Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.
HIV envelope
neutralizing antibody
next-generation sequencing
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
19 03 2019
19 03 2019
Historique:
received:
07
08
2018
revised:
13
11
2018
accepted:
13
02
2019
pubmed:
17
3
2019
medline:
21
8
2019
entrez:
17
3
2019
Statut:
ppublish
Résumé
Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.
Identifiants
pubmed: 30876875
pii: S1074-7613(19)30074-3
doi: 10.1016/j.immuni.2019.02.008
pmc: PMC6555550
mid: NIHMS1523630
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Neutralizing
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Pagination
677-691.e13Subventions
Organisme : NIAID NIH HHS
ID : R01 AI131722
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI005024-17
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI005022-17
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008320
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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