EMD-41810

Single-particle
4.25 Å
EMD-41810 Deposition: 31/08/2023
Map released: 03/01/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-41810

Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env Local Refinement

EMD-41810

Single-particle
4.25 Å
EMD-41810 Deposition: 31/08/2023
Map released: 03/01/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Macaca mulatta, Human immunodeficiency virus 1
Sample: The complex of vaccine elicited CD4 binding site neutralizing antibody DH1285 Fab with CH505M5chimer.6R.SOSIP.664v4.1 Env
Fitted models: 8u1d (Avg. Q-score: 0.359)

Deposition Authors: Thakur B , Stalls VD, Acharya P
Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
PUBMED: 38181743
DOI: doi:10.1016/j.cell.2023.12.002
ISSN: 1097-4172
Abstract:
The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.