Spotlight: AIDS Vaccine

After a two-decade drought of good news, AIDS-vaccine researchers are finally dancing under the first raindrops of hope. It's not a downpour by any means or even a soaking shower, but it's something. At the end of a six-year vaccine field trial--the largest ever conducted--scientists have their first successful immunization against HIV.

But success, especially in science, is relative. Yes, as media reports immediately crowed, the vaccine was 31% effective at reducing the risk of HIV infection among the 16,000 healthy volunteers in the study. But that's nowhere near the 70%-to-80% rate that most public-health experts say is the minimum needed for an immunization to be judged worthwhile. Consider also that circumcision can cut the risk of HIV infection nearly twice as effectively, up to 60%.

The raw data from the trial, conducted in Thailand, will be presented at an AIDS-vaccine meeting in Paris on Oct. 20. Until then, researchers have only some intriguing and, frankly, puzzling snippets of information--and plenty of questions. The trial actually tested two vaccines: one that primes the immune system by training cells to recognize and destroy the virus and one that boosts that response. Neither shot has proved effective alone, yet together they seemed to trigger a modest immunity--although no one yet knows why. Fifty-one people who received the vaccine became infected with HIV, compared with 74 who received a saltwater placebo, a barely significant difference. And while a lower risk of infection normally derives from a drop in the amount of virus circulating in the blood--with less virus floating around, there is less chance that HIV can bind to healthy cells--that did not happen in this study. Which means that although those who are vaccinated might be protected, they are still very infectious and can continue to spread HIV--not an ideal side effect of a vaccine meant to contain an infectious disease.

"Do we have a vaccine we would use to prevent HIV? No," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), which picked up the bulk of the $105 million cost of the study. "But if it gives us enough information that would be helpful in the next steps toward development of a vaccine, then it's a successful trial."

The Thai study is already a winner in that researchers now have a population of patients who are protected against infection with HIV after inoculation; they can begin to analyze the patients' immune responses more closely to tease out the elusive factors that shielded them from HIV. That's more than the last promising vaccine provided. That candidate, made by Merck, not only failed to protect volunteers from infection but also seemed to increase their risk of contracting HIV.

Remarkably, the current groundbreaking trial almost never saw the light of day. NIAID inherited it from the Department of Defense in 2003, by which time 1,000 volunteers had already been enrolled. Fauci says he was loath to pull the rug out, despite having rejected a trial for a similar pair of prime-and-boost vaccines that came through the institute around the same time. "I was hoping when I made the decision to allow this trial to go ahead that we would at least learn something from it," says Fauci. "Guess what? We are." Maybe more than anyone could have anticipated.