Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Roark, RS; Li, H; Williams, WB; Chug, H; Mason, RD; Gorman, J; Wang, S; Lee, F-H; Rando, J; Bonsignori, M; Hwang, K-K; Saunders, KO; Wiehe, K; Moody, MA; Hraber, PT; Wagh, K; Giorgi, EE; Russell, RM; Bibollet-Ruche, F; Liu, W; Connell, J; Smith, AG; DeVoto, J; Murphy, AI; Smith, J; Ding, W; Zhao, C; Chohan, N; Okumura, M; Rosario, C; Ding, Y; Lindemuth, E; Bauer, AM; Bar, KJ; Ambrozak, D; Chao, CW; Chuang, G-Y; Geng, H; Lin, BC; Louder, MK; Nguyen, R; Zhang, B; Lewis, MG; Raymond, DD; Doria-Rose, NA; Schramm, CA; Douek, DC; Roederer, M; Kepler, TB; Kelsoe, G; Mascola, JR; Kwong, PD; Korber, BT; Harrison, SC; Haynes, BF; Hahn, BH; Shaw, GM

Published Date

  • January 8, 2021

Published In

Volume / Issue

  • 371 / 6525

PubMed ID

  • 33214287

Pubmed Central ID

  • PMC8040783

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.abd2638

Language

  • eng

Conference Location

  • United States