Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques 英文参考文献.docVIP

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Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques 英文参考文献.doc

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Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques 英文参考文献

EarlyPotentProtectionagainstHeterologousSIVsmE660 ChallengeFollowingLiveAttenuatedSIVVaccinationin MauritianCynomolgusMacaques NeilBerry1*,ClaireHam1,EdwardT.Mee1,NicolaJ.Rose1,GiadaMattiuzzo1,AdrianJenkins1 ,Mark Page1,WilliamElsley1,MarkRobinson1,DeborahSmith1,DeborahFerguson1,GregTowers3 ,Neil Almond1,RichardStebbings2 1Division of Retrovirology, National Institute for Biological Standards and Control (NIBSC), Health Protection Agency (HPA), South Mimms, Potters Bar, Hertfordshire, United Kingdom, 2Division of Biotherapeutics, NIBSC/HPA, South Mimms, Potters Bar, Hertfordshire, United Kingdom, 3MRC Centre for Medical Molecular Virology, DivisionofInfectionandImmunity,UniversityCollegeLondon,London,UnitedKingdom Abstract Background: Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinatingmacaquesagainstpathogenicSIVchallenge.However,thusfar,protectionhasbeendemonstratedtobemore effectiveagainsthomologousthanheterologousstrains.Immunecorrelatesofvaccine-inducedprotectionhavealsobeen difficulttoidentify,particularlythosemeasurableintheperipheralcirculation. Methodology/Principal Findings: Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccinationwithliveattenuatedSIVmac251/C8.MCMprovidedacharacterisedhostgeneticbackgroundwithlimitedMajor Histocompatibility Complex (MHC) and TRIM5a allelic diversity. Early protection, observed as soon as 3 weeks post- vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthroughcaseswheresimultaneousidentificationofvaccineandchallengevirusesbyvirus-specificPCRwasindicative ofactiveco-infection.PersistenceofthevaccinevirusinarangeoflymphoidtissueswastypifiedbyaconsistentlevelofSIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II hap