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Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Publication ,  Journal Article
Henderson, R; Anasti, K; Manne, K; Stalls, V; Saunders, C; Bililign, Y; Williams, A; Bubphamala, P; Montani, M; Kachhap, S; Li, J; Jaing, C ...
Published in: bioRxiv
December 30, 2023

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. To precisely engineer bnAb boosting immunogens, we used 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 identified Env mutations that were predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encoded antibody affinity gains and selected 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.

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bioRxiv

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Publication Date

December 30, 2023

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United States
 

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Henderson, R., Anasti, K., Manne, K., Stalls, V., Saunders, C., Bililign, Y., … Haynes, B. F. (2023). Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies. BioRxiv. https://doi.org/10.1101/2023.12.15.571700
Henderson, Rory, Kara Anasti, Kartik Manne, Victoria Stalls, Carrie Saunders, Yishak Bililign, Ashliegh Williams, et al. “Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.BioRxiv, December 30, 2023. https://doi.org/10.1101/2023.12.15.571700.
Henderson R, Anasti K, Manne K, Stalls V, Saunders C, Bililign Y, et al. Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies. bioRxiv. 2023 Dec 30;
Henderson, Rory, et al. “Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.BioRxiv, Dec. 2023. Pubmed, doi:10.1101/2023.12.15.571700.
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, Lu X, Venkatayogi S, Berry M, Wagh K, Korber B, Saunders KO, Tian M, Alt F, Wiehe K, Acharya P, Alam SM, Haynes BF. Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies. bioRxiv. 2023 Dec 30;

Published In

bioRxiv

DOI

Publication Date

December 30, 2023

Location

United States