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


Walker, LM; Phogat, SK; Chan-Hui, PY; Wagner, D; Phung, P; Goss, JL; Wrin, T; Simek, MD; Fling, S; Mitcham, JL; Lehrman, JK; Priddy, FH; Olsen, OA; Frey, SM; Hammond, PW; Protocol G Principal Investigators (Miiro G, Serwanga J, Pozniak, McPheeD; Manigart, O; Mwananyanda L, Karita E, Inwoley A, Jaoko W, Dehovitz J, Bekker ; Kaminsky, S; Zamb, T; Moyle, M; Koff, WC; Poignard, P; Burton, DR; (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science (New York, NY), 326 (5950). pp. 285-9. ISSN 0036-8075 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Vaccine Centre
PubMed ID: 19729618
Web of Science ID: 270599500042
URI: http://researchonline.lshtm.ac.uk/id/eprint/2007

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