Caltech scientists show why anti-HIV antibodies are ineffective at blocking...(ch of a b12 or 4E10 antibody--the spans ...)

"HIV may have evolved a way to escape one of the main strategies our immune system uses to defeat infections," says Klein. "Based on these data, it seems that the virus is circumventing the bivalent effect that is so key to the potency of antibodies."

"I consider this a very important paper because it changes the focus of the discussion about why anti-HIV antibodies are so poor," adds virologist David Baltimore, the Robert Andrews Millikan Professor of Biology and a Nobel Prize winner. "It brings attention to a long-recognized but often forgotten aspect of antibody attack--that they attack with two heads. What this paper shows is that anti-HIV antibodies are restricted to using one head at a time and that makes them bind much less well. Responding to this newly recognized challenge will be difficult because it identifies an intrinsic limitation on the effectiveness of almost any natural anti-HIV antibodies."

In addition to Bjorkman and Klein, the authors on the PNAS paper, "Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10," are Caltech research technicians Priyanthi Gnanapragasam, Rachel Galimidi, and Christopher Foglesong, and senior research specialist Anthony West, Jr.

The work described in the paper was supported by a Bill and Melinda Gates Foundation Grant through the Grand Challenges in Global Health Initiative and the Collaboration for AIDS Vaccine Discovery.

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