Cell reports · 2021
Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод пока не подготовлен
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Corrigan Angela R, Duan Hongying, Cheng Cheng, Gonelli Christopher A, Ou Li, Xu Kai, DeMouth Megan E, Geng Hui, Narpala Sandeep, O'Connell Sarah, Zhang Baoshan, Zhou Tongqing, Basappa Manjula, Boyington Jeffrey C, Chen Steven J, O'Dell Sijy, Pegu Amarendra, Stephens Tyler, Tsybovsky Yaroslav, van Schooten Jelle, Todd John P, Wang Shuishu, VRC Production Program, Doria-Rose Nicole A, Foulds Kathryn E, Koup Richard A, McDermott Adrian B, van Gils Marit J, Kwong Peter D, Mascola John R
Аннотация
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 the effect on base responses of priming with immunogens targeting the fusion peptide (FP) site of vulnerability, here, we quantify the prevalence of trimer-base antibody responses in 49 non-human primates immunized with various SOSIP-stabilized Env trimers and FP-carrier conjugates. Trimer-base responses account for ∼90% of the overall trimer response in animals immunized with trimer only, ∼70% in animals immunized with a cocktail of SOSIP trimer and FP conjugate, and ∼30% in animals primed with FP conjugates before trimer immunization. Notably, neutralization breadth in FP-conjugate-primed animals correlates inversely with trimer-base responses. Our data provide methods to quantify the prevalence of trimer-base responses and reveal that FP-conjugate priming, either alone or as part of a cocktail, can reduce the trimer-base response and improve the neutralization outcome.