In the year 2000, an estimated 5.3 million people were newly infected with HIV, and researchers around the country struggled to find an HIV vaccine. From San Francisco to Boston to Durham, the struggle continues as researchers try to find a way to either prevent or contain the virus.
At the University of California at San Francisco, Dr. James Kahn, associate clinical professor of medicine and associate director of the AIDS program at San Francisco General Hospital, is currently receiving funding from VaxGen, a private company devoted to the prevention and eradication of the HIV virus. The company says it has the only vaccine that has made it to human testing. The vaccine is called GP120, because it consists of a glycoprotein with 120 amino acids.
The vaccine mimics the outer envelope of HIV, so when an antibody binds to the vaccine's coating, it should elicit an immune response as though it were reacting to the virus itself.
VaxGen is currently testing the vaccine on 5,400 people in the United States and Canada and 2,500 people in Thailand. Most of the subjects are high-risk for contracting HIV-the pool consists primarily of female prostitutes and gay men who regularly engage in unsafe sex.
The subjects will be monitored regularly over the next several years to see if the vaccine will prevent them from becoming infected with HIV. VaxGen is using a North American-Thai strain of the virus, and if the vaccine proves effective, the company will begin working on vaccines to prevent other strains.
In Boston, Dr. Norman Letvin, professor of medicine at Harvard University, is using funding from the National Institutes of Health to develop another potential vaccine. In studies of both people and monkeys, he has found that a specific type of T-cell lymphocyte is capable of killing HIV-infected cells.
"We've seen that when these lymphocytes are eliminated from the immune system, there is a massive increase in the replication of the HIV virus," Letvin said. "The reverse happens when more lymphocytes were present in the system." Letvin's vaccine consists of inoculated DNA and peptides of HIV.
In developing this type of vaccine, Letvin says he is trying to contain HIV-not to prevent infection from occurring. "Right now, if a person has the HIV virus, there will be a high level of viral replication, but with this drug the replication itself could be dramatically contained," he said. "If you can't prevent the infection, you can at least try to control it and allow the infected person to live a longer, more productive life."
Back at Duke, Dr. Bart Haynes, Frederic M. Hanes professor of medicine, has been researching an HIV vaccine at Duke for 15 years. For the last 10 years, he and his team have received grants from the National Institute of Allergies and Infectious Diseases.
Haynes' team-which includes Dr. Herman Staats, an assistant research professor in the division of rheumatology and immunology-is focusing on developing a vaccine administered via nasal spray. Their work is based on a earlier report, which showed that many sub-Saharan African prostitutes had become immune to HIV. Building on the results of that study, the team is trying to create a vaccine that will induce both mucosal and systemic responses to block HIV.
Both Haynes and Staats said the potential vaccine, which also mimics HIV's envelope, will stimulate antibodies and cytotoxic T-cells to fight at the mucosal surface. It will also enhance a generalized immune system response to the virus.
By exposing the mucosal surfaces in the nose to the vaccine, researchers hope that the response at the mucosal surface of the genital region-the area most likely to first come into contact with the virus-will also be stimulated to fight the infection. Acting as a second line of defense, the systemic response should kill the infection if the mucosal response fails to contain it. The vaccine's biological structure mimics the outer envelope of the virus, so when an antibody binds to the envelope, it should elicit an immune response as though it were reacting to the virus itself.
"We have gotten outstanding results from our mouse studies," said Staats. "In the next few months we'll be moving onto the next step, which is testing the vaccine on primates." The team is also beginning to establish connections with investigators in sub-Saharan Africa and Zambia, so that they can begin working on vaccines for strains specific to those regions.
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