Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Science. 2024 May 17;384(6697):eadj8321. doi: 10.1126/science.adj8321. Epub 2024 May 17.


Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

MeSH terms

  • AIDS Vaccines* / immunology
  • Animals
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies* / immunology
  • Complementarity Determining Regions* / immunology
  • Cryoelectron Microscopy
  • Germinal Center* / immunology
  • HIV Antibodies* / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Macaca mulatta
  • Memory B Cells / immunology
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • AIDS Vaccines
  • Broadly Neutralizing Antibodies
  • Complementarity Determining Regions
  • env Gene Products, Human Immunodeficiency Virus
  • HIV Antibodies
  • Immunoglobulin Heavy Chains