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Miiro G, Serwanga J, Pozniak A, McPhee D, Manigart O, Mwananyanda L, Karita E, Inwoley A, Jaoko W, DeHovitz J, Bekker LG, Pitisuttithum P, Paris R, Allen S.
Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, 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 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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