Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
Ryan S RoarkHui LiWilton B WilliamsHema ChugRosemarie D MasonJason GormanShuyi WangFang-Hua LeeJuliette RandoMattia BonsignoriKwan-Ki HwangKevin O SaundersKevin WieheM Anthony MoodyPeter T HraberKshitij WaghElena E GiorgiRonnie M RussellFrederic Bibollet-RucheWeimin LiuAndrew Jesse ConnellAndrew G SmithJulia DeVotoAlexander I MurphyJessica SmithWenge DingChengyan ZhaoNeha ChohanMaho OkumuraChristina RosarioYu DingEmily LindemuthAnya M BauerKatharine J BarDavid AmbrozakCara W ChaoGwo-Yu ChuangHui GengBob C LinMark K LouderRichard NguyenBaoshan ZhangMark G LewisDonald D RaymondNicole A Doria-RoseChaim A SchrammDaniel C DouekMario RoedererThomas B KeplerGarnett KelsoeJohn R MascolaPeter D KwongBette T KorberStephen C HarrisonBarton F HaynesBeatrice H HahnGeorge M ShawPublished in: Science (New York, N.Y.) (2020)
Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.