Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
26
02
2021
accepted:
16
06
2021
entrez:
29
7
2021
pubmed:
30
7
2021
medline:
10
8
2021
Statut:
epublish
Résumé
Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process.
Identifiants
pubmed: 34321200
pii: 7/31/eabh2791
doi: 10.1126/sciadv.abh2791
pmc: PMC8318364
pii:
doi:
Substances chimiques
AIDS Vaccines
0
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136621
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
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