TY - JOUR
T1 - HIV-1 infections with multiple founders associate with the development of neutralization breadth
AU - Lewitus, Eric
AU - Townsley, Samantha M.
AU - Li, Yifan
AU - Donofrio, Gina C.
AU - Dearlove, Bethany L.
AU - Bai, Hongjun
AU - Sanders-Buell, Eric
AU - O Sullivan, Anne Marie
AU - Bose, Meera
AU - Kibuuka, Hannah
AU - Maganga, Lucas
AU - Nitayaphan, Sorachai
AU - Sawe, Fredrick K.
AU - Eller, Leigh Anne
AU - Michael, Nelson L.
AU - Polonis, Victoria R.
AU - Ake, Julie A.
AU - Vasan, Sandhya
AU - Robb, Merlin L.
AU - Tovanabutra, Sodsai
AU - Krebs, Shelly J.
AU - Rolland, Morgane
N1 - Publisher Copyright:
© 2022 Public Library of Science. All rights reserved.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85127418998&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1010369
DO - 10.1371/journal.ppat.1010369
M3 - Article
C2 - 35303045
AN - SCOPUS:85127418998
SN - 1553-7366
VL - 18
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 3
M1 - e1010369
ER -