Author:
Roark Ryan S.,Li Hui,Williams Wilton B.,Chug Hema,Mason Rosemarie D.,Gorman Jason,Wang Shuyi,Lee Fang-Hua,Rando Juliette,Bonsignori Mattia,Hwang Kwan-Ki,Saunders Kevin O.,Wiehe Kevin,Moody M. Anthony,Hraber Peter T.,Wagh Kshitij,Giorgi Elena E.,Russell Ronnie M.,Bibollet-Ruche Frederic,Liu Weimin,Connell Jesse,Smith Andrew G.,DeVoto Julia,Murphy Alexander I.,Smith Jessica,Ding Wenge,Zhao Chengyan,Chohan Neha,Okumura Maho,Rosario Christina,Ding Yu,Lindemuth Emily,Bauer Anya M.,Bar Katharine J.,Ambrozak David,Chao Cara W.,Chuang Gwo-Yu,Geng Hui,Lin Bob C.,Louder Mark K.,Nguyen Richard,Zhang Baoshan,Lewis Mark G.,Raymond Donald,Doria-Rose Nicole A.,Schramm Chaim A.,Douek Daniel C.,Roederer Mario,Kepler Thomas B.,Kelsoe Garnett,Mascola John R.,Kwong Peter D.,Korber Bette T.,Harrison Stephen C.,Haynes Barton F.,Hahn Beatrice H.,Shaw George M.
Abstract
ABSTRACTNeutralizing antibodies elicited by HIV-1 coevolve with viral Envs in distinctive patterns, in some cases acquiring substantial breadth. Here we show that primary HIV-1 Envs, when expressed by simian-human immunodeficiency viruses in rhesus macaques, elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included 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 bNAbs PGT145/PCT64-35M. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.One sentence summaryVirus-antibody coevolution in rhesus macaques recapitulates developmental features of human antibodies.
Publisher
Cold Spring Harbor Laboratory