagctg cggctcttgc tgcaagttcg acgaggacga ctctgaacct 3780 tcctgaaggg agtgaagctg cactacacct aa 3812 <![CDATA[<210> 146]]> <![CDATA[<211>]]> 1267 <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400]]>> 146]]> <br/> <br/><![CDATA[Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Phe Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr 245 250 255 Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe 260 265 270 Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys 275 280 285 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr 290 295 300 Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr 305 310 315 320 Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 325 330 335 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 340 345 350 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 355 360 365 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 370 375 380 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 385 390 395 400 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala 405 410 415 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 420 425 430 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 435 440 445 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 450 455 460 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 465 470 475 480 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 485 490 495 Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 500 505 510 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 515 520 525 Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr 530 535 540 Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln 545 550 555 560 Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro 565 570 575 Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val 580 585 590 Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu 595 600 605 Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp 610 615 620 Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe 625 630 635 640 Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser 645 650 655 Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln 660 665 670 Thr Gln Thr Asn Ser Pro Gly Gly Ser Val Ala Ser Gln Ser Ile Ile 675 680 685 Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala Tyr Ser Asn 690 695 700 Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu 705 710 715 720 Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr 725 730 735 Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly 740 745 750 Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu 755 760 765 Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr 770 775 780 Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn Phe Ser Gln Ile Leu 785 790 795 800 Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu 805 810 815 Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly 820 825 830 Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys 835 840 845 Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile 850 855 860 Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp 865 870 875 880 Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met 885 890 895 Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu 900 905 910 Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile 915 920 925 Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp 930 935 940 Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu 945 950 955 960 Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser 965 970 975 Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr 980 985 990 Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg 995 1000 1005 Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met 1010 1015 1020 Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly 1025 1030 1035 Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly 1040 1045 1050 Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn 1055 1060 1065 Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe 1070 1075 1080 Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val 1085 1090 1095 Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn 1100 1105 1110 Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn 1115 1120 1125 Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys 1130 1135 1140 Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val 1145 1150 1155 Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile 1160 1165 1170 Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn 1175 1180 1185 Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr 1190 1195 1200 Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu 1205 1210 1215 Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser 1220 1225 1230 Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys 1235 1240 1245 Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys 1250 1255 1260 Leu His Tyr Thr 1265 <![CDATA[<210> 147]]> <![CDATA[<211> 1254]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 147]]> Gln Cys Val Asn Phe 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 20 25 30 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 Ala 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 225 230 235 240 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 245 250 255 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 260 265 270 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 275 280 285 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 290 295 300 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 305 310 315 320 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 325 330 335 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 340 345 350 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 355 360 365 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 370 375 380 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 385 390 395 400 Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 405 410 415 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 420 425 430 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 435 440 445 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 450 455 460 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 465 470 475 480 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 485 490 495 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 