Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
15
03
2023
accepted:
10
05
2023
medline:
3
7
2023
pubmed:
29
6
2023
entrez:
29
6
2023
Statut:
epublish
Résumé
Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design. The V3-glycan targeting bnAb lineage (PC39-1) was isolated from subtype C-infected IAVI Protocol C elite neutralizer, donor PC39, and is defined by the presence of multiple independent insertions in CDRH1 that range from 1-11 amino acids in length. Memory B cell members of this lineage are predominantly atypical in phenotype yet also span the class-switched and antibody-secreting cell compartments. Development of neutralization breadth occurred concomitantly with extensive recombination between founder viruses before each virus separated into two distinct population "arms" that evolved independently to escape the PC39-1 lineage. Ab crystal structures show an extended CDRH1 that can help stabilize the CDRH3. Overall, these findings suggest that early exposure of the humoral system to multiple related Env molecules could promote the induction of bnAbs by focusing Ab responses to conserved epitopes.
Identifiants
pubmed: 37384622
doi: 10.1371/journal.ppat.1011416
pii: PPATHOGENS-D-23-00486
pmc: PMC10309625
doi:
Substances chimiques
Broadly Neutralizing Antibodies
0
HIV Antibodies
0
Epitopes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011416Informations de copyright
Copyright: © 2023 Joyce et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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