HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
30
10
2019
accepted:
08
04
2020
entrez:
18
6
2020
pubmed:
18
6
2020
medline:
18
6
2020
Statut:
epublish
Résumé
To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole-dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole-specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A 3.5-Å cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.v5.2 trimer demonstrated that while the epitope recognized overlapped the N332 glycan supersite by contacting the GDIR motif at the base of V3, primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway.
Identifiants
pubmed: 32548265
doi: 10.1126/sciadv.aba0512
pii: aba0512
pmc: PMC7274786
doi:
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
Pagination
eaba0512Subventions
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Informations de copyright
Copyright © 2020 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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