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1、VIRALIMMUNOLOGYOriginalArticlesVolume26,Number2,2013ªMaryAnnLiebert,Inc.Pp.126–132DOI:10.1089/vim.2012.0076ImmunogenicityandProtectionEfficacyofMonomericandTrimericRecombinantSARSCoronavirusSpikeProteinSubunitVaccineCandidates1,22221JieLi,LauraUlitzky,EricaSilbe
2、rstein,DeborahR.Taylor,andRaphaelViscidiAbstractSevereacuterespiratorysyndrome(SARS)isanewlyemerginginfectiousdisease,andaneffectivevaccineisnotavailable.Inthisstudy,wecomparedtheimmunogenicityandprotectionefficacyofrecombinantproteinscorrespondingtodifferentdom
3、ainsoftheSARS-coronavirusspikeprotein.TrimericrecombinantproteinswerecreatedbyfusingthefoldondomainderivedfromT4bacteriophagetothecarboxy-terminiofindividualdo-mainsofthespikeprotein.Whilethefull-lengthectodomain(S)ofthespikeprotein,thefull-lengthectodomainfuse
4、dtofoldon(S-foldon),theS1domain(S1),S1-foldon,andtheS2domain(S2)antigensallelicitedcomparableantibodytitersasmeasuredbyELISA,S-foldoninducedasignificantlyhighertiterofneutralizingantibodyandS2proteindidnotelicitvirusneutralizingantibodies.Whentestedinamousevirus
5、replicationmodel,allthemicevaccinatedwiththeS1,S1-foldon,S,orS-foldonwerecompletelyprotected.IntroductionsideredamaintargetforSARSvaccines(6).Inthepresentstudy,wecomparedthefull-lengthectodomainofSproteinSevereacuterespiratorysyndrome(SARS)-associatedanditsfrag
6、ments(S1andS2domains)withrespecttoim-coronavirus(SARS-CoV)isanemerginginfectiouspath-munogenicityandprotectionagainstviralinfectioninmice.ogenofzoonoticorigin.AlthoughnonewcasesofSARShaveInitsnativestate,Sproteinisatrimer;however,whenitsbeenreportedsince2004,SA
7、RShasthepotentialtore-emergeectodomainisexpressedasarecombinantproteinineu-fromananimalreservoirorthroughaccidentalorintentionalkaryoticsystems,theproteinexistspredominantlyinamo-release.Therefore,thedevelopmentofeffectivevaccinesisnomericform(7).Tomaketrimeric
8、recombinantspikehighlydesirableforthepreventionandcontainmentoffutureproteins,weexploiteda27-aminoacidsequence,calledtheoutbreaksofSARS.foldondomain,whichwasidentifiedintheba