Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex

被引：286

作者：

Sok, Devin ^{[1
,2
,3
,6
]}

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

Pauthner, Matthias ^{[1
,2
,3
]}

Julien, Jean-Philippe ^{[2
,3
,4
,8
,9
,10
]}

Saye-Francisco, Karen L. ^{[1
,2
,3
]}

Hsueh, Jessica ^{[1
,2
,3
]}

Briney, Bryan ^{[1
,2
,3
]}

Lee, Jeong Hyun ^{[2
,3
,4
]}

Le, Khoa M. ^{[1
,2
,3
]}

Lee, Peter S. ^{[4
]}

Hua, Yuanzi ^{[2
,3
,4
]}

Seaman, Michael S. ^{[11
]}

Moore, John P. ^{[12
]}

Ward, Andrew B. ^{[2
,3
,4
]}

Wilson, Ian A. ^{[2
,3
,4
,5
]}

Sanders, Rogier W. ^{[7
,12
]}

Burton, Dennis R. ^{[1
,2
,3
,13
,14
]}

机构：

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

[2] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA

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

[4] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[6] Int AIDS Vaccine Initiat, New York, NY 10038 USA

[7] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Lab Expt Virol,Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[8] Univ Toronto, Hosp Sick Children, Res Inst, Program Mol Struct & Funct, Toronto, ON M5G 0A4, Canada

[9] Univ Toronto, Dept Biochem, Toronto, ON M5G 0A4, Canada

[10] Univ Toronto, Dept Immunol, Toronto, ON M5G 0A4, Canada

[11] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[12] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

[13] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02142 USA

[14] Harvard Univ, Boston, MA 02142 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 49期

基金：

美国国家卫生研究院; 欧洲研究理事会; 加拿大健康研究院;

关键词：

HIV; broadly neutralizing antibodies; BG505; SOSIP; B cell; vaccine; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; BROADLY NEUTRALIZING ANTIBODIES; N-GLYCAN RECOGNITION; CONFORMATIONAL EPITOPE; BINDING-SITE; ENV TRIMERS; CD4; BINDING; B-CELLS; TYPE-1;

D O I：

10.1073/pnas.1415789111

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：

Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 mu g/mL. Overall, our results highlight the utility of BG505 SOSIP. 664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.

引用

页码：17624 / 17629

页数：6

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