Oral Immunization with a Live CoxsackievirusHIV Recombinant Induces Gag p24-Specific T Cell Responses 英文参考文献.docVIP

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Oral Immunization with a Live CoxsackievirusHIV Recombinant Induces Gag p24-Specific T Cell Responses 英文参考文献.doc

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Oral Immunization with a Live CoxsackievirusHIV Recombinant Induces Gag p24-Specific T Cell Responses 英文参考文献

OralImmunizationwithaLiveCoxsackievirus/HIV RecombinantInducesGagp24-SpecificTCellResponses RuiGu1.,AnaeShampang1.,TouficNashar1,ManishaPatil1,DeborahH.Fuller2,ArleneI.Ramsingh1* 1DivisionofInfectiousDiseases,WadsworthCenter,NewYorkStateDepartmentofHealth,Albany,NewYork,UnitedStatesofAmerica,2CenterforImmunologyand MicrobialDisease,AlbanyMedicalCollege,Albany,NewYork,UnitedStatesofAmerica Abstract Background:ThedevelopmentofanHIV/AIDSvaccinehasproventobeelusive.Becausehumanvaccinetrialshavenotyet demonstratedefficacy,newvaccinestrategiesareneededfortheHIVvaccinepipeline.WehavebeendevelopinganewHIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for developmentas avaccinevector fororaldelivery,becausethese virusesnormallyenterthebody viatheoralrouteand survivetheacidicenvironmentofthestomach. Methodology/Principal Findings: We constructed a live coxsackievirus B4 recombinant, CVB4/p24(733), that expresses seventy-threeaminoacidsofthegagp24sequence(HXB2)andassessedTcellresponsesafterimmunizationofmice.The CVB4recombinantwasphysicallystable,replication-competent,andgeneticallystable.Oralorintraperitonealimmunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-c ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(733) resulted in a short-lived, localized infectionofthegutwithoutsystemicspread.Becausecoxsackievirusesareubiquitousinthehumanpopulation,wealso evaluatedwhethertherecombinantwasabletoinducegagp24-specificTcellresponsesinmicepre-immunizedwiththe CVB4vector.WeshowedthatoralimmunizationwithCVB4/p24(733)inducedgagp24-specificimmuneresponsesinvector- immunemice. Conclusions/Significance: The CVB4/p24(733) recombinant retained the physical and biological characteristics of the parentalCVB4vector.OralimmunizationwiththeCVB4recombinantwassafeandresultedintheinductionofsystemicHIV- specificTcellresponses.