Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

被引：219

作者：

Dosenovic, Pia ^{[1
]}

von Boehmer, Lotta ^{[1
]}

Escolano, Amelia ^{[1
]}

Jardine, Joseph ^{[3
,10
,11
]}

Freund, Natalia T. ^{[1
]}

Gitlin, Alexander D. ^{[1
]}

McGuire, Andrew T. ^{[4
]}

Kulp, Daniel W. ^{[3
,10
,11
]}

Oliveira, Thiago ^{[1
]}

Scharf, Louise ^{[5
]}

Pietzsch, John ^{[1
]}

Gray, Matthew D. ^{[4
]}

Cupo, Albert ^{[6
]}

van Gils, Marit J. ^{[7
]}

Yao, Kai-Hui ^{[1
]}

Liu, Cassie ^{[1
]}

Gazumyan, Anna ^{[1
,2
]}

Seaman, Michael S. ^{[8
]}

Bjoerkman, Pamela J. ^{[2
,5
]}

Sanders, Rogier W. ^{[6
]}

Moore, John P. ^{[6
]}

Stamatatos, Leonidas ^{[4
,9
]}

Schief, William R. ^{[3
,10
,11
,12
]}

Nussenzweig, Michel C. ^{[1
,2
]}

机构：

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

[2] Scripps Res Inst, Howard Hughes Med Inst, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[4] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[5] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[6] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA

[7] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[8] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

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

[10] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[11] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[12] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

来源：

CELL | 2015年 / 161卷 / 07期

基金：

欧洲研究理事会; 瑞典研究理事会; 加拿大健康研究院;

关键词：

B-CELL RECEPTORS; ENVELOPE TRIMER; SOMATIC HYPERMUTATION; VACCINE; VIRUS; GP120; SITE; RECOMBINATION; GLYCOPROTEIN; AFFINITY;

D O I：

10.1016/j.cell.2015.06.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.

引用

页码：1505 / 1515

页数：11

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