Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 04 2023
08 04 2023
Historique:
received:
03
10
2022
accepted:
29
03
2023
medline:
11
4
2023
entrez:
8
4
2023
pubmed:
9
4
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37031217
doi: 10.1038/s41467-023-37742-z
pii: 10.1038/s41467-023-37742-z
pmc: PMC10082823
doi:
Substances chimiques
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Antibodies, Neutralizing
0
Vaccines
0
Polysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1985Subventions
Organisme : NIAID NIH HHS
ID : P01 AI124337
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129698
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140844
Pays : United States
Informations de copyright
© 2023. The Author(s).
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