Another chink in HIV's armor may point the way to a vaccine

Representation of the 5 sites of vulnerability on the HIV-1 envelope glycoprotein trimer, including the newly discovered PGT151 (red)--Courtesy of Christina Corbaci and Andrew Ward, The Scripps Research Institute.

A weakness in the HIV virus exposed by scientists at the Scripps Research Institute and the International AIDS Vaccine Initiative (IAVI) may provide clues for designing a much-sought HIV vaccine.

Recent HIV vaccine work has focused on a small set of patients whose immune systems generated rare antibodies able to overcome most strains of the deadly virus. Many researchers believe that an effective vaccine against HIV would work by eliciting antibodies to a specific conserved site on the virus called V1V2, one of a handful of sites that remain constant on the fast-mutating virus.

This discovery highlights a new site on the HIV virus that could be attacked by such antibodies to neutralize the infectivity of a wide variety of HIV strains.

"HIV has very few known sites of vulnerability, but in this work we've described a new one, and we expect it will be useful in developing a vaccine," said Dennis Burton, a professor in Scripps Research Institute's department of immunology and microbial science. Burton is also the scientific director of IAVI's Neutralizing Antibody Center and of the U.S. National Institutes of Health's Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery on Scripps' La Jolla campus.

The findings were reported in two papers appearing in the May issue of the journal Immunity.

Previously, scientists had discovered four spots of vulnerability, all of them located on HIV's only exposed surface antigen, the flowerlike envelope (Env) protein (gp140) that sprouts from the viral membrane and is designed to grab and penetrate host cells. These vulnerable spots on the HIV virus can be difficult to target because HIV generally conceals these sites under a thick layer of sugars and fast-mutating parts of the virus surface. Much of a person's antibody response goes toward fighting the fast-mutating parts, meaning it's only partly effective.

The researchers say the discovery of the new site, called PGT151, hints at the possibility that other vulnerable sites on the HIV virus may exist.

- read the study abstracts here and here
- see the press release