Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

Cell. 2024 Jun 6;187(12):2919-2934.e20. doi: 10.1016/j.cell.2024.04.033. Epub 2024 May 17.


A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

MeSH terms

  • AIDS Vaccines* / immunology
  • Antibodies, Neutralizing* / immunology
  • B-Lymphocytes* / immunology
  • Cell Lineage
  • HIV Antibodies* / immunology
  • HIV Envelope Protein gp41 / immunology
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1* / immunology
  • Humans
  • Liposomes
  • Mutation
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • Liposomes
  • env Gene Products, Human Immunodeficiency Virus
  • HIV Envelope Protein gp41