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

被引：15

作者：

Corrigan, Angela R. ^{[1
]}

Duan, Hongying ^{[1
]}

Cheng, Cheng ^{[1
]}

Gonelli, Christopher A. ^{[1
]}

Ou, Li ^{[1
]}

Xu, Kai ^{[1
]}

DeMouth, Megan E. ^{[1
]}

Geng, Hui ^{[1
]}

Narpala, Sandeep ^{[1
]}

O'Connell, Sarah ^{[1
]}

Zhang, Baoshan ^{[1
]}

Zhou, Tongqing ^{[1
]}

Basappa, Manjula ^{[1
]}

Boyington, Jeffrey C. ^{[1
]}

Chen, Steven J. ^{[1
]}

O'Dell, Sijy ^{[1
]}

Pegu, Amarendra ^{[1
]}

Stephens, Tyler ^{[2
]}

Tsybovsky, Yaroslav ^{[2
]}

van Schooten, Jelle ^{[3
]}

Todd, John P. ^{[1
]}

Wang, Shuishu ^{[1
]}

Doria-Rose, Nicole A. ^{[1
]}

Foulds, Kathryn E. ^{[1
]}

Koup, Richard A. ^{[1
]}

McDermott, Adrian B. ^{[1
]}

van Gils, Marit J. ^{[3
]}

Kwong, Peter D. ^{[1
]}

Mascola, John R. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Leidos Biomed Res Inc, Electron Microscopy Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21710 USA

[3] Univ Amsterdam, Amsterdam Inst Infect & Immun, Dept Med Microbiol, Amsterdam UMC, NL-1105 AZ Amsterdam, Netherlands

来源：

CELL REPORTS | 2021年 / 35卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CRYO-EM STRUCTURE; ANTIBODY-RESPONSES; ENV TRIMERS; NEUTRALIZATION; BROAD; SITE; EPITOPES; PROTEIN; DESIGN;

D O I：

10.1016/j.celrep.2021.108937

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 similar to 90% of the overall trimer response in animals immunized with trimer only, similar to 70% in animals immunized with a cocktail of SOSIP trimer and FP conjugate, and similar to 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.

引用

页数：16

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