Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 38761800.
- Also identified by DOI 10.1016/j.cell.2024.04.033 and PMC identifier 11993910.
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Abstract
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.
Medical subject headings
- AIDS Vaccines
- HIV-1
- Antibodies, Neutralizing
- B-Lymphocytes
- HIV Antibodies