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New Collection of Broadly Neutralizing Antibodies Described

What started as a trickle of new antibodies has become a steady downpour. In recent years, researchers have succeeded in isolating large numbers of broadly neutralizing antibodies from chronically HIV-infected individuals. Yesterday, on the opening day of the AIDS Vaccine 2011 conference in Bangkok, Thailand, Ian Wilson of IAVI’s Neutralizing Antibody Center at The Scripps Research Institute presented recently published data on a collection of 17 broadly neutralizing antibodies that he reported are "extremely potent." The collection of new antibodies are 10 times more potent than the recently isolated antibodies and 100 times more potent than the original handful of neutralizing antibodies, including b12, 2G12, and 4E10.

 

The newly isolated antibodies, referred to as the PGT series, all seem to be glycan dependent, according to Wilson, with some of the antibodies binding directly to the glycans that coat HIV. 2G12 is another glycan-targeting broadly neutralizing antibody, though Wilson said the new antibodies are more complex than 2G12.

Wilson and colleagues have purified all 17 PGT antibodies for crystallization. The Fab region of one of the antibodies, PGT 128, was analyzed in complex with an engineered, glycosylated gp120 outer domain, allowing Wilson and colleagues to determine the epitope targeted by the antibody. They found that PGT 128 bound to two sugars as well as to the third variable loop of HIV Envelope. "This is a pretty extensive epitope," he said.

Another antibody, PGT 145, targeted an epitope in the first and second variable loops in a manner similar to PG9, one of the first of the new generation of broadly neutralizing antibodies to be isolated.