EMD-41361

Single-particle
3.2 Å
EMD-41361 Deposition: 26/07/2023
Map released: 28/08/2024
Last modified: 15/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-41361

CRYO-EM STRUCTURE OF HIV-1 BG505DS-SOSIP.664 ENV TRIMER BOUND TO DJ85-e.01 FAB

EMD-41361

Single-particle
3.2 Å
EMD-41361 Deposition: 26/07/2023
Map released: 28/08/2024
Last modified: 15/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: BG505 DS-SOSIP DJ85-e.01 FAB COMPLEX
Fitted models: 8tl4

Deposition Authors: Pletnev S, Hoyt F, Fischer E, Kwong P
Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.
PUBMED: 39471811
DOI: doi:10.1016/j.cell.2024.10.003
ISSN: 1097-4172
Abstract:
An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID50] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%-60% (50% inhibitory concentration [IC50] < 50 μg/mL) and total lineage-concentrations estimates of 50-200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.