HIV-1 infections with multiple founders associate with the development of neutralization breadth.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
18
10
2021
accepted:
16
02
2022
revised:
30
03
2022
pubmed:
19
3
2022
medline:
2
4
2022
entrez:
18
3
2022
Statut:
epublish
Résumé
Eliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort. Half of the individuals who developed bnAbs were infected with multiple HIV-1 founder variants, whereas all individuals with limited neutralization breadth had been infected with single HIV-1 founders. Accordingly, at HIV-1 diagnosis, env diversity was significantly higher in participants who later developed bnAbs compared to those with limited breadth (p = 0.012). This association between founder multiplicity and the subsequent development of neutralization breadth was also observed in 56 placebo recipients in the RV144 vaccine efficacy trial. In addition, we found no evidence that neutralization breath was heritable when analyzing env sequences from the 126 participants. These results demonstrate that the presence of slightly different HIV-1 variants in acute infection could promote the induction of bnAbs, suggesting a novel vaccine strategy, whereby an initial immunization with a cocktail of minimally distant antigens would be able to initiate bnAb development towards breadth.
Identifiants
pubmed: 35303045
doi: 10.1371/journal.ppat.1010369
pii: PPATHOGENS-D-21-02097
pmc: PMC8967031
doi:
Substances chimiques
Antibodies, Neutralizing
0
Epitopes
0
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010369Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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