500 505 510 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 515 520 525 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 530 535 540 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 545 550 555 560 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 565 570 575 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 580 585 590 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 595 600 605 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 610 615 620 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 625 630 635 640 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 645 650 655 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Gly Ser Val Ala Ser Gln 660 665 670 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala 675 680 685 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 690 695 700 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 705 710 715 720 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 725 730 735 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 740 745 750 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 755 760 765 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Asn Phe Ser 770 775 780 Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu 785 790 795 800 Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys 805 810 815 Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys 820 825 830 Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp 835 840 845 Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr 850 855 860 Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala 865 870 875 880 Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val 885 890 895 Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile 900 905 910 Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys 915 920 925 Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val 930 935 940 Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp 945 950 955 960 Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg 965 970 975 Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln 980 985 990 Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr 995 1000 1005 Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe 1010 1015 1020 Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro 1025 1030 1035 His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu 1040 1045 1050 Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala 1055 1060 1065 His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp 1070 1075 1080 Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr 1085 1090 1095 Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile 1100 1105 1110 Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser 1115 1120 1125 Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro 1130 1135 1140 Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val 1145 1150 1155 Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn 1160 1165 1170 Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu 1175 1180 1185 Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala 1190 1195 1200 Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met 1205 1210 1215 Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser 1220 1225 1230 Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly 1235 1240 1245 Val Lys Leu His Tyr Thr 1250 <![CDATA[<210> 148]]> <![CDATA[<211> 3804]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 148]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cttcaccact 60 aggactcagc tgcctcccgc ttacaccaac tcattcacta ggggtgtgta ctacccagac 120 aaggtcttcc gctcctcagt gctgcactca actcaggacc tgttcctgcc tttcttctcc 180 aacgtcacct ggttccacgc tatccacgtg tccggcacca acggcactaa gaggttcgcc 240 aaccccgtgc tgccattcaa cgacggagtc tacttcgctt caaccgagaa gtccaacatc 300 atcagaggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcta ccaacgtggt catcaaggtg tgcgaattcc agttctgtaa cgaccccttc 420 ctgggtgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc cattcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgcgc gagttcgtgt tcaagaacat cgacggctac 600 ttcaagattt acagcaagca cacccccatc aacctggtcc gtggcctgcc acagggattc 660 tctgctctgg agcccctggt ggacctgcca atcggcatca acatcaccag gttccagact 720 ctgcacagat cctacctgac tcccggagac tcttcatccg gttggaccgc tggcgctgcc 780 gcttactacg tgggttacct gcagccacgc accttcctgc tgaagtacaa cgaaaacggc 840 accatcactg acgccgtcga ctgcgctctg gacccactgt cagaaaccaa gtgcactctg 900 aagtccttca ccgtggagaa gggaatctac cagacttcaa acttccgcgt gcagcctacc 960 gaatccatcg tccgtttccc aaacatcact aacctgtgcc ctttcggaga ggtcttcaac 1020 gccacccgct tcgcttccgt gtacgcctgg aaccgcaagc gtatctcaaa ctgcgtcgct 1080 gactactccg tgctgtacaa ctcagcctcc ttcagcacct tcaagtgcta cggagtgtca 1140 cccactaagc tgaacgacct gtgcttcacc aacgtctacg ctgactcctt cgtgatccgc 1200 ggtgacgagg tccgtcagat cgctccaggc cagactggaa acatcgccga ctacaactac 1260 aagctgcctg acgacttcac cggttgcgtc atcgcctgga acagcaacaa cctggactct 1320 aaagtgggtg gcaactacaa ctacctgtac aggctgttca gaaagtcaaa cctgaagccc 1380 ttcgagcgcg acatcagcac tgaaatctac caggctggtt ctaccccatg caacggtgtc 1440 aagggcttca actgctactt ccctctgcag tcctacggct tccagcccac ttacggtgtg 1500 ggctaccagc cataccgtgt ggtcgtgctg agcttcgagc tgctgcacgc ccctgctact 1560 gtgtgcggac ccaagaagtc taccaacctg gtcaagaaca agtgcgtgaa cttcaacttc 1620 aacggtctga ccggaactgg tgtcctgacc gagagcaaca agaagttcct gcctttccag 1680 cagttcggtc gcgacatcgc tgacaccact gacgccgtgc gtgaccctca gaccctggaa 1740 atcctggaca tcactccctg ctcattcgga ggtgtctccg tgatcactcc cggaaccaac 1800 acttctaacc aggtcgctgt gctgtaccag ggtgtgaact gcaccgaagt cccagtggcc 1860 atccacgctg accagctgac ccctacttgg agggtgtact ccaccggcag caacgtcttc 1920 cagactagag ctggatgcct gatcggtgcc gagcacgtca acaacagcta cgaatgcgac 1980 atccctatcg gcgctggaat ctgcgcctct taccagaccc agactaacag cccaggtggt 2040 tctgtggcct ctcagtcaat catcgcctac accatgtcac tgggtgtcga aaactccgtg 2100 gcttactcta acaactcaat cgccatccct accaacttca ctatcagcgt gaccactgag 2160 atcctgcccg tcagcatgac caagacttct gtggactgca ctatgtacat ctgcggcgac 2220 agcaccgaat gctctaacct gctgctgcag tacggttctt tctgcaccca gctgaaccgc 2280 gctctgactg gcatcgccgt ggagcaggac aagaacactc aggaagtctt cgctcaggtg 2340 aagcaaatct acaagacccc acctatcaag gacttcggcg gattcaactt ctcccagatc 2400 ctgccagacc cttccaagcc cagcaagagg tctttcatcg aggacctgct gttcaacaag 