A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch

Elife. 2020 Oct 21;9:e61991. doi: 10.7554/eLife.61991.

Abstract

A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.

Keywords: anti hiv-1; antibody; broadly neutralizing; immunology; infectious disease; inflammation; microbiology; patch antibody; rhesus macaque; v3 glycan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Broadly Neutralizing Antibodies / immunology*
  • Female
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • Macaca mulatta
  • Peptide Fragments / immunology*
  • Polysaccharides / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Broadly Neutralizing Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Polysaccharides