In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 3 ( 2022-3-18), p. e1010369-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010369
DOI:
10.1371/journal.ppat.1010369.g001
DOI:
10.1371/journal.ppat.1010369.g002
DOI:
10.1371/journal.ppat.1010369.g003
DOI:
10.1371/journal.ppat.1010369.g004
DOI:
10.1371/journal.ppat.1010369.t001
DOI:
10.1371/journal.ppat.1010369.s001
DOI:
10.1371/journal.ppat.1010369.s002
DOI:
10.1371/journal.ppat.1010369.s003
DOI:
10.1371/journal.ppat.1010369.s004
DOI:
10.1371/journal.ppat.1010369.s005
DOI:
10.1371/journal.ppat.1010369.s006
DOI:
10.1371/journal.ppat.1010369.s007
DOI:
10.1371/journal.ppat.1010369.s008
DOI:
10.1371/journal.ppat.1010369.s009
DOI:
10.1371/journal.ppat.1010369.s010
DOI:
10.1371/journal.ppat.1010369.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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