EMD-43233

Single-particle
3.9 Å
EMD-43233 Deposition: 30/12/2023
Map released: 02/10/2024
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-43233

CH505.M5.G458Y CE2 Design SOSIP

EMD-43233

Single-particle
3.9 Å
EMD-43233 Deposition: 30/12/2023
Map released: 02/10/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1
Sample: HIV-1 ectodomain
Fitted models: 8vh3 (Avg. Q-score: 0.433)

Deposition Authors: Henderson R , Acharya P
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.
PUBMED: 39489734
DOI: doi:10.1038/s41467-024-53120-9
ISSN: 2041-1723
Abstract:
Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identify Env mutations predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encode antibody affinity gains and select for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.