Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth
Ryan S Roark,
Wilton B Williams,
Rosemarie D. Mason,
Kevin O. Saunders,
M Anthony Moody,
Peter T Hraber,
Elena E. Giorgi,
Ronnie M Russell,
Andrew G Smith,
Alexander I Murphy,
Anya M Bauer,
Katharine J Bar,
Cara W. Chao,
Bob C Lin,
Mark K. Louder,
Mark G Lewis,
Nicole A. Doria-Rose,
Chaim A Schramm,
Daniel C Douek,
Thomas B. Kepler,
John R. Mascola,
Peter D. Kwong,
Stephen C Harrison,
Barton F Haynes,
Beatrice H. Hahn,
George M Shaw
Posted 05 Aug 2020
bioRxiv DOI: 10.1101/2020.08.05.237693 (published DOI: 10.1126/science.abd2638)
Posted 05 Aug 2020
Neutralizing 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. ### Competing Interest Statement The authors have declared no competing interest.
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