Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
S Munir AlamBaptiste AussedatYusuf VohraR Ryan MeyerhoffEvan M CaleWilliam E WalkowiczNathan A RadakovichKara AnastiLawrence ArmandRobert ParksLaura L SutherlandRichard ScearceM Gordon JoyceMarie PanceraAliaksandr DruzIvelin S GeorgievTarra A Von HolleAmanda EatonChristopher FoxSteven G ReedMark K LouderRobert T BailerLynn MorrisSalim S Abdool KarimMyron S CohenHua-Xin LiaoDavid C MontefioriPeter K ParkAlberto Fernández-TejadaKevin WieheSampa SantraThomas B KeplerKevin O SaundersJoseph G SodroskiPeter D KwongJohn R MascolaMattia BonsignoriM Anthony MoodySamuel DanishefskyBarton F HaynesPublished in: Science translational medicine (2017)
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.