Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base

• DOI: 10.1016/j.celrep.2021.108937
• Publication Date: 2021-04-06T15:39:40Z
• Authors: Angela R. Corrigan; Hongying Duan; Cheng Cheng; Christopher A. Go...; Li Ou; Kai Xu; Megan E. DeMouth; Hui Geng; Sandeep Narpala; Sarah O’Connell; Baoshan Zhang; Tongqing Zhou; Manjula Basappa; Jeffrey C. Boyington; Steven J. Chen; Sijy O’Dell; Amarendra Pegu; Tyler Stephens; Yaroslav Tsybovsky; Jelle van Schooten; John P. Todd; Shuishu Wang; Nicole A. Doria-Rose; Kathryn E. Foulds; Richard A. Koup; Adrian B. McDermott; Marit J. van Gils; Peter D. Kwong; John R. Mascola
• Keywords: Trimer; Conjugate; Priming (agriculture)

Soluble "SOSIP"-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high-titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate effect base of priming with immunogens targeting fusion peptide (FP) site vulnerability, here, we quantify prevalence trimer-base antibody in 49 non-human primates immunized various SOSIP-stabilized Env and FP-carrier conjugates. Trimer-base account for ∼90% overall response animals only, ∼70% a cocktail SOSIP FP conjugate, ∼30% primed conjugates before immunization. Notably, neutralization breadth FP-conjugate-primed correlates inversely responses. Our data provide methods to reveal that FP-conjugate priming, either alone or as part cocktail, can reduce improve outcome.