A vaccine aimed against AIDS and developed at Yerkes, the Vaccine Research Center (VRC) and the Laboratory of Viral Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, recently began its Phase I clinical trial.

A total of 30 human volunteers will be enrolled at the University of Alabama at Birmingham, the University of Washington and the San Francisco Department of Public Health. The trial is funded by NIAID and is conducted by the HIV Vaccine Trials Network, located at the Fred Hutchinson Cancer Research Center in Seattle.

Developed by virologists Harriet Robinson, James Smith, Bernard Moss and Linda Wyatt, the vaccine strategy employs two different components: two inoculations of a DNA vaccine that primes the immune system to recognize HIV; and a subsequent booster vaccine based on a recombinant poxvirus. Neither component incorporates the actual virus; instead the vaccine produces the three major proteins expressed by HIV. In essence, the vaccine induces the immune system to respond to the distinguishing features of HIV so the system will respond to the actual virus should it appear.

This first clinical trial, which will last one year, will focus on assessing the safety of the DNA primer vaccine among HIV-negative volunteers, who will be randomly assigned to receive one of the following: high-dose vaccine, low-dose vaccine or placebo. A second, separate clinical trial will focus on the safety of the booster vaccine.

“We will have a third Phase I trial to test the combined regimen of the DNA and booster portions of the vaccine strategy,” said Robinson, who is chief of microbiology and immunology at Yerkes and a faculty member of the Vaccine Center.

As Robinson and her colleagues reported in Science in 2001, in a study involving 24 rhesus macaque monkeys, the prime-boost vaccine strategy successfully contained infection and prevented progression to AIDS. According to a subsequent Yerkes study reported in October 2002 in the Journal of Virology, levels of viral RNA and 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 are infected with HIV but do not develop AIDS.

“It is important to remember that this clinical trial represents the culmination of years of work in basic science and preclinical studies involving animal models that have greatly expanded our knowledge of immunology,” said VRC Director Rafi Ahmed. “Every new AIDS vaccine candidate that enters human studies brings us closer to understanding HIV and the human immune system—and to ending the worldwide AIDS pandemic.”

The experimental vaccine is licensed from Emory by GeoVax Inc., a company
founded by Emory and the VRC to manufacture the vaccine.