Advances Inject Hope Into Quest for Vaccine

Moreover, any experimental AIDS vaccine worth its sting will leave volunteers awash in HIV antibodies, which means they will test positive on an AIDS test even if they do not have AIDS. That could wreak havoc with efforts to gain employment, insurance, or visas for travel to countries that demand evidence of HIV status.

Even Lynch, who works as a case manager at a local agency that distributes emergency financial aid to people with AIDS, had second thoughts when he came in for the first of three scheduled inoculations. "There was a brief moment of anxiety," he conceded. "But I've had a couple of very close friends who have contracted HIV in the past few years," he said softly. "If it helps get us even one step closer to a vaccine, then it's well worth it."

In his office overlooking the St. Louis University campus, Belshe recalled his involvement in previous vaccine efforts, which ultimately led to the development of highly effective vaccines for measles, whooping cough and a fatal kind of childhood influenza. The challenge of creating an AIDS vaccine is unlike any other he has faced, he said.

HIV's uncanny knack for mutation makes it a constantly moving target, said Belshe, who heads the AIDS Vaccine Evaluation Group, an NIH-funded network of research sites in six U.S. cities. Making matters worse, the virus infects the very immune system cells that are meant to attack it -- the cells a vaccine is designed to rally.

Then there is the still unanswered question of what, exactly, a vaccine ought to do to elicit a state of protective immunity. Is it enough, for example, that a vaccine produce anti-HIV antibodies in the blood? Doubts seem justifiable; HIV-positive people make antibodies by the billions without any obvious therapeutic benefit.

Some scientists believe that the problem with antibodies is mostly one of timing; antibodies made in response to an infection may appear too late to do much good, while a vaccine-induced arsenal of antibodies, ready to strike at the very first sign of infection, might protect a person from AIDS.

Then again, antibodies may simply not be up to the task of tackling HIV. In that case, scientists may have to concentrate on vaccines that stimulate the other major branch of the body's armed forces: fierce immune system cells called killer T-cells.

"It's going to require several field trials of different types of vaccines to find out," Belshe said.

The usual approach to answering such basic scientific questions is to conduct studies in animals. But here, too, HIV has been uncooperative. The virus does not infect mice or monkeys, the workhorses of basic biological research. And although chimpanzees can be infected with HIV, they do not become sick for at least a decade -- making them only marginally more useful than human beings in studies of vaccine efficacy.

So it is that researchers have called upon an ever growing number of human volunteers to help them test experimental AIDS vaccines. To date, more than 2,000 healthy volunteers in the United States have participated in about 40 small clinical trials.

The process has been a study in disappointment, and AIDS vaccine researchers repeatedly have had to lower their expectations. The idea of creating a vaccine that would not only prevent new infections but would also be therapeutic in people already infected with HIV has mostly dropped by the wayside, for example. With the exception of one or two companies banking on the long shot of therapeutic vaccination, everyone trying to develop an AIDS vaccine is now focusing on prevention.

Even the goal of completely preventing HIV infection -- what scientists call "sterilizing immunity" -- is not considered achievable, at least for now. The current aim is to make a vaccine that can muffle the normally rampant viral multiplication that occurs soon after infection -- the "viremia" through which a small platoon of viruses in a few drops of semen or blood blossoms into a florid infection. The hope is that the body will be able to keep the few remaining viruses suppressed, and symptoms at bay, for many years and perhaps indefinitely.