Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
07 03 2022
07 03 2022
Historique:
received:
01
10
2021
revised:
03
01
2022
accepted:
12
01
2022
entrez:
1
3
2022
pubmed:
2
3
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
Identifiants
pubmed: 35230385
pii: 213042
doi: 10.1084/jem.20212045
pmc: PMC8932546
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
Epitopes
0
HIV Antibodies
0
Immunoglobulin A
0
Immunoglobulin G
0
Polysaccharides
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
Pays : United States
Organisme : European Research Council
ID : ERC-2013-StG 337146
Pays : International
Informations de copyright
© 2022 Lorin et al.
Déclaration de conflit d'intérêts
Disclosures: F.A. Rey is a board member of EureKARE and MELETIUS Therapeutics. No other disclosures were reported.
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