Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies

被引：104

作者：

McGuire, Andrew T. ^{[1
]}

Dreyer, Anita M. ^{[1
]}

Carbonetti, Sara ^{[1
]}

Lippy, Adriana ^{[1
]}

Glenn, Jolene ^{[1
]}

Scheid, Johannes F. ^{[2
]}

Mouquet, Hugo ^{[3
,4
]}

Stamatatos, Leonidas ^{[1
,5
]}

机构：

[1] Seattle Biomed Res Inst, Seattle, WA 98109 USA

[2] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[3] Inst Pasteur, Dept Immunol, Lab Humoral Response Pathogens, F-75015 Paris, France

[4] CNRS, URA 1961, F-75015 Paris, France

[5] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA

来源：

SCIENCE | 2014年 / 346卷 / 6215期

基金：

加拿大健康研究院; 瑞士国家科学基金会;

关键词：

B-CELL RECEPTORS; STRUCTURAL BASIS; EPITOPE; DESIGN; BINDING; VIRUS; GP120; LINES; SITE;

D O I：

10.1126/science.1259206

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.

引用

页码：1380 / 1383

页数：4

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