EMD-44246
Cryo-EM structure of HIV-1 JRFL v6 Env in complex with vaccine-elicited, Membrane Proximal External Region (MPER) directed antibody DH1317.4.
EMD-44246
Single-particle6.7 Å
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Map released: 14/08/2024
Last modified: 14/08/2024
Sample Organism:
Homo sapiens
Sample: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
Deposition Authors: Acharya P
,
Parsons R,
Janowska K,
Williams WB,
Alam M,
Haynes BF
Sample: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
Deposition Authors: Acharya P
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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
(2024) Cell , 187 , 2919 - 2934.e20
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(2024) Cell , 187 , 2919 - 2934.e20
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.
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.