2460 gtcactctgg ccgacgctgg tttcatcaag cagtacggcg actgcctggg agacatcgct 2520 gctcgcgacc tgatctgcgc ccagaagttc aacggcctga ccgtgctgcc cccactgctg 2580 actgacgaaa tgatcgctca gtacactagc gccctgctgg ctggcaccat cacttcaggt 2640 tggactttcg gtgctggtgc tgctctgcag atcccattcg ctatgcagat ggcctaccgt 2700 ttcaacggaa tcggtgtcac ccagaacgtg ctgtacgaga accagaagct gatcgctaac 2760 cagttcaact cagccatcgg caagatccag gacagcctga gctctactgc ctctgctctg 2820 ggaaagctgc aggacgtcgt gaaccagaac gcccaggctc tgaacaccct ggtcaagcag 2880 ctgtcatcca acttcggcgc catcagctct gtgctgaacg acatcctgtc caggctggac 2940 cctcccgagg ctgaagtcca gatcgacagg ctgatcactg gaagactgca gtcactgcag 3000 acctacgtga ctcagcagct gatccgcgcc gctgaaatcc gtgcctccgc taacctggcc 3060 gctaccaaga tgagcgagtg cgtcctgggc cagtctaaga gagtggactt ctgcggcaag 3120 ggataccacc tgatgtcatt cccacagtcc gcccctcacg gagtcgtgtt cctgcacgtc 3180 acctacgtgc ccgctcagga gaagaacttc accactgccc cagctatctg ccacgacggc 3240 aaggctcact tccctcgcga aggagtcttc gtgagcaacg gcacccactg gttcgtcact 3300 cagcgtaact tctacgagcc ccagatcatc accactgaca acactttcgt gtctggcaac 3360 tgcgacgtgg tcatcggtat cgtcaacaac accgtgtacg accctctgca gcccgagctg 3420 gactcattca aggaagagct ggacaagtac ttcaagaacc acacctcccc tgacgtcgac 3480 ctgggtgaca tctcaggcat caacgcctcc gtcgtgaaca tccagaagga gatcgaccgc 3540 ctgaacgaag tggctaagaa cctgaacgaa agcctgatcg acctgcagga gctgggcaag 3600 tacgaacagt acatcaagtg gccatggtac atctggctgg gattcatcgc tggcctcatc 3660 gctatcgtga tggtgaccat catgctgtgc tgcatgactt catgctgctc ctgcctgaag 3720 ggttgctgca gctgcggctc ttgctgcaag ttcgacgagg acgactctga acctgtcctg 3780 aagggagtga agctgcacta cacc 3804 <![CDATA[<210> 149]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 149]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Phe Thr Asn Arg Thr Gln Leu Pro Ser Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Tyr Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Ser Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu Tyr Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Ile Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 150]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 150]]> atgttcgtct tcctggtgct gctgcctctg gtgtccagcc agtgcgtgaa cttcaccaac 60 cgcactcagc tgcctagcgc ttacaccaac tctttcacta ggggtgtgta ctaccccgac 120 aaggtcttcc gctcctcagt gctgcactct actcaggacc tgttcctgcc cttcttctct 180 aacgtcacct ggttccacgc catccacgtg agcggcacca acggcactaa gaggttcgac 240 aacccagtgc tgcctttcaa cgacggtgtc tacttcgctt caaccgagaa gtccaacatc 300 atcagaggat ggatcttcgg caccactctg gacagcaaga ctcagtctct gctgatcgtc 360 aacaacgcca ccaacgtggt catcaaggtg tgcgaattcc agttctgcaa ctacccattc 420 ctgggcgtct actaccacaa gaacaacaag tcatggatgg agtccgaatt ccgcgtctac 480 tccagcgcta acaactgcac tttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggaaagcagg gtaacttcaa gaacctgtca gagttcgtgt tcaagaacat cgacggatac 600 ttcaagattt actccaagca caccccaatc aacctggtcc gtgacctgcc tcagggtttc 660 tcagctctgg agccactggt ggacctgcct atcggcatca acatcaccag gttccagact 720 ctgctggctc tgcacagatc ctacctgact ccaggtgact catcttctgg atggactgct 780 ggagctgctg cttactacgt gggttacctg cagcctcgca ccttcctgct gaagtacaac 840 gaaaacggca ccatcactga cgccgtcgac tgcgctctgg accctctgag cgaaaccaag 900 tgcactctga agtctttcac cgtggagaag ggtatctacc agactagcaa cttccgcgtg 960 cagcccaccg aatctatcgt ccgtttccct aacatcacta acctgtgccc cttcggcgag 1020 gtcttcaacg ccacccgttt cgcttccgtg tacgcctgga accgcaagcg tatcagcaac 1080 tgcgtcgctg actactctgt gctgtacaac tcagcctcct tcagcacttt caagtgctac 1140 ggtgtgagcc ctactaagct gaacgacctg tgcttcacca acgtctacgc cgactctttc 1200 gtgatccgcg gcgacgaggt ccgtcagatc gctccaggcc agaccggaac tatcgccgac 1260 tacaactaca agctgcctga cgacttcacc ggctgcgtca tcgcttggaa ctcaaacaac 1320 ctggactcca aagtgggtgg caactacaac tacctgtaca ggctgttcag aaagtcaaac 1380 ctgaagccct tcgagaggga catctcaact gaaatctacc aggccggctc caccccatgc 1440 aacggtgtca agggcttcaa ctgctacttc cccctgcagt cctacggatt ccagccaact 1500 tacggtgtgg gctaccagcc ttacagagtg gtcgtgctgt cattcgaact cctccacgct 1560 cctgctactg tgtgcggacc aaagaagtcc accaacctgg tcaagaacaa gtgcgtgaac 1620 ttcaacttca acggtctgac cggaactggt gtcctgaccg agtcaaacaa gaagttcctg 1680 cccttccagc agttcggtcg cgacatcgct gacactaccg acgccgtgcg tgacccccag 1740 accctggaaa tcctggacat cactccatgc agcttcggag gtgtctctgt gatcactcca 1800 ggaaccaaca cttccaacca ggtcgctgtg ctgtaccagg gtgtcaactg caccgaagtc 1860 cctgtggcca tccacgctga ccagctgacc cccacttgga gggtgtactc caccggcagc 1920 aacgtcttcc agactagagc tggttgcctg atcggcgccg agtacgtgaa caactcatac 1980 gaatgcgaca tccctatcgg cgctggaatc tgcgcctcct accagaccca gactaactca 2040 ccccagcagg ctcagtccgt cgcctctcag tcaatcatcg cttacaccat gagcctgggc 2100 gctgaaaact ctgtggccta ctctaacaac tcaatcgcca tccccaccaa cttcactatc 2160 agcgtgacca ctgagatcct gccagtctca atgaccaaga cttccgtgga ctgcactatg 2220 tacatctgcg gagacagcac cgaatgctct aacctgctgc tgcagtacgg ctctttctgc 2280 acccagctga acagggctct gactggaatc gccgtggagc aggacaagaa cactcaggaa 2340 gtcttcgctc aggtgaagca aatctacaag acccctccca tcaaggactt cggcggattc 2400 aacttctccc agatcctgcc tgacccctcc aagcccagca agcgctcttt catcgaggac 2460 ctgctgttca acaaggtcac cctggccgac gctggcttca tcaagcagta cggagactgc 2520 ctgggtgaca tcgccgctcg tgacctgatc tgcgctcaga agttcaacgg actgaccgtg 2580 ctgccacctc tgctgactga cgaaatgatc gcccagtaca cttcagccct gctggctgga 2640 accatcactt ctggttggac cttcggtgct ggtgctgctc tgcagatccc attcgctatg 2700 cagatggcct accgcttcaa cggaatcggt gtcacccaga acgtgctgta cgagaaccag 2760 aagctgatcg ctaaccagtt caacagcgcc atcggcaaga tccaggactc actgagctct 2820 actgcctccg ctctgggaaa gctgcaggac gtcgtgaacc agaacgccca ggctctgaac 2880 accctggtca agcagctgtc atccaacttc ggagctatca gctctgtgct gaacgacatc 2940 ctctcccgcc tggaccctcc tgaggctgaa gtccagatcg acaggctgat cactggtaga 3000 ctgcagagcc tgcagaccta cgtgactcag cagctgatcc gcgccgctga aatccgtgcc 3060 tctgctaacc tggctgctat caagatgtca gagtgcgtcc tgggacagtc caagagagtg 3120 gacttctgcg gcaagggata ccacctgatg tcattccctc agtccgctcc ccacggtgtc 3180 gtgttcctgc acgtcaccta cgtgccagcc caggagaaga acttcaccac tgcccctgct 3240 atctgccacg acggcaaggc tcacttcccc cgcgaaggtg tcttcgtgag caacggcacc 3300 cactggttcg tcactcagcg taacttctac gagccacaga tcatcaccac tgacaacact 3360 ttcgtgtctg gaaactgcga cgtggtcatc ggtatcgtca acaacaccgt gtacgacccc 3420 ctgcagccag agctggacag cttcaaggaa gagctggaca agtacttcaa gaaccacacc 3480 tctcccgacg tggacctggg cgacatcagc