National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI100148
米国
Bill & Melinda Gates Foundation
INV-002143
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P50 1U54AI170856
米国
引用
ジャーナル: NPJ Vaccines / 年: 2024 タイトル: Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer. 著者: Andrew T DeLaitsch / Jennifer R Keeffe / Harry B Gristick / Juliet A Lee / Wenge Ding / Weimin Liu / Ashwin N Skelly / George M Shaw / Beatrice H Hahn / Pamela J Björkman / 要旨: Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing ...Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure. Env trimers bound by Ab1456 adopted conformations resembling CD4-bound open Env states in the absence of soluble CD4, whereas trimers bound by Ab1271 exhibited a trimer apex-altered conformation to accommodate antibody binding. The finding that elicited antibodies cross-neutralized by targeting altered, non-closed, prefusion Env trimer conformations provides important information about Env dynamics that is relevant for HIV-1 vaccine design aimed at raising antibodies to desired epitopes on closed pre-fusion Env trimers.