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

Autor:	Henderson R; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Anasti K; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Manne K; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Stalls V; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Saunders C; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Bililign Y; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Williams A; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Bubphamala P; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Montani M; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Kachhap S; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Li J; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Jaing C; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Newman A; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Cain DW; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Lu X; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Venkatayogi S; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Berry M; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Wagh K; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Korber B; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.; The New Mexico Consortium, Los Alamos, NM, USA., Saunders KO; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Surgery, Duke University Medical Center, Durham, NC, USA., Tian M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Alt F; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Wiehe K; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Acharya P; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Surgery, Duke University Medical Center, Durham, NC, USA.; Department of Biochemistry, Duke University, Durham, NC, USA., Alam SM; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Haynes BF; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA. barton.haynes@duke.edu.; Department of Immunology, Duke University Medical Center, Durham, NC, USA. barton.haynes@duke.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Nov 03; Vol. 15 (1), pp. 9503. Date of Electronic Publication: 2024 Nov 03.
DOI:	10.1038/s41467-024-53120-9
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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