Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
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.
Roark, Ryan S., Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, et al. “Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.” Science 371, no. 6525 (January 8, 2021). https://doi.org/10.1126/science.abd2638.