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, 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, G Miiro, J Serwanga, A Pozniak, D McPhee, O Manigart, L Mwananyanda, E Karita, A Inwoley, W Jaoko, J DeHovitz, L G Bekker, P Pitisuttithum, R Paris, S Allen, 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, 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, G Miiro, J Serwanga, A Pozniak, D McPhee, O Manigart, L Mwananyanda, E Karita, A Inwoley, W Jaoko, J DeHovitz, L G Bekker, P Pitisuttithum, R Paris, S Allen
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.
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Source: PubMed