Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization

Sci Immunol. 2026 Feb 13;11(116):eadz5064. doi: 10.1126/sciimmunol.adz5064. Epub 2026 Feb 13.

Abstract

Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multiboost regimens. In rhesus macaques, simian-human immunodeficiency virus (SHIV) infection rapidly drives the development of some bnAb classes sharing structural similarities with those in humans. Here, we generated a knockin (KI) mouse model with B cells bearing the unmutated common ancestor of a V2 apex-targeted bnAb lineage, V033-a. A single immunization with a germline-targeting native-like trimer, Q23-APEX-GT1, recapitulated the ontogeny of the mature rhesus bnAb in KI mice, including rare, disfavored somatic mutations. Resulting antibodies exhibited potent neutralization against a broad panel of heterologous HIV-1 strains. Boosting with Env escape mutant trimers further improved breadth and potency, and cryo-electron microscopy analysis revealed the structural basis for heterologous neutralization breadth. Nonhuman primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV vaccination regimens.

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / immunology
  • Disease Models, Animal
  • Gene Knock-In Techniques
  • HIV Antibodies* / immunology
  • HIV Infections* / immunology
  • HIV-1* / immunology
  • Humans
  • Immunization
  • Macaca mulatta
  • Mice

Substances

  • HIV Antibodies
  • Antibodies, Neutralizing