EMD-45943

Single-particle
6.3 Å
EMD-45943 Deposition: 26/07/2024
Map released: 11/12/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-45943

Ab1271 Fab-bound 6535.3 SOSIP.664 trimer

EMD-45943

Single-particle
6.3 Å
EMD-45943 Deposition: 26/07/2024
Map released: 11/12/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human immunodeficiency virus 1
Sample: HIV-1 6535.3 SOSIP.664 in complex with a single copy of Ab1271 Fab

Deposition Authors: DeLaitsch AT , Bjorkman PJ
Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer.
DeLaitsch AT , Keeffe JR, Gristick HB, Lee JA, Ding W, Liu W, Skelly AN, Shaw GM, Hahn BH, Bjorkman PJ
(2024) NPJ Vaccines , 9 , 240 - 240
PUBMED: 39638818
DOI: doi:10.1038/s41541-024-01038-0
ISSN: 2059-0105
Abstract:
Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure. Env trimers bound by Ab1456 adopted conformations resembling CD4-bound open Env states in the absence of soluble CD4, whereas trimers bound by Ab1271 exhibited a trimer apex-altered conformation to accommodate antibody binding. The finding that elicited antibodies cross-neutralized by targeting altered, non-closed, prefusion Env trimer conformations provides important information about Env dynamics that is relevant for HIV-1 vaccine design aimed at raising antibodies to desired epitopes on closed pre-fusion Env trimers.