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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)
Related entries: 8g8a, 8g8c

Cited: 6 times
EuropePMC logo PMID: 38761800

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.

Reviews citing this publication (4)

  1. Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1. Walimbwa SI, Maly P, Kafkova LR, Raska M. J Biomed Sci 31 83 (2024)
  2. Cryo-electron microscopy in the study of virus entry and infection. Dutta M, Acharya P. Front Mol Biosci 11 1429180 (2024)
  3. HIV Vaccine Development at a Crossroads: New B and T Cell Approaches. Govindan R, Stephenson KE. Vaccines (Basel) 12 1043 (2024)
  4. Human Immunodeficiency Virus Vaccine: Promise and Challenges. Graciaa DS, Walsh SR, Rouphael N. Infect Dis Clin North Am 38 475-485 (2024)

Articles citing this publication (2)

  1. The CH1 domain influences the expression and antigen sensing of the HIV-specific CH31 IgM-BCR and IgG-BCR. Ortiz Y, Anasti K, Kane AP, Cronin K, Alam SM, Reth M. Proc Natl Acad Sci U S A 121 e2404728121 (2024)
  2. Alpaca-derived nanobody targeting the hydrophobic pocket of the HIV-1 gp41 NHR broadly neutralizes HIV-1 by blocking six-helix bundle formation. Sun L, Chen B, Liu X, Zhu Y, Zhang G, Liang X, Xing L, Xu W, Jiang S, Wang X. Curr Res Microb Sci 7 100263 (2024)


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