EMD-7459

Single-particle
3.8 Å
EMD-7459 Deposition: 08/02/2018
Map released: 16/05/2018
Last modified: 25/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-7459

Cryo-EM structure at 3.8 A resolution of vaccine-elicited antibody vFP20.01 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122

EMD-7459

Single-particle
3.8 Å
EMD-7459 Deposition: 08/02/2018
Map released: 16/05/2018
Last modified: 25/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human immunodeficiency virus 1
Sample: vFP20.01-BG505 DS-SOSIP-VRC03-PGT122
Fitted models: 6cde (Avg. Q-score: 0.443)

Deposition Authors: Acharya P , Carragher B, Potter CS, Kwong PD
Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.
PUBMED: 29867235
DOI: doi:10.1038/s41591-018-0042-6
ISSN: 1546-170X
Abstract:
A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.