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EMPTY SYRINGES: After 20 years of searching, the world is still without a vaccine to battle HIV.
© ISTOCKPHOTO/MAXIM PIMENOV

On July 17, a high-ranking official at the U.S. National Institutes of Health (NIH) pulled the plug on a hotly anticipated clinical trial for a government-funded vaccine to combat human immunodeficiency virus (HIV), the bug that causes full-blown AIDS. The announcement by Anthony Fauci, director of the NIH's National Institute of Allergy and Infectious Diseases (NIAID), was the latest in a series of setbacks in the search for a vaccine the world has been anxiously awaiting for more than two decades.

Fauci's reason for canceling the trial: There is not enough evidence that it's effective to justify a wide-reaching trial.

Vaccines come in two forms: protective and therapeutic. A protective vaccine typically consists of a weakened form of a virus that, when injected, alerts the immune system (antigens or proteins on the virus' surface), which in turn generates antibodies (other proteins) that clobber the invaders and remain on high alert should the bug ever try to attack again. If the virus hits again, the immune system will be armed and ready, with the weapons it needs to launch a preemptive strike to wipe it out before it can infect any cells.

Therapeutic vaccines are designed to battle illnesses already in the body by helping disease-killing T cells recognize and target them. In the case of HIV, candidate vaccines typically consist of parts of the virus that furtively slipped into the body and is successfully eluding the immune system. Whereas the virus entered the body undetected, the protein does not: The T cells will view it as a dangerous invader and attack it everyplace in the body, including on the viruses, reducing and perhaps even clearing the infection completely.

Fauci said that he nixed the trial, in part, because of the failure of Merck & Company's 3,000-person STEP vaccine trials in September. In lab tests, the Merck vaccine showed that immune system cells produced signaling proteins called cytokines when they came in contact with the vaccine. Researchers believed these so-called "correlates of immunity"—essentially signs that immune system was responding to the vaccine— indicated that it would fight infection.

They were wrong: The Merck vaccine proved ineffective at preventing infection or reducing levels of the virus in an infected person's body. The government-funded vaccine, known as PAVE (Partnership for AIDS Vaccine Evaluation), is formulated similarly to Merck's vaccine, consisting of three genes found in HIV attached to a weakened form of the common cold designed to draw the attention of the immune system. Originally set to be tested on 8,500 people, PAVE's trial was downsized to 2,400 soon after the failure of the Merck vaccine.

After a NIAID-sponsored summit in March revealed that there were too many unanswered questions, Fauci decided that priorities needed to be revised.

Toward that end, has co-authored an article in Science last week that calls for more basic research and smaller studies (to prove a candidate vaccine's effectiveness) before conducting large-scale human trials. Fauci spoke with ScientificAmerican.com to discuss this new tack—and whether there's still a chance of an HIV vaccine.