By Lisa Seachrist

Washington Editor

WASHINGTON — With an FDA go-ahead, VaxGen, Inc.'s AIDSVax will be the first vaccine designed to prevent HIV to enter into large scale Phase III clinical trials.

The South San Francisco-based spin-off from Genentech Inc. expects to begin inoculations with the vaccine at five sites in the U.S. this month. In addition, VaxGen intends to begin a Phase III trial in Thailand this fall upon receiving permission from the FDA and the Thai Health Ministry.

"We really see this as the beginning of the end of the AIDS epidemic," said VaxGen spokesperson Donna Walters. "VaxGen has a commitment to end this epidemic."

The company will test the vaccine in 5,000 Americans who are at high risk of becoming infected with HIV — primarily gay men and the uninfected partners of AIDS patients. The Thai study will test the vaccine in 2,500 intravenous drug users.

The vaccine uses recombinant versions of a protein called glycoprotein 120 (gp120) from two different strains of HIV. GP120 is a major envelope protein from HIV that smuggles the virus into immune cells.

The vaccine is intended to produce antibodies that would stymie HIV's ability to infect immune cells. The American formulation will contain versions of gp120 from the predominant strains of HIV found in North America, Western Europe and Australia. The Thai vaccine will come from strains predominant in South Asia.

"We suspect that the vaccines will offer protection to more than just two strains of HIV," Walters said. She noted the company also will work on creating vaccines appropriate for use in the African subcontinent where the epidemic began.

The move to a pivotal clinical trial is a significant turnaround in HIV vaccine development. In June 1994, the National Institutes of Health (NIH) decided to shelve plans to fund a Phase III trial of gp120 vaccines after funding Phase I and Phase II studies of vaccines developed by Genentech and Chiron Corp., of Emeryville, Calif.

The NIH's National Institute of Allergy and Infectious Diseases concluded the data from those trials simply weren't promising enough to justify funding a large scale trial of the vaccines.

Company Betting Bivalent Version More Effective

In February 1996, Genentech formed VaxGen to take control of the gp120 project and see the endeavor through Phase III trials. Robert Nowinski took over as chairman of the new company and Donald Francis, who eradicated the smallpox virus in India when he worked with the Centers for Disease Control and who led the Genentech gp120 effort, became president of the company, which is housed on Genentech's campus. Initially, the new firm was called Genenvax. (See BioWorld Today, Feb. 21, 1996, p. 1.)

The difference between the vaccines tested by NIH and the VaxGen product is that the original vaccines contained a single version of gp120. VaxGen is betting that a bivalent version of the vaccine will boost its effectiveness.

However, because HIV infects the immune system itself, many scientists have voiced skepticism that antibodies alone could protect against HIV infections.

"This is tried and true science — we know generating antibodies can protect against infections," Walters said.

Walters also pointed out that during the 1950s many people said the Salk vaccine was too ineffective to prevent polio. Nevertheless, the vaccine spared hundreds of thousands of children in the seven years before the more effective Sabin vaccine became available.

"We know people develop antibodies against HIV with this vaccine, we know it is safe, the time has come to test it to see if it is effective," Walters said.

Chiron took a different tack with vaccine research., collaborating with Pasteur Merieux Connaught, of Lyon, France, to develop a number of different HIV vaccines. Those vaccines are currently in Phase I and II studies, and they are at least a year away from a Phase III trial.

The Immune Response Corp. of Carlsbad, Calif., currently has an HIV vaccine, Remune, in a three-year Phase III study, which began in March 1996. Remune is designed as a therapy for people already infected with HIV and the trial's data safety and monitoring board is meeting this month to assess interim results from the study. *

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