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[Science] 광범위 HIV 중화 항체발견으로 백신 개발 기대
작성자
홍기종
작성일
2009-09-06
조회
2043

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

Laura M. Walker 1{dagger}, Sanjay K. Phogat 2{dagger}*, Po-Ying Chan-Hui 3, Denise Wagner 2, Pham Phung 4,Julie L. Goss 4, Terri Wrin 4, Melissa D. Simek 5, Steven Fling 1, Jennifer L. Mitcham 3,Jennifer K. Lehrman 5, Frances H. Priddy 5, Ole A. Olsen 3, Steven M. Frey 3, Phillip W. Hammond 3,Protocol G Principal Investigators {dagger}, Stephen Kaminsky 2, Timothy Zamb 2, Matthew Moyle 3,Wayne C. Koff 5, Pascal Poignard 1, Dennis R. Burton 6*

1 Department of Immunology and Microbial Science, and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
2 Design Lab, International AIDS Vaccine Initiative, New York, NY 11226, USA.
3 Theraclone Sciences, Seattle, WA 98104, USA.
4 Monogram Biosciences, Inc., South San Francisco, CA 94080, USA.
5 International AIDS Vaccine Initiative, New York, NY 10038, USA.
6 Department of Immunology and Microbial Science, and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Techonology, and Harvard, Boston, MA 02114, USA.
 

* To whom correspondence should be addressed.
Sanjay K. Phogat , E-mail: SPhogat@iavi.org
Dennis R. Burton , E-mail: burton@scripps.edu
 

 

{dagger}These authors contributed equally to this work. 

{dagger}Protocol G Principal Investigators are listed at the end of the paper. 

Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1–infected individuals, define criticalepitopes 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 approximately 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.