Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
Walker, Laura M;
Phogat, Sanjay K;
Chan-Hui, Po-Ying;
Wagner, Denise;
Phung, Pham;
Goss, Julie L;
Wrin, Terri;
Simek, Melissa D;
Fling, Steven;
Mitcham, Jennifer L;
+12 more...Lehrman, Jennifer K;
Priddy, Frances H;
Olsen, Ole A;
Frey, Steven M;
Hammond, Phillip W;
Protocol G Principal Investigators;
Kaminsky, Stephen;
Zamb, Timothy;
Moyle, Matthew;
Koff, Wayne C;
Poignard, Pascal;
Burton, Dennis R;
(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: https://doi.org/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.