In the basement of the Vaccine Research Center (VRC) at Yerkes’ Main Station at the end of Gatewood Road live thousands of rats, mice, and voles. Their tiny claws scrape the bottoms of stacked, ventilated cages, through which one can glimpse the rodents’ translucent ears, hairless tails, and twitching noses.

While it might seem like a storeroom for the NBC challenge series Fear Factor, which calls on contestants to face their phobias, this sterile environment of glass and steel is actually the place at Emory where most clinical vaccine trials begin: the vivarium.

Not that the vivarium doesn’t have its own dangers. Its sophisticated ventilation and decontamination systems are necessary to comply with Biosafety Level 3 standards for researchers who study infectious agents like HIV and malaria.

While primates have received much of the publicity, especially at Yerkes, rodents are still the most common animals used in biomedical research, due to their rapid maturation and high breeding capacity. Federal law mandates that the safety and efficacy of experimental drugs and vaccines be tested in animals prior to undertaking human trials.

“The order is generally mice to monkeys to humans,” says Rafi Ahmed, professor of microbiology and immunology and director of the VRC.

Since its inception in 1995, the Vaccine Research Center, with twenty-three state-of-the-art laboratories and a cadre of internationally known researchers, was conceived as a “one-stop” shop, where experimental vaccines developed on-site could also be tested. Last year, with the opening of the VRC’s Hope Clinic on Church Street in downtown Decatur, this vision was realized. The Hope Clinic is the first facility in the country dedicated solely to testing vaccines in clinical human trials.

The first Hope vaccine trial began in February—fourteen volunteers were given a new HIV vaccine developed by Merck, one of the largest pharmaceutical vaccine manufacturers in the world.

“Atlanta seems to be a receptive place to do HIV vaccine trials. The community here really wants to make a difference,” says Mark Feinberg, director of the clinic.

Merck chose Emory as one of eight test sites in the country for phase one trials of its experimental AIDS vaccine, which was developed from selected proteins of HIV rather than the whole virus and is designed to elicit a targeted immune response. One of a new breed of DNA-based vaccines, it does not prevent infection but reduces or eliminates viral particles in the body. DNA vaccines can be manufactured inexpensively in a shorter period of time than conventional vaccines and are less fragile.

Developing a safe, effective, and affordable vaccine to prevent HIV infection is the Vaccine Research Center’s primary goal, Ahmed says. AIDS vaccines have been especially hard to develop because of the nature of the virus, which destroys the very immune cells a vaccine enlists.

“HIV is constantly changing and mutating, so it presents a moving target, essentially,” Ahmed says. “You have to understand both the virus and the immune system to develop an effective vaccine.”

Another promising DNA-based AIDS vaccine, developed at Emory by Harriet Robinson and colleagues Rama Rao Amara and James Smith, will be moving into human trials this year, after showing success in primate trials. The multiprotein vaccine requires three shots–two DNA-based inoculations to prime the immune system, followed by a booster.

Many other experimental vaccines are being developed at Emory’s VRC as well, to combat diseases including malaria, measles, herpes, and influenza.

Robinson, Ted Ross, and researcher Yan Xu have successfully engineered and tested a single-dose, DNA-based influenza vaccine in mice, which could serve as a model for more effective vaccines against a variety of viruses, including HIV. Since new strains of the influenza virus are constantly emerging, guarding against a flu epidemic with conventional vaccines involves anticipating the next strain. But DNA vaccines could be made quickly enough to be distributed after the specific influenza strain is identified.

The Bill and Melinda Gates Foundation has awarded a three-year, $885,000 grant to Robinson’s lab to support her ongoing research to develop a DNA-based vaccine for measles. Robinson is collaborating with Diane Griffin of Johns Hopkins University and Paul Rota of the Centers for Disease Control and Prevention (CDC).

Measles kill about 900,000 people a year and remains endemic in many developing countries because children either do not receive the vaccine or they receive it too early. If a child is younger than fifteen months, maternal antibodies are so plentiful in his or her blood that the measles vaccine antibodies fail to develop. Robinson and her team are working with rhesus monkeys to develop DNA measles vaccines that are effective in the first year of life.

Another worldwide killer is malaria, which is carried and spread by mosquitoes and infects three hundred million to five hundred million people a year. It is prevalent in tropical regions, including parts of Africa, Southeast Asia, South America, Central America, and India. Mary R. Galinski, a VRC investigator and assistant professor in the infectious disease division of the School of Medicine, and Yerkes scientist Alberto Moreno are conducting trials in primates to assess the safety, dosing, and effectiveness of several malaria vaccines. Galinski is also studying the genetic and biological make-up of plasmodium, the organism that causes malaria.

Samuel H. Speck, director of the Center for Emerging Infectious Diseases, is investigating herpesviruses and the Epstein-Barr virus. A major property of herpesviruses is their ability to persist for life. Speck is trying to determine how these viruses avoid their victim’s immune response and how they “reactivate” after long periods of latency.

The VRC’s research is funded by an array of private and governmental grants, including the Georgia Research Alliance (GRA), the CDC, the National Institutes of Health, and the Gates Foundation. Funding totalled $18 million last year and is expected to be even higher this year. The GRA also provides funds for salaries–Ahmed is the GRA Eminent Scholar in Vaccine Research and Speck is the GRA Eminent Scholar in Emerging Infectious Diseases.

The VRC has established its own start-up company, GeoVax, through which it will eventually be able to market its vaccines. In the near future, Ahmed says, VRC scientists will be working toward vaccines for hepatitis C and certain types of cancer.

“In research and academia,” he says, “we are always looking to move forward.”

To find out more about Emory’s Vaccine Research Center, go to

www.emory.edu/WHSC/YERKES/VRC/.