ggaatcaacg cttctttcgt caacatccag 3540 aaggagatcg accgtctgaa cgaagtggcc aagaacctga acgaatcact gatcgacctg 3600 caggagctgg gcaagtacga acagtacatc aagtggccat ggtacatctg gctgggtttc 3660 atcgctggcc tcatcgctat cgtgatggtg accatcatgc tgtgctgcat gacttcatgc 3720 tgctcctgcc tgaagggctg ctgcagctgc ggatcttgct gcaagttcga cgaggacgac 3780 tccgaacctg tcctgaaggg agtgaagctg cactacacct aa 3822 <![CDATA[<210> 151]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 151]]> Gln Cys Val Asn Phe Thr Asn Arg Thr Gln Leu Pro Ser Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 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 Tyr Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Ser 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 Thr 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 435 440 445 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 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu Tyr Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Ile Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 152]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<22]]>0>]]> <br/><![CDATA[<223> 修飾的冠狀病毒S多肽]]> <br/> <br/><![CDATA[<400> 152]]> <br/> <br/><![CDATA[Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ile Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Cys Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Pro Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 153]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 153]]> 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 20 25 30 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Cys Met Glu Ser Glu Phe 130 135 140 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 Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 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 Pro Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 154]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> N末端信號肽]]> <![CDATA[<400> 154]]> Met Phe Val Phe Phe Val Leu Leu Pro Leu Val Ser Ser 1 5 10 <![CDATA[<210> 155]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 155]]> Met Phe Val Phe Phe Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Gly Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 156]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 156]]> 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 20 25 30 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 Ile 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 435 440 445 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 Lys 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 157]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 157]]> Met Phe Val Phe Phe Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Gly Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Asn Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 158]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 修飾的冠狀病毒S多肽]]> <![CDATA[<400> 158]]> 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 20 25 30 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 Ile 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 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Gly 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 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Asn 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Val 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 159]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 159]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 160]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 160]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Lys Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Gln Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala His Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 161]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 161]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Ile 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 162]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 162]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Ser 130 135 140 Asn His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser His Gln Gln Ala Gln Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 163]]> <![CDATA[<211> 1274]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 163]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Thr 130 135 140 Ser Asn His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val 145 150 155 160 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 165 170 175 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 180 185 190 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 195 200 205 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 210 215 220 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 225 230 235 240 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 245 250 255 Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 260 265 270 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 275 280 285 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 290 295 300 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 305 310 315 320 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 325 330 335 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Ala Ser Val Tyr 340 345 350 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 355 360 365 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 370 375 380 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 385 390 395 400 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 405 410 415 Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 420 425 430 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 435 440 445 Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 450 455 460 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro 465 470 475 480 Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 485 490 495 Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 500 505 510 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 515 520 525 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 530 535 540 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 545 550 555 560 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 565 570 575 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 