Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target

被引：1429

作者：

Walker, Laura M. ^{[2
,3
]}

Phogat, Sanjay K. ^{[1
]}

Chan-Hui, Po-Ying ^{[4
]}

Wagner, Denise ^{[1
]}

Phung, Pham ^{[5
]}

Goss, Julie L. ^{[5
]}

Wrin, Terri ^{[5
]}

Simek, Melissa D. ^{[6
]}

Fling, Steven ^{[2
,3
]}

Mitcham, Jennifer L. ^{[4
]}

Lehrman, Jennifer K. ^{[6
]}

Priddy, Frances H. ^{[6
]}

Olsen, Ole A. ^{[4
]}

Frey, Steven M. ^{[4
]}

Hammond, Phillip W. ^{[4
]}

Kaminsky, Stephen ^{[1
]}

Zamb, Timothy ^{[1
]}

Moyle, Matthew ^{[4
]}

Koff, Wayne C. ^{[6
]}

Poignard, Pascal ^{[2
,3
]}

Burton, Dennis R. ^{[2
,3
,7
,8
]}

机构：

[1] Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, New York, NY 11220 USA

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

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

[4] Theraclone Sci, Seattle, WA 98104 USA

[5] Monogram Biosci Inc, San Francisco, CA 94080 USA

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

[7] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA

[8] Harvard Univ, Boston, MA 02114 USA

来源：

SCIENCE | 2009年 / 326卷 / 5950期

关键词：

SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; MONOCLONAL-ANTIBODIES; PASSIVE TRANSFER; V2; DOMAIN; GP120; ENVELOPE; PROTECTION; MACAQUES; EPITOPE; DESIGN;

D O I：

10.1126/science.1178746

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), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.

引用

页码：285 / 289

页数：5

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