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Publication Abstract from PubMed

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.

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.,Williams WB, Alam SM, Ofek G, Erdmann N, Montefiori DC, Seaman MS, Wagh K, Korber B, Edwards RJ, Mansouri K, Eaton A, Cain DW, Martin M, Hwang J, Arus-Altuz A, Lu X, Cai F, Jamieson N, Parks R, Barr M, Foulger A, Anasti K, Patel P, Sammour S, Parsons RJ, Huang X, Lindenberger J, Fetics S, Janowska K, Niyongabo A, Janus BM, Astavans A, Fox CB, Mohanty I, Evangelous T, Chen Y, Berry M, Kirshner H, Van Itallie E, Saunders KO, Wiehe K, Cohen KW, McElrath MJ, Corey L, Acharya P, Walsh SR, Baden LR, Haynes BF Cell. 2024 May 14:S0092-8674(24)00459-8. doi: 10.1016/j.cell.2024.04.033. PMID:38761800^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.