580 585 590 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 595 600 605 Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala 610 615 620 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 625 630 635 640 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 645 650 655 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 660 665 670 Ala Ser Tyr Gln Thr Gln Thr Asn Ser His Gln Gln Ala Gln Ser Val 675 680 685 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 690 695 700 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 705 710 715 720 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 725 730 735 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 740 745 750 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 755 760 765 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 770 775 780 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 785 790 795 800 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 805 810 815 Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 820 825 830 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 835 840 845 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 850 855 860 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 865 870 875 880 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln 885 890 895 Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 900 905 910 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 915 920 925 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser 930 935 940 Ala Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu 945 950 955 960 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 965 970 975 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 980 985 990 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 995 1000 1005 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala 1010 1015 1020 Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser 1025 1030 1035 Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe 1040 1045 1050 Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr 1055 1060 1065 Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys 1070 1075 1080 His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser 1085 1090 1095 Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro 1100 1105 1110 Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp 1115 1120 1125 Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln 1130 1135 1140 Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys 1145 1150 1155 Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile 1160 1165 1170 Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn 1175 1180 1185 Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu 1190 1195 1200 Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp 1205 1210 1215 Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile 1220 1225 1230 Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys 1235 1240 1245 Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu 1250 1255 1260 Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 164]]> <![CDATA[<211> 1258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 164]]> Gln Cys Val Asn Leu Arg 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 20 25 30 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 115 120 125 Asp Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val 130 135 140 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 145 150 155 160 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 165 170 175 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 180 185 190 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 195 200 205 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 210 215 220 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 225 230 235 240 Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 245 250 255 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 260 265 270 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 275 280 285 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 290 295 300 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 305 310 315 320 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 325 330 335 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 340 345 350 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 355 360 365 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 370 375 380 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 385 390 395 400 Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 405 410 415 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 420 425 430 Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 435 440 445 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro 450 455 460 Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 465 470 475 480 Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 485 490 495 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 500 505 510 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 515 520 525 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 530 535 540 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 545 550 555 560 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 565 570 575 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 580 585 590 Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala 595 600 605 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 610 615 620 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 625 630 635 640 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 645 650 655 Ala Ser Tyr Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 785 790 795 800 Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 805 810 815 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 820 825 830 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 835 840 845 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 850 855 860 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln 865 870 875 880 Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 885 890 895 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 900 905 910 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser 915 920 925 Ala Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu 930 935 940 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 945 950 955 960 