两大顶级研究所《Science》发布最具前途的HIV靶标

【字体: www.ebiotrade.com 时间:2009年09月07日 来源:生物通

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  生物通报道,来自顶级研究所Scripps研究所和纽约国际AIDS疫苗研究所的科学家联手在《Science》在线版发布HIV研究新进展文章Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target,发现两个最具价值的靶标。

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生物通报道,来自顶级研究所Scripps研究所和纽约国际AIDS疫苗研究所的科学家联手在《Science》在线版发布HIV研究新进展文章Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target,发现两个最具价值的靶标。

 

应用高通量培养系统,2研究所的科学家们在一个HIV感染的非洲捐赠者体内辨识出了2种过去未被认识的抗体。 这些抗体看来具有非常强效的中和HIV病毒的作用,它们还比其它已知的广谱中和抗体能够中和范围更广的来自许多不同亚型的HIV病毒。

 

研究人员说,这些新发现的广谱中和抗体的作用就像是一个能打开某一隐藏的病毒之锁的钥匙,它们能够识别一个保守的HIV蛋白上的一个蛋白质基序,而这种基序是研究人员过去所没有描述过的。 他们说,这些抗体和新的蛋白基序的发现可能会为人们打开令人深感兴趣的未来HIV疫苗研发的新标靶之门。

(生物通 小茜)

生物通推荐原文摘要

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

Laura M. Walker 1, Sanjay K. Phogat 2*, 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 , 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.

Abstract

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 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.

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