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Originally published in Science Express on 3 September 2009
Science 9 October 2009:
Vol. 326. no. 5950, pp. 285 - 289
DOI: 10.1126/science.1178746
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Reports

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

Laura M. Walker,1,* Sanjay K. Phogat,2,*,{ddagger} 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. Burton1,6,{ddagger}

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.

1 Department of Immunology and Microbial Science, and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
2 AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative, New York, NY 11220, 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 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA 02114, USA.

* These authors contributed equally to this work.

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

{ddagger} To whom correspondence should be addressed. E-mail: burton{at}scripps.edu (D.R.B.); SPhogat{at}iavi.org (S.K.P.)

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