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 965 970 975 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 980 985 990 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 995 1000 1005 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1010 1015 1020 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1025 1030 1035 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1040 1045 1050 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1055 1060 1065 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1070 1075 1080 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1085 1090 1095 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1100 1105 1110 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1115 1120 1125 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1130 1135 1140 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1145 1150 1155 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1160 1165 1170 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1175 1180 1185 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1190 1195 1200 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1205 1210 1215 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1220 1225 1230 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1235 1240 1245 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 165]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 165]]> 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 20 25 30 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 Ile 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 115 120 125 Asp Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Lys Ser Glu Phe 130 135 140 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 Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 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 Gln 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 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala His Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 166]]> <![CDATA[<211> 1258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 166]]> Gln Cys Val Asn Leu Arg 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 20 25 30 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 115 120 125 Asp Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val 130 135 140 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 145 150 155 160 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 165 170 175 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 180 185 190 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 195 200 205 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 210 215 220 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 225 230 235 240 Ser Gly Ile Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 245 250 255 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 260 265 270 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 275 280 285 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 290 295 300 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 305 310 315 320 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 325 330 335 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 340 345 350 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 355 360 365 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 370 375 380 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 385 390 395 400 Gly Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 405 410 415 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 420 425 430 Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 435 440 445 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro 450 455 460 Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 465 470 475 480 Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 485 490 495 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 500 505 510 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 515 520 525 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 530 535 540 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 545 550 555 560 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 565 570 575 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 580 585 590 Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala 595 600 605 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 610 615 620 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 625 630 635 640 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 645 650 655 Ala Ser Tyr Gln Thr Gln Thr Asn Ser Arg Gln Gln Ala Gln Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 785 790 795 800 Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 805 810 815 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 820 825 830 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 835 840 845 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 850 855 860 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln 865 870 875 880 Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 885 890 895 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 900 905 910 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser 915 920 925 Ala Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu 930 935 940 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 945 950 955 960 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 965 970 975 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 980 985 990 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 995 1000 1005 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1010 1015 1020 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1025 1030 1035 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1040 1045 1050 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1055 1060 1065 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1070 1075 1080 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1085 1090 1095 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1100 1105 1110 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1115 1120 1125 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1130 1135 1140 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1145 1150 1155 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1160 1165 1170 