Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes 英文参考文献.docVIP

Anti-V3MonoclonalAntibodiesDisplayBroad NeutralizingActivitiesagainstMultipleHIV-1Subtypes CatarinaE.Hioe1,2*,TerriWrin3,MichaelS.Seaman4,XuesongYu5,BlakeWood5,SteveSelf5 ,Constance Williams1,MiroslawK.Gorny1,SusanZolla-Pazner1,2 1Department of Pathology, New York University Langone School of Medicine, New York, New York, United States of America, 2Veterans Affairs New York Harbor HealthcareSystem,NewYork,NewYork,UnitedStatesofAmerica,3MonogramBiosciences,Inc.,SouthSanFrancisco,California,UnitedStatesofAmerica,4Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 5Public HealthSciencesDivision,StatisticalCenterforHIV/AIDSResearchandPrevention,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica Abstract Background: The V3 loop of the HIV-1 envelope (Env) glycoprotein gp120 was identified as the ‘‘principal neutralizing domain’’ of HIV-1, but has been considered too variable to serve as a neutralizing antibody (Ab) target. Structural and immunochemicaldatasuggest,however,thatV3containsconservedelementswhichexplainitsroleinbindingtovirusco- receptorsdespiteitssequencevariability.DespitethisevidenceofV3conservation,theabilityofanti-V3Abstoneutralizea significantproportionofHIV-1isolatesfromdifferentsubtypes(clades)hasremainedcontroversial. Methods: HIV-1 neutralization experiments were conducted in two independent laboratories to test human anti-V3 monoclonalAbs(mAbs)againstpseudoviruses(psVs)expressingEnvsofdiverseHIV-1subtypesfromsubjectswithacute and chronic infections. Neutralization was defined by 50% inhibitory concentrations (IC50), and was statistically assessed basedontheareaundertheneutralizationtitrationcurves(AUC). Results:UsingAUCanalyses,statisticallysignificantneutralizationwasobservedby$1anti-V3mAbsagainst56/98(57%) psVsexpressingEnvsofdiversesubtypes,includingsubtypesA,AG,B,CandD.Evenwhenthe10Tier1psVstestedwere exc