Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.

Autor: Zhang YN; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Paynter J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Antanasijevic A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA., Allen JD; School of Biological Sciences, Highfield Campus, University of Southampton, Southampton, SO17 1BJ, UK., Eldad M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Lee YZ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Copps J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA., Newby ML; School of Biological Sciences, Highfield Campus, University of Southampton, Southampton, SO17 1BJ, UK., He L; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Chavez D; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Frost P; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Goodroe A; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Dutton J; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Lanford R; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Chen C; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Crispin M; School of Biological Sciences, Highfield Campus, University of Southampton, Southampton, SO17 1BJ, UK., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA., Zhu J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. jiang@scripps.edu.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. jiang@scripps.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 08; Vol. 14 (1), pp. 1985. Date of Electronic Publication: 2023 Apr 08.
DOI: 10.1038/s41467-023-37742-z
Abstrakt: Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. For 1c-SApNPs, glycan trimming improves recognition of the CD4 binding site without affecting broadly neutralizing antibodies (bNAbs) to major glycan epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increases the frequency of vaccine responders (FVR) and steers antibody responses away from immunodominant glycan holes and glycan patches. The mechanism of vaccine-induced immunity is examined in mice. Compared with the UFO trimer, the multilayered E2p and I3-01v9 1c-SApNPs show 420 times longer retention in lymph node follicles, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions. These findings can inform future HIV-1 vaccine development.
(© 2023. The Author(s).)
Databáze: MEDLINE
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