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1175 1180 1185 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1190 1195 1200 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1205 1210 1215 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1220 1225 1230 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1235 1240 1245 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 167]]> <![CDATA[<211> 1260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 167]]> 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 20 25 30 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 Ile 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 115 120 125 Gly Val Ser Asn His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 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 Lys 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 435 440 445 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 Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 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 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser His Gln Gln Ala Gln 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 1190 1195 1200 Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr 1205 1210 1215 Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly 1220 1225 1230 Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 1235 1240 1245 Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 168]]> <![CDATA[<211> 1261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 重組SARS-CoV-2 S多肽]]> <![CDATA[<400> 168]]> 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 20 25 30 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 Ile 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 115 120 125 Gly Val Thr Ser Asn His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu 130 135 140 Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser 145 150 155 160 Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn 165 170 175 Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr 180 185 190 Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe 195 200 205 Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr 210 215 220 Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly 225 230 235 240 Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly 245 250 255 Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr 260 265 270 Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys 275 280 285 Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser 290 295 300 Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile 305 310 315 320 Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Ala 325 330 335 Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp 340 345 350 Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr 355 360 365 Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr 370 375 380 Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro 385 390 395 400 Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 405 410 415 Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys 420 425 430 Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn 435 440 445 Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly 450 455 460 Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu 465 470 475 480 Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr 485 490 495 Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val 500 505 510 Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn 515 520 525 Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn 530 535 540 Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr 545 550 555 560 Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr 565 570 575 Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr 580 585 590 Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val 595 600 605 Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr 610 615 620 Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly 625 630 635 640 Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala 645 650 655 Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser His Gln Gln Ala 660 665 670 Gln Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly 675 680 685 Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr 690 695 700 Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr 705 710 715 720 Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu 725 730 735 Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn 740 745 750 Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu 755 760 765 Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp 770 775 780 Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro 785 790 795 800 Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu 805 810 815 Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile 820 825 830 Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val 835 840 845 Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala 850 855 860 Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala 865 870 875 880 Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly 885 890 895 Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala 900 905 910 Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser 915 920 925 Thr Ala Ser Ala Leu Gly Lys Leu Gln Asn Val Val Asn Gln Asn Ala 930 935 940 Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala 945 950 955 960 Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu 965 970 975 Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 980 985 990 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala 995 1000 1005 Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly 1010 1015 1020 Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met 1025 1030 1035 Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val 1040 1045 1050 Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala 1055 1060 1065 Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe 1070 1075 1080 Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr 1085 1090 1095 Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn 1100 1105 1110 Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro 1115 1120 1125 Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr 1130 1135 1140 Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser 