8VH3

CH505.M5.G458Y CE2 Design SOSIP

Summary for 8VH3

• Entry DOI: 10.2210/pdb8vh3/pdb
• EMDB information: 43233
• Descriptor: CH505.CE2 SOSIP gp120, CH505.CE2 SOSIP gp41 (2 entities in total)
• Functional Keywords: immunogen, vaccine, antibody, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 204173.13

Authors

Henderson, R.,Acharya, P. (deposition date: 2023-12-30, release date: 2024-10-02, Last modification date: 2024-11-13)

Primary citation

Henderson, R.,Anasti, K.,Manne, K.,Stalls, V.,Saunders, C.,Bililign, Y.,Williams, A.,Bubphamala, P.,Montani, M.,Kachhap, S.,Li, J.,Jaing, C.,Newman, A.,Cain, D.W.,Lu, X.,Venkatayogi, S.,Berry, M.,Wagh, K.,Korber, B.,Saunders, K.O.,Tian, M.,Alt, F.,Wiehe, K.,Acharya, P.,Alam, S.M.,Haynes, B.F.
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.
Nat Commun, 15:9503-9503, 2024

PubMed 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.

PubMed: 39489734
DOI: 10.1038/s41467-024-53120-9

Experimental method

ELECTRON MICROSCOPY (3.9 Å)