New fundamental discoveries have been made about the immune defenses of a rare group of HIV patients whose bodies can naturally keep the virus at bay. By detailing the molecular workings of so-called broadly neutralizing anti-HIV antibodies, researchers at Rockefeller University hope that their work will ultimately enable them to similarly arm those who are not equipped with exceptional immunological firepower. HIV strains mutate rapidly, making them notoriously evasive targets for the immune system. In particular, the HIV envelope spike, called gp160, is the site of a host of mutations that obstruct the few elements that all of the virus strains share. Prior research has shown that only 4 super antibodies block the activity of that protein in a broad range of HIV strains, neutralizing the virus. But all attempts to coax the human body into producing those 4 have failed. In experiments published in Nature last year, the researchers showed that a diverse group of broadly neutralizing antibodies cloned from 433 B cells of 6 slow progressing HIV patients were as capable of knocking down a broad range of HIV strains as any one of the super antibodies. The ability to isolate and clone antibodies from B cells was first worked out by the researchers in a pioneering 2003 paper in Science. Now, having applied that method to the B cells in HIV patients with high titers of broadly neutralizing antibodies, the new research explores in more detail what their antibodies target and how they attack. This particular cadre of polyreactive antibodies takes a long time (years) to develop in slow progressing HIV patients, and much remains to be discovered about the process, but the researchers believe that a vaccine designed to elicit antibodies that mimic these properties could be a promising strategy to beat the deadly virus.
(Source: Rockefeller University Newswire, September 30, 2010)
