Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains

Nat Commun. 2024 May 21;15(1):4301. doi: 10.1038/s41467-024-48514-8.

Abstract

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.

MeSH terms

  • AIDS Vaccines* / immunology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing* / immunology
  • Binding Sites
  • CD4 Antigens* / immunology
  • CD4 Antigens* / metabolism
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / immunology
  • Cryoelectron Microscopy
  • HIV Antibodies* / immunology
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1* / immunology
  • Humans
  • Vaccines, DNA / immunology