据9月4日的《科学》杂志报道说,在大约20年的时间中,人们第一次发现了新的可中和HIV的广谱性抗体;这一发现产生了某些令人兴奋的研发疫苗的新标靶。 Laura Walker及其同僚应用高通量培养系统在一个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分化枝(或群体)的病毒。
Science DOI: 10.1126/science.1178746 September 3, 2009
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.
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.