This is the third installment of a biweekly series appearing throughout the semester exploring different aspects of the Medical Center's fight against AIDS.

This story describes the continuing search for an AIDS vaccine. The next installment will appear Oct. 22.

Dozens of physicians and health policy activists caught the nation's attention last month by publicly volunteering to be injected with a weakened form of live HIV to help researchers develop a vaccine against AIDS.

Would-be participants in the trials, sponsored by the International Association of Physicians in AIDS Care, hope the vaccine, which was developed at Harvard Medical School and has shown promising results in monkeys, will work equally well in humans. Their bold stance caused many to wonder just how far researchers had come in the long search for a vaccine against AIDS.

The IAPAC announcement occurred less than six months after the challenge President Bill Clinton issued in May to find an AIDS vaccine by 2008 and focused media attention on AIDS vaccine research for the second time this year. The Medical Center has been at the forefront of this research for the last five years, according to Dr. Barton Haynes, Frederic M. Hanes Professor of Medicine.

Haynes' laboratory is one of about 10 labs around the country to house a National Cooperative Vaccine Development Group Grant-a project from the National Institutes of Health, Haynes said, that forms part of the government's coordinated effort to find a vaccine for AIDS.

Preliminary human trials are currently underway on a prototype vaccine developed by the lab, Haynes explained, but the Duke vaccine is very different from the one that the IAPAC seeks to test. Instead of using weak but complete copies of HIV to provoke a response from the body's immune system, the Haynes lab's potential vaccine consists of a mix of short pieces of the virus' protein coat. Without any viral genetic material, the vaccine cannot become infectious.

Haynes said that work on the vaccine, known as C4-V3, was influenced by the discovery of the so-called V3 loop, a location on the outside of the virus that is a frequent binding site for anti-HIV antibodies. The V3 loop was first singled out as a target for drugs in the mid-1980s, following its discovery at the Medical Center by Haynes and Dani Bolognesi, James B. Duke Professor of Experimental Surgery.

But the initial enthusiasm generated by the discovery of the V3 loop ebbed, Bolognesi explained, as researchers realized it was not nearly as prominent a target among the many strains of HIV found outside the laboratory. The challenge facing Haynes' lab now is to develop a vaccine that works against more than just lab specimens.

"HIV is not one organism, but a whole swarm of variants," Haynes said. "A lab-attenuated vaccine works for only one variant." He said he and his colleagues have been able to address this problem by taking snippets of protein from four different types of HIV and combining them into one vaccine package-a technique the Medical Center is pioneering.

Although there are many more than four HIV strains, noted Dr. John Bartlett, associate professor of medicine in the Division of Infectious Diseases, combining peptide fragments from four strains should be enough to protect against two-thirds of the strains present in North America.

Bartlett is the principal investigator in a study running clinical trials to test how effective the C4-V3 vaccine is. "It appeared to be very promising in animal studies in terms of immune response," he said, "and we wanted to study it in humans to establish that it was safe."

So far, Bartlett said, the prototype has been tested on 10 HIV-positive patients to determine whether it produces the desired immune response without overwhelming side effects, and tests are now set to begin on HIV-negative volunteers. Results of the trial are still being reviewed.

The challenge facing researchers is to find a balance between a vaccine that is strong enough to be useful and safe enough to be practical, Haynes said.

Herman Staats, assistant research professor of medicine and immunology, is working on developing a method by which patients may be given an HIV vaccine so that antibodies are produced in the areas of the body where they are needed most. Since HIV is spread mostly across mucous membranes-the type of membrane that lines the mouth, reproductive tract and anus-Staats said that one of his most important concerns is promoting an immune response in these areas.

He added that preliminary research with mice and guinea pigs has been "very promising," as it has demonstrated that vaccines taken through the nose produce a response in the mucous membranes, and he said he thinks the inter-nasal route of immunization is the biggest part of his work.

Despite this progress in the lab, even the most promising vaccine tests have not yet been proven effective in preventing the disease in a single human. The mysteries of the HIV virus have perplexed scientists for almost two decades and those expecting instant results will almost certainly have to wait at least a little longer.