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

Science. 2021 Jan 8;371(6525):eabd2638. doi: 10.1126/science.abd2638. Epub 2020 Nov 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Binding Sites
  • Biological Coevolution / immunology*
  • Broadly Neutralizing Antibodies* / chemistry
  • Broadly Neutralizing Antibodies* / genetics
  • Broadly Neutralizing Antibodies* / immunology
  • CD4 Antigens / immunology
  • Cryoelectron Microscopy
  • Epitopes / immunology
  • HIV Antibodies* / chemistry
  • HIV Antibodies* / genetics
  • HIV Antibodies* / immunology
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Macaca mulatta
  • Molecular Mimicry / immunology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • Virus Replication


  • Broadly Neutralizing Antibodies
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120