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Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target

2009; American Association for the Advancement of Science; Volume: 326; Issue: 5950 Linguagem: Inglês

10.1126/science.1178746

1095-9203

Laura M. Walker, Sanjay Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa Simek, Steven P. Fling, Jennifer L. Mitcham, Jennifer Lehrman, Frances Priddy, Ole Olsen, Steven M. Frey, Phillip W. Hammond, Protocol G. Principal Investigators, Stephen M. Kaminsky, Timothy J. Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, Dennis R. Burton,

Hepatitis C virus research

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.