Safety and Immunogenicity of the Candidate Tuberculosis Vaccine MVA85A in West Africa 英文参考文献.docVIP

SafetyandImmunogenicityoftheCandidate TuberculosisVaccineMVA85AinWestAfrica RogerH.Brookes1,PhilipC.Hill1,PatrickK.Owiafe1,HannahB.Ibanga1,DavidJ.Jeffries1,SimonA. Donkor1,HelenA.Fletcher2,AbdulrahmanS.Hammond1,ChristianLienhardt3,RichardA.Adegbola1, HelenMcShane2*,AdrianV.S.Hill2,4 1BacterialDiseasesProgramme,TuberculosisDivision,MedicalResearchCouncilLaboratories,Fajara,Banjul,TheGambia,2CentreforClinicalVaccinologyandTropical Medicine,UniversityofOxford,ChurchillHospital,Oxford,UnitedKingdom,3InstitutdeRecherchepourleDe′veloppement, Paris,France,4WellcomeTrustCentrefor HumanGenetics,UniversityofOxford,Oxford,UnitedKingdom Abstract Background: Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicityofthisnewvaccineinWestAfricanvolunteers. MethodsandFindings:Wevaccinated21healthyadultmalesubjects(11BCGscarnegativeand10BCGscarpositive)with MVA85Aafterscreeningforevidenceofpriorexposuretomycobacteria.Wemonitoredthemoversixmonths,observingfor clinical,haematologicalandbiochemicaladverseevents,togetherwithassessmentofthevaccineinducedcellularimmune responseusingELISPOTandflowcytometry.MVA85Awaswelltoleratedwithnosignificantadverseevents.Mildlocaland systemicadverseeventswereconsistentwithpreviousUKtrials.Markedimmunogenicitywasfoundwhetherindividuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-na?¨ve Gambians than previously studied BCG-na?¨ve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis. Conclusions:ThesedataonthesafetyandimmunogenicityofMVA85AinWestAfricasupportitsa