Advances Inject Hope Into Quest for Vaccine
By Rick Weiss
ST. LOUIS Inside a small and nearly windowless downtown medical clinic, Tim Lynch rolls up one sleeve of his T-shirt and looks straight ahead, trying not to notice the stainless steel needle being unsheathed beside him.
Lynch, who is 35 and gay, is not infected with HIV, the virus that causes AIDS. But if all goes well in the next few weeks his body will behave very much as though it were.
St. Louis University vaccine researcher Robert Belshe leans forward, slides the needle into Lynch's arm and pushes the plunger on the syringe, propelling about a million specially modified viruses into the man's muscle.
They are canarypox viruses, which cause disease in birds but are harmless in people. Each one has been genetically engineered to contain three extra genes that are normally found only in HIV. The goal is to introduce some of the hallmarks of HIV to Lynch's immune system, so he can build up a SWAT team of antibodies and white blood cells capable of fighting off a real infection, should one ever occur.
Lynch is one of thousands of healthy people in the United States who have agreed to lease their immune systems to science for a period of months or years, as part of the quest to develop an AIDS vaccine. It is a quest that has proven exceedingly and unexpectedly difficult.
AIDS vaccine researchers have endured so many disappointments in the past decade that some began to think their mission was impossible. HIV has shrugged off dozens of experimental formulations that almost certainly would have felled lesser viruses. Meanwhile, progress has been hampered by a lack of investment from private vaccine developers and a federal research program criticized as lacking in leadership.
Yet a new, if cautious, optimism has emerged among many AIDS vaccine researchers in the past year or so. Using salvaged bits of information from otherwise failed experiments, scientists have been developing a picture of what a successful AIDS vaccine would look like then building and testing vaccines along those lines and getting them into human trials. Increasingly, the results of those trials have been offering up more good news than bad.
Political and economic will may also be on the rise. This summer, President Clinton declared a national goal of producing an effective AIDS vaccine within 10 years. He also called for the quick creation of a vaccine research center at the National Institutes of Health.
"It's still not going to be easy," said Patricia Fast, associate director of the vaccine and prevention research program of the National Institute for Allergy and Infectious Diseases, the NIH branch that holds primary responsibility for the federal war against AIDS. "But the idea that it's impossible," Fast said, "is gone."
The need for an AIDS vaccine has never been greater. Although new and potent drugs are proving remarkably effective in many patients, scientists are concerned that those benefits may not last forever. And the new drugs are largely unavailable or unaffordable in developing countries, where 95 percent of the world's new cases are emerging.
"We'll never end this epidemic unless we have a vaccine," said Sandra Thurman, chairman of the White House Office of National AIDS Policy.
Recent progress notwithstanding, the art and science of making a vaccine remains frustratingly inexact and the testing process remains fraught with dangers. In Lynch's case, for example, no one knows whether the engineered bird virus might someday make him or his fellow volunteers ill. Also worrisome: Animal studies have suggested that AIDS vaccines may in some cases speed, rather than slow, the progression of AIDS in vaccinated people who eventually become infected with HIV.
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.
© 1997 The Washington Post Company