Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.

Laura M Walker; Sanjay K Phogat; Po-Ying Chan-Hui; Denise Wagner; Pham Phung; Julie L Goss; Terri Wrin; Melissa D Simek; Steven Fling; Jennifer L Mitcham; +12 more... Jennifer K Lehrman; Frances H Priddy; Ole A Olsen; Steven M Frey; Phillip W Hammond; Protocol G Principal Investigators; Stephen Kaminsky; Timothy Zamb; Matthew Moyle; Wayne C Koff; Pascal Poignard; Dennis R Burton; (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science (New York, NY), 326 (5950). pp. 285-289. ISSN 0036-8075 DOI: 10.1126/science.1178746
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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.

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