The Food and Drug Administration has approved the Emory Vaccine Center’s application to begin a Phase I clinical trial of its multiprotein AIDS vaccine. Pending final approval of the trial by institutional review boards, 30 human volunteers at three sites around the country will begin receiving the vaccine within the next several months.

Emory’s AIDS vaccine consists of two components: a DNA prime and a recombinant poxvirus as a booster. The vaccine is designed to promote a memory immune response against the three major proteins (Gag, Pol, Env) expressed by HIV.

The first clinical trial will assess the safety of the vaccine’s DNA priming component using three groups of volunteers at the University of Alabama-Birmingham, the University of California at San Francisco and the University of Washington in Seattle. The trial will compare the effects of high and low dosages of the vaccine in two groups of (HIV negative) volunteers, who will receive two intramuscular injections. The third group will receive two injections of a placebo.

Preliminary results from the Phase I trial of the DNA component of the vaccine should be available by the middle of next year. A separate Phase I clinical trial of the booster is expected to begin within a year and will involve different sets of volunteers.

“Most likely we will have to have a third trial to test the combined regimen of the DNA and booster portions of the vaccine,” said Harriet Robinson, chief of the Yerkes Division of Microbiology and Immunology, who led the development of the vaccine.

Robinson is confident that the clinical trials will confirm the vaccine’s ability to promote long-term protection against HIV. In tests in 24 rhesus monkeys at Yerkes, the vaccine successfully contained a highly virulent hybrid of simian and human immunodeficiency viruses (SHIV).

Since the vaccinated monkeys were exposed to SHIV two years ago, protective immunity against the virus has continued to improve. According to a Yerkes study reported in the October 2002 edition of the Journal of Virology, levels of viral DNA in the monkeys have declined to the nearly undetectable levels characteristic of a small subset of HIV-infected people, termed long-term nonprogressors, who carry HIV but do not develop AIDS.
A California biotech company, ViCal, manufactured the priming components of the AIDS vaccine for the Phase I clinical trial from the DNA of clade B, the most common HIV subtype in North America and Western Europe. Stanford Research Institute, another contract company, and Yerkes have tested the vaccine’s safety in rabbits and rhesus macaques.

In late 2003, a Phase I clinical trial of a vaccine against clade AG, the most common HIV subtype found in West Africa, will be launched in the United States and then in Côte d’Ivoire (formerly the Ivory Coast). The Emory Vaccine Center’s Hope Clinic will serve as one of the clinical test sites for this trial.

Production of the vaccine against subtype AG will be overseen by GeoVax Inc., the startup company founded by Emory and the Vaccine Center for manufacture of the vaccine.

By late 2004, the Vaccine Center hopes to begin a Phase I trial of a trivalent vaccine incorporating the DNA from clades B, AG, and C. Subtype C is the most prevalent form of HIV in India and southern Africa.

Robinson projects that Phase III efficacy trials of the AIDS vaccine could begin in 2006. Unlike the much smaller Phase I and II clinical trials, several thousand volunteers will be recruited for the Phase III trial.

The HIV Vaccine Trials Network of the National Institute of Allergy and Infectious Diseases will fund the initial Phase I trials.