HIV This Week

Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target. Walker LM, Phoga SK, Chan-Hui P-Y, 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, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DL. Science. Published online September 3, 2009. Science DOI: 10.1126/science.1178746

Broadly neutralizing antibodies, which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, Walker and colleagues examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and selected donors for monoclonal antibody generation. They used a high-throughput neutralization screen of antibody-containing culture supernatants from approximately 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent monoclonal antibodies 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 broadly neutralizing antibody responses.

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Editors’ note: The two novel broadly neutralising antibodies described here are the first to be discovered in more than a decade and the first to be isolated from a donor in sub-Saharan Africa. They not only target multiple strains of HIV, i.e. they are broadly neutralising, but they are very potent, binding tightly to the virus and working at minute levels compared to previously discovered neutralising antibodies. As well, they reveal a new vulnerable easier-to-reach spot on the virus that no previously known antibody targets. The unusual features of these two monoclonal antibodies provide exciting new leads for the design of HIV vaccines that would stimulate the body to make potent antibodies that would be active against a broad range of strains of the virus when a person is exposed to the virus.