AIDS Vaccine Testing Goes Overseas

But the science is daunting and subjects hard to come by. Scientists have been forced to travel to remote corners of the world to find communities where the infection rate is high enough to show results in a reasonable amount of time.

Thailand, where AIDS is a leading cause of death, has been among the most accommodating places. The NIH effort there involves two vaccines that individually have been disappointing in previous trials. One of them, developed by a once-revered scientist in the AIDS world, flopped spectacularly after an expensive test funded by private investors. The other showed little promise in early trials. Researchers cling to the hope that using them simultaneously will attack different aspects of the disease and prove effective.

Disappointing Trials

A vaccine is basically a trick: Take a germ or part of a germ, kill it or alter it so that it doesn't cause disease, then inject it into the body. The body thinks it is being attacked and produces an immune response that will protect it when it is exposed to the real thing.

But because HIV comes in 11 subtypes that constantly mutate, it must be treated differently. Enter Donald Francis, a longtime government researcher who is credited with helping to eradicate smallpox and develop vaccines for Ebola and hepatitis B. Francis had great credibility in the AIDS community. He was immortalized as an early hero in Randy Shilts's book "And the Band Played On" because he recognized the danger of AIDS long before it became an epidemic and argued forcefully for government action.

In 1982, he left public service to work for biotechnology giant Genentech Inc. and concentrate on AIDS full time.

His idea was to try to use the protein envelope that surrounds HIV to try to trick the body into thinking the whole virus had invaded it. When he injected it into a group of chimpanzees and then exposed them to HIV, they were protected. Francis then injected the cloudy liquid into his arm and became human research subject No. 1. There were no side effects, or none that he could notice. When he drew his blood he saw something promising -- a strong antibody response. Antibodies, proteins that form in response to invaders, typically protect a person against infection.

The big question was: Would that be enough to stop HIV infection?

Based on the preliminary trials, many scientists were skeptical. Nine of the 499 U.S. volunteers who had received Francis's vaccine subsequently became infected with HIV -- not from the vaccine but from later sexual exposure to the virus. While Francis was not concerned with those "breakthrough infections," other scientists were. "It is not the fact of breakthroughs that is so disturbing," John P. Moore of Cornell University's medical college said at an international AIDS conference in 1996. "It is the individual cases where there was a good vaccine response but infection occurred nonetheless." Researchers feared that the virus mutated so quickly that antibodies were ineffective against it.

Other scientists turned to a new technique, using snippets of the virus to promote a response from another part of the immune system, which activates "T-cells" instead of antibodies to attack germs. Most vaccine candidates in human trials today use that strategy.

Jay A. Levy, an AIDS researcher at the University of California at San Francisco, said he believes that the cellular approach is the only one that will work. "You aren't going to prevent HIV infection by the classic vaccine model," he said.

But Francis was not dissuaded. He took his data to the NIH and asked for funding to test his vaccine in a large group of humans. He ran into a wall of opposition.

Moore and Dennis R. Burton of the Scripps Research Institute argued in the journal Nature Medicine that funding for vaccine trials is limited, that patient cohorts are precious resources, and that "a social and political price" would be paid for a vaccine that failed in a large-scale trial.