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Finding the way again after failed AIDS vaccine

Twenty-one  years after an AIDS vaccine was expected, the world seems farther from an effective shot than ever. So what should be done next?
/ Source: NBC News

"We hope to have a vaccine ready for testing in about two years," Margaret Heckler, the secretary of Health and Human Services, said during a 1984 news conference announcing the discovery of the virus the causes AIDS. "Yet another terrible disease is about to yield to patience, persistence and outright genius."

But 23 years later, after billions in research expenditures, the world seems farther from an effective AIDS vaccine than ever.

Indeed the vaccine development world is now in a state of stunned shock since the trial that many believed had the greatest chance of success was halted. At this point, it looks like an AIDS vaccine remains decades away, if one is ever to be found

Merck’s experimental vaccine did not simply fail to protect people. There were more infections among men who got the vaccine — 49 out of 914 — than those receiving a placebo — 33 of 922. There is no way the vaccine itself could have infected people. But the results raise the frightening prospect that the vaccine actually increased people’s chance of getting infected through sex or injection drugs.

“I don’t want to be Pollyanna and I don’t want to be Chicken Little. But we could have a very serious problem,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Fauci’s institute put up $20 million for the trial called STEP that recruited 3000 volunteers in the United States, Canada, Australia, South America and the Caribbean. Merck will not say what it spent to develop the vaccine but outside experts say tens of millions would be a conservative estimate. More important, Fauci’s institute was about to embark on a separate trial costing $130 million that used two kinds of vaccines, including one very similar to the vaccine used in STEP. That trial called PAVE 100 was set to begin in January put has now been postponed indefinitely. On December 12, a panel of experts will meet at the National Institutes of Health to try to begin to chart the course forward.

Looking back to find the way forward
The biggest challenge is to try to understand what happened with STEP. One of the simplest answers is to the question of why there was no effect in women who made up half the volunteers. The trial recruited mostly female sex workers. And prostitutes have become very good at avoiding infection with HIV by demanding their customers wear condoms. Indeed there was only one infection in a woman in the entire trial and she was getting the placebo. The lesson for future trials is to recruit women whose boyfriends or husbands may be putting them at risk.

But what happened among the mostly gay male volunteers? Merck’s vaccine combined three proteins produced by the AIDS virus with a modified form of a virus that causes the common cold (adenovirus 5).

Preliminary analysis of the data finds that those who became infected with HIV mounted the strongest immune reaction to the adenovirus. This could be a fluke with this adenovirus. But it also could be something far more significant.

Chilling possibility
For many years a basic tenet of AIDS research is that any vaccine needs to increase the production of T cells – the part of the immune system that finds and destroys infected cells. But perhaps an increased T cell response just makes infection more possible. If that is true, all vaccines that are now being tested could be like trying to treat gunshot wounds by firing a pistol at the patient.

“That is entirely conceivable,” Fauci said, “and I don’t think you can, by wishful thinking, rule that out.”

Vaccines based on other concepts are still in the laboratory and testing in humans, according to Fauci, is “years and years away.”

So what should be done next? Clearly many scientists must carry out as many experiments as possible to understand the STEP results. Dr. Seth Berkley, head of the International AIDS Vaccine Initiative, emphasizes the race to find a vaccine is a “marathon not a sprint” and we should not lose sight of the goal.

But meanwhile we do know that treatment works well for those who are infected, and old-fashioned prevention efforts keep people from getting infected in the first place. Perhaps it is time to re-think the priorities.