Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies 英文参考文献.docVIP

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Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies 英文参考文献.doc

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Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies 英文参考文献

ProtectioninMacaquesImmunizedwithHIV-1Candidate VaccinesCanBePredictedUsingtheKineticsofTheir NeutralizingAntibodies DavidDavis1*,WimKoornstra1,DaniellaMortier1,ZahraFagrouch1,ErnstJ.Verschoor1,JonathanL. Heeney1,2,WillyM.J.M.Bogers1 1DepartmentofVirology,BiomedicalPrimateResearchCentre,Rijswijk,TheNetherlands,2LaboratoryofViralZoonotics,UniversityofCambridge,Cambridge,United Kingdom Abstract Background:Avaccineisneededtocontrolthespreadofhumanimmunodeficiencyvirustype1(HIV-1).Aninvitroassay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidatewouldbeanassaytoquantifyneutralizationofHIV-1. MethodsandFindings:WehaveusedserafromrhesusmacaquesthathavebeenimmunizedwithHIVcandidatevaccines andsubsequentlychallengedwithsimianhumanimmunodeficiencyvirus(SHIV).Wecomparedneutralizationassayswith different formats. In experiments with the standardized and validated TZMbl assay, neutralizing antibody titers against homologousSHIVSF162P4 pseudovirusgaveavariablecorrelationwithreductionsinplasmaviremialevels.Thetargetcells usedintheassaysarenotjustpassiveindicatorsofvirusinfectionbutareactivelyinvolvedintheneutralizationprocess. When replicating virus was used with GHOST cell assays, events during the absorption phase, as well as the incubation phase,determinethelevelofneutralization.Serathatareassociatedwithprotectionhavepropertiesthatareclosesttothe traditionalconceptofneutralization:theconcentrationofantibodypresentduringtheabsorptionphasehasnoeffecton theinactivationrate.InGHOSTassays,eventsduringtheabsorptionphasemayinactivateafixednumber,ratherthana proportion,ofvirussothatwhilecompleteneutralizationcanbeobtained,itcanonlybefoundatlowdosesparticularly withisolatesthatarerelativelyresistanttoneutralization. Conclusions:Twoscenarioshavethepotentialtopredictprotectionbyneutralizingantibodiesatconcentrationsthatcan beinducedbyvaccination:antibodiesthathavepropertiesclosetothetraditionalconceptofneutraliz