EMD-44246

Single-particle
6.7 Å
EMD-44246 Deposition: 23/03/2024
Map released: 14/08/2024
Last modified: 14/08/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

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-particle
6.7 Å
EMD-44246 Deposition: 23/03/2024
Map released: 14/08/2024
Last modified: 14/08/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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
Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.
PUBMED: 38761800
DOI: doi:10.1016/j.cell.2024.04.033
ISSN: 1097-4172
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.