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

Science  09 Oct 2009:
Vol. 326, Issue 5950, pp. 285-289
DOI: 10.1126/science.1178746

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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 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.

  • * These authors contributed equally to this work.

  • Protocol G Principal Investigators are listed at the end of the manuscript.

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