‘Tat’ protein advances AIDS vaccine search

Rhesus monkeys immunized with an inactivated HIV protein called Tat toxoid showed markedly lower viral levels following infection with simian HIV, according to a report in this week’s on-line issue of the U.S. Proceedings of the National Academy of Sciences.

The study implies that the modified human protein should be added to current candidates for HIV vaccines and represents an important new direction in vaccine development.

“This research solidifies our belief that Tat toxoid plays a key role in inhibiting viral pathogenesis of HIV,” says Robert Gallo, director of the Institute for Human Virology in Baltimore. “We believe that Tat toxoid needs to be included in therapeutic or preventive HIV vaccines.”

Research teams led by David Pauza at UW–Madison and Daniel Zagury at the Université Pierre et Marie Curie in Paris collaborated with Institute scientists on the project. The study involved rhesus monkeys from the Wisconsin Regional Primate Research Center, one of eight primate centers in the country supported by the National Institutes of Health.

Because of the close relationship between HIV and a monkey-human combination of the virus, called simian/human immunodeficiency virus, or SHIV, rhesus monkeys have become a preferred model for scientists seeking an AIDS vaccine.

Earlier work from the laboratories of Gallo, Zagury, and others revealed that a protein called Tat, made in HIV-infected cells, is secreted during infection and contributes to viral spread and immune system destruction in humans.

In the current study, researchers chemically manipulated human Tat into inactivated Tat toxoid, immunized the monkeys and challenged them with SHIV. The test vaccine induced a strong immune response and blocked the damaging effects on host cells from the unaltered Tat in the virus. These defenses, in turn, led to a significant decrease of virus at the onset of infection.

Similar data from researchers in Rome, Italy, were reported in Nature Medicine.