HIV-1 infections with multiple founders associate with the development of neutralization breadth

Eric Lewitus, Samantha M. Townsley, Yifan Li, Gina C. Donofrio, Bethany L. Dearlove, Hongjun Bai, Eric Sanders-Buell, Anne Marie O Sullivan, Meera Bose, Hannah Kibuuka, Lucas Maganga, Sorachai Nitayaphan, Fredrick K. Sawe, Leigh Anne Eller, Nelson L. Michael, Victoria R. Polonis, Julie A. Ake, Sandhya Vasan, Merlin L. Robb, Sodsai TovanabutraShelly J. Krebs, Morgane Rolland

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article numbere1010369
JournalPLoS Pathogens
Volume18
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

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