A Successful Failure

By MICHAEL D. LEMONICK

Scientists have been struggling to create an AIDS vaccine since the mid-1980s, so you would think the failure of the most advanced trial of such an inoculation would leave them seriously depressed. But that wasn't the reaction last week when researchers from VaxGen, a California company, announced that its HIV vaccine was largely ineffective.

They were not exactly celebrating, of course. But according to Harvard AIDS researcher Max Essex, nobody really expected it to work. Indeed, says Essex, although a dozen other vaccines are in early stages of testing, "it's extremely unlikely that anything already in trials is going to be a home run." That's because it can take five to 10 years to get a vaccine into clinical trials, and scientists' understanding of HIV has evolved considerably since these vaccines were designed.

VaxGen's AIDSVAX vaccine, for example, targets gp120, a protein on the surface of HIV that latches onto receptors on human immune cells. The virus can then break in, multiply and kill the cell. AIDSVAX has a synthetic version of gp120 that tricks the body into producing antibodies; when real HIV shows up, they're meant to bind to the protein and prevent attachment. But researchers now realize that gp120 can take many forms, and antibodies to one will not work on another. Researchers think that effective vaccines will need to combine gp120 with other approaches.

Thus it was no surprise that AIDSVAX did not prevent infection overall among 5,108 high-risk men and 309 high-risk women. What was surprising was that it seemed to offer some protection--how much is in dispute--for a subgroup of 498 black and Asian subjects. That does not mean there's new hope for Africa, where the AIDS epidemic is worst; this vaccine doesn't target the strain most common there. But scientists know genetics affects immune response. That may have played a role in this trial and will be explicitly tested in newer trials.

Researchers have also learned that human AIDS, unlike diseases such as rabies or smallpox, can't be reliably imitated in animals, so vaccines have to be tested in humans by trial and error. In that sense, the AIDSVAX test was a success even as it failed. "For so many years," says VaxGen's president, Dr. Don Francis, "the conventional view was that we couldn't do efficacy trials for AIDS vaccines. You couldn't get volunteers, and people would increase their risk behaviors if they thought they were protected. We've proved that you can do trials with the highest of standards and get them to yield good answers, and that's very important." --By Michael D. Lemonick. Reported by David Bjerklie/New York

With reporting by David Bjerklie/New York