1145 1150 1155 Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg 1160 1165 1170 Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu 1175 1180 1185 Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr 1190 1195 1200 Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val 1205 1210 1215 Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys 1220 1225 1230 Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp 1235 1240 1245 Ser Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 1250 1255 1260 <![CDATA[<210> 169]]> <![CDATA[<211> 20]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 2019-nCoV_N1-F]]> <![CDATA[<400> 169]]> gaccccaaaa tcagcgaaat 20 <![CDATA[<210> 170]]> <![CDATA[<211> 24]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 2019-nCoV_N1-R]]> <![CDATA[<400> 170]]> tctggttact gccagttgaa tctg 24 <![CDATA[<210> 171]]> <![CDATA[<211> 24]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 2019-nCoV_N1-P]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (1)..(1)]]> <![CDATA[<223> 附接的6-羧基螢光素部分]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (9)..(10)]]> <![CDATA[<223> 由內部ZEN淬滅劑部分連接]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (24)..(24)]]> <![CDATA[<223> 附接的Iowa Black FQ淬滅劑部分]]> <![CDATA[<400> 171]]> accccgcatt acgtttggtg gacc 24 <![CDATA[<210> 172]]> <![CDATA[<211> 23]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Sg-N-F]]> <![CDATA[<400> 172]]> cgatctcttg tagatctgtt ctc 23 <![CDATA[<210> 173]]> <![CDATA[<211> 20]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Sg-N-R]]> <![CDATA[<400> 173]]> ggtgaaccaa gacgcagtat 20 <![CDATA[<210> 174]]> <![CDATA[<211> 25]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Sg-N-P]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (1)..(1)]]> <![CDATA[<223> 附接的6-羧基螢光素部分]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (9)..(10)]]> <![CDATA[<223> 由內部ZEN淬滅劑部分連接]]> <![CDATA[<220>]]> <![CDATA[<221> 尚未歸類的特徵]]> <![CDATA[<222> (25)..(25)]]> <![CDATA[<223> 附接的Iowa Black FQ淬滅劑部分]]> <![CDATA[<400> 174]]> taaccagaat ggagaacgca gtggg 25
無。
Claims (36)
- 一種免疫原性組合物,其包含: (a) 處於去污劑-核心奈米顆粒形式的冠狀病毒S(CoV S)醣蛋白,其中所述去污劑是非離子去污劑; (b) 至少三種血凝素(HA)醣蛋白,其中每種HA醣蛋白來自不同的流感毒株;以及 (c) 醫藥上可接受的緩衝液。
- 如請求項1所述的免疫原性組合物,其中所述至少三種HA醣蛋白處於選自以下的形式: (a) 包含血凝素(HA)的去污劑-核心奈米顆粒; (b) HaSMaN(血凝素皂苷基質奈米顆粒); (c) 滅活的全流感病毒; (d) 從流感病毒提取的血凝素組合物;任選地流感裂解病毒粒子組合物或亞單位流感病毒組合物; 以及它們的任何組合。
- 如請求項2所述的免疫原性組合物,其中至少一種HA醣蛋白處於包含HA的去污劑-核心奈米顆粒的形式,並且至少一種HA醣蛋白處於HaSMaN的形式。
- 如請求項3所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒的血凝素醣蛋白來自乙型流感毒株。
- 如請求項3所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒的血凝素醣蛋白來自甲型流感毒株。
- 如請求項3所述的免疫原性組合物,其中所述去污劑-核心奈米顆粒是胰蛋白酶抗性奈米顆粒。
- 如請求項3所述的免疫原性組合物,其中所述HaSMaN是胰蛋白酶抗性奈米顆粒。
- 如請求項1-7中任一項所述的免疫原性組合物,其中每種HA醣蛋白來自不同的流感毒株。
- 如請求項1-8中任一項所述的免疫原性組合物,其包含多至4種、多至5種、多至6種、多至7種、多至8種、多至9種或多至10種HA醣蛋白。
- 如請求項1-9中任一項所述的免疫原性組合物,其中每種HA醣蛋白都處於奈米顆粒的形式。
- 如請求項10所述的免疫原性組合物,其中每個奈米顆粒包含來自單一流感毒株的HA醣蛋白。
- 如請求項11所述的免疫原性組合物,其中每個奈米顆粒是去污劑-核心奈米顆粒或HaSMaN。
- 如請求項1-12中任一項所述的免疫原性組合物,其包含佐劑。
- 如請求項13所述的免疫原性組合物,其中所述佐劑是皂苷佐劑。
- 如請求項14所述的免疫原性組合物,其中所述皂苷佐劑包含至少兩種iscom顆粒,其中: 第一iscom顆粒包含皂樹的級分A,且不包含皂樹的級分C;並且 第二iscom顆粒包含皂樹的級分C,且不包含皂樹的級分A。
- 如請求項15所述的免疫原性組合物,其中分別地,皂樹的級分A占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計50%-96%,並且皂樹的級分C占剩餘部分。
- 如請求項15所述的免疫原性組合物,其中皂樹的級分A和皂樹的級分C分別占在所述佐劑中皂樹的級分A和皂樹的級分C的重量之和的按重量計約85%和按重量計約15%。
- 如請求項13-17中任一項所述的免疫原性組合物,其包含約50 µg或約75 µg的皂苷佐劑。
- 如請求項1-18中任一項所述的免疫原性組合物,其中所述去污劑是PS80。
- 如請求項1-19中任一項所述的免疫原性組合物,其中所述流感毒株是選自H1、H2、H3、H4、H5、H6、H7、H8、H9、H10、H11、H12、H13、H14、H15、H16、H17和H18的亞型的毒株。
- 如請求項1-20中任一項所述的免疫原性組合物,其中所述醫藥上可接受的緩衝液包含 (i) 約25 mM的磷酸鈉;(ii) 約150 mM的氯化鈉;(iii) 約100 mM的鹽酸精胺酸;(iv) 約5%的海藻糖;其中所述組合物的pH為約7.5。
- 如請求項1-21中任一項所述的免疫原性組合物,其中所述CoV S醣蛋白包含: (i) 具有滅活的弗林蛋白酶切割位點的S1亞基,其中所述S1亞基包含N末端結構域(NTD)、受體結合結構域(RBD)、亞結構域1和亞結構域2(SD1/2),其中所述滅活的弗林蛋白酶切割位點具有QQAQ的胺基酸序列(SEQ ID NO: 7); 其中所述NTD任選地包含選自以下的一個或多個修飾: (a) 選自胺基酸56、57、131、132、144、145、228、229、230、231、234、235、236、237、238、239、240及其組合的一個或多個胺基酸的缺失; (b) 在胺基酸132後1、2、3或4個胺基酸的插入;以及 (c) 選自胺基酸5、6、7、13、51、53、56、57、62、63、67、82、125、129、131、132、133、139、143、144、145、177、200、201、202、209、229、233、240、245及其組合的一個或多個胺基酸的突變; 其中所述RBD任選地包含選自胺基酸333、404、419、426、439、440、464、465、471、477、481、488及其組合的一個或多個胺基酸的突變; 其中所述SD1/2結構域任選地包含選自557、600、601、642、664、668及其組合的一個或多個胺基酸的突變;以及 (ii) S2亞基,其中胺基酸973和974是脯胺酸, 其中所述S2亞基任選地包含選自以下的一個或多個修飾: (a) 一個或多個胺基酸從676-685、676-702、702-711、775-793、806-815及其組合的缺失; (b) 選自688、703、846、875、937、969、1014、1058、1105和1163及其組合的一個或多個胺基酸的突變;以及 (c) 自TMCT的一個或多個胺基酸的缺失; 其中所述CoV S醣蛋白的胺基酸相對於具有SEQ ID NO: 2的序列的多肽編號。
- 如請求項22所述的免疫原性組合物,其中所述CoV S醣蛋白包含與SEQ ID NO: 86-89、105、106、112-115和164-168中的任一個具有至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性的胺基酸序列或由所述胺基酸序列組成。
- 如請求項23所述的免疫原性組合物,其中所述CoV S醣蛋白包含與SEQ ID NO: 87至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%相同的序列。
- 如請求項1-24中任一項所述的免疫原性組合物,其包含約1 µg至約50 µg的CoV S醣蛋白和約5 µg至約60 µg的血凝素/毒株。
- 如請求項25所述的免疫原性組合物,其包含約20 µg至約50 µg的CoV S醣蛋白和約24 µg至約40 µg的血凝素/毒株。
- 如請求項1-26中任一項所述的免疫原性組合物,其包含約3 µg、約5 µg、約25 µg、約22.5 µg、約7.5 µg或約2.5 µg的冠狀病毒S醣蛋白。
- 如請求項1-26中任一項所述的免疫原性組合物,其包含約5 µg、約10 µg、約24 µg、約25 µg、約26 µg、約27 µg、約28 µg、約29 µg、約30 µg、約31 µg、約32 µg、約33 µg、約34 µg、約35 µg、約36 µg、約37 µg、約38 µg、約39 µg、約40 µg或約60 µg的血凝素/毒株。
- 一種在受試者中刺激針對SARS-CoV-2、異源SARS-CoV-2毒株、流感病毒或其組合的免疫反應的方法,其包括投予如請求項1-28中任一項所述的免疫原性組合物。
- 如請求項29所述的方法,其中向所述受試者在第0天投予第一劑量,並且在第56天投予加強劑量。
- 如請求項29或30所述的方法,其中將所述免疫原性組合物肌內投予。
- 如請求項29-31中任一項所述的方法,其中投予單劑量的所述免疫原性組合物。
- 如請求項30所述的方法,其中所述異源SARS-CoV-2毒株選自Cal.20C SARS-CoV-2毒株、P.1 SARS-CoV-2毒株、B.1.351 SARS-CoV-2毒株、B.1.1.7 SARS-CoV-2毒株、SARS-CoV-2 B.1.617.2毒株、B.1.525毒株、B.1.526毒株、B.1.617.1毒株、C.37毒株、B.1.621毒株或SARS-CoV-2 ο毒株。
- 如請求項29-33中任一項所述的方法,其中所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是至少50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約91%、至少約92%、至少約93%、至少約94%、至少約95%、至少約96%、至少約97%、至少約98%或至少約99%或約100%。
- 如請求項29-33中任一項所述的方法,其中所述免疫原性組合物用於預防冠狀病毒疾病-19(COVID-19)的功效在投予所述免疫原性組合物後多至約2個月、多至約2.5個月、多至約3個月、多至約3.5個月、多至約4個月、多至約4.5個月、多至約5個月、多至約5.5個月、多至約6個月、多至約6.5個月、多至約7個月、多至約7.5個月、多至約8個月、多至約8.5個月、多至約9個月、多至約9.5個月、多至約10個月、多至約10.5個月、多至約11個月、多至約11.5個月或多至約12個月內是約50%至約99%、約50%至約95%、約50%至約90%、約50%至約85%、約50%至約80%、約60%至約99%、約60%至約95%、約60%至約90%、約60%至約85%、約60%至約80%、約40%至約99%、約40%至約95%、約40%至約90%、約40%至約85%、約40%至約80%、約40%至約75%、約40%至約70%、約40%至約65%、約40%至約55%或約40%至約50%。
- 一種載藥注射器,其包含如請求項1-28中任一項所述的免疫原性組合物。
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