Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.
DH270.6
HIV
bnAb
immunogen
improbable mutations
vaccine
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
17 08 2021
17 08 2021
Historique:
received:
01
03
2021
revised:
25
05
2021
accepted:
28
07
2021
entrez:
18
8
2021
pubmed:
19
8
2021
medline:
10
2
2022
Statut:
ppublish
Résumé
Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. In this study, we identify a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interact with DH270.6-like antibodies containing this set of key mutations are identified and selected in vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and they establish rational approaches to identify boosting candidate immunogens.
Identifiants
pubmed: 34407396
pii: S2211-1247(21)00995-5
doi: 10.1016/j.celrep.2021.109561
pmc: PMC8493474
mid: NIHMS1734084
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
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
Pagination
109561Subventions
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144371
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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