Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan.
AIDS Vaccines
/ genetics
Amino Acid Sequence
Antibodies, Monoclonal
/ genetics
Antibodies, Neutralizing
/ genetics
Antibody Affinity
B-Lymphocytes
/ immunology
Broadly Neutralizing Antibodies
/ genetics
CD4 Antigens
/ metabolism
Complementarity Determining Regions
/ genetics
HIV Antibodies
/ genetics
HIV Envelope Protein gp120
/ immunology
HIV Infections
/ immunology
HIV-1
/ physiology
Humans
Polysaccharides
/ metabolism
Protein Binding
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
16 07 2019
16 07 2019
Historique:
received:
20
11
2018
revised:
31
03
2019
accepted:
06
06
2019
entrez:
18
7
2019
pubmed:
18
7
2019
medline:
18
12
2019
Statut:
ppublish
Résumé
The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ∼24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.
Identifiants
pubmed: 31315032
pii: S1074-7613(19)30249-3
doi: 10.1016/j.immuni.2019.06.004
pmc: PMC6642152
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
CD4 Antigens
0
Complementarity Determining Regions
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
Polysaccharides
0
VRC01 monoclonal antibody
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
141-154.e6Subventions
Organisme : NIAID NIH HHS
ID : P30 AI036214
Pays : United States
Organisme : NIAID NIH HHS
ID : R00 AI120851
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068618
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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