Some wonder whether it might be valuable to launch a large human trial of a marginal experimental vaccine, hoping that a few individuals would develop immunity so they could be studied.
"Do we really want to blow $30 million on a candidate vaccine that we're not sure will work to get more information about correlates of immunity?" Sheppard asked. "Some believe it's not worth it. Others believe it's absolutely critical to get to the next level of protection. That's where some of the tension is."
Unfortunately, only limited information can be obtained from animal studies. There is no ideal animal model for studying HIV vaccines. Chimpanzees can become infected with HIV, but only one chimpanzee is known to have become ill. Moreover, chimpanzees are an endangered species.
So most HIV animal studies use macaque monkeys. They can be infected with simian immunodeficiency virus, which is similar to HIV and causes an AIDS-like disease. But results cannot always confidently be applied to humans.
During last week's forum, Dr. Opendra Narayan of the University of Kansas Medical Center in Kansas City reported that he had developed a live-virus candidate vaccine that appeared to protect a small number of macaques from exposure to a lethal, lab-created hybrid virus that contained an HIV component.
Fears of Mutating Virus
The virus, dubbed SHIV, was made by combining SIV with a piece of HIV taken from its envelope, or outer coat.
Researchers would be delighted to end up with a live-virus vaccine but have shied away from that approach because of serious concerns about safety.
Historically, the best vaccines are often made from live, attenuated viruses. These are living viruses that have been altered to make them harmless, or capable of causing only mild disease.
But AIDS researchers worry that a live-virus vaccine, even crippled in some way, might find a way to repair itself once in the body or, even worse, meld with another HIV strain to form a more dangerous "mosaic" virus.
HIV is a retrovirus--its genetic material is RNA rather than the usual DNA. Upon infecting a cell, it undergoes a special process to turn its RNA into DNA, integrating with the DNA of the host (human) cell.
"We don't know how the body would handle" an attenuated vaccine, said Dr. Larry Arthur of the National Cancer Institute. "Theoretically, once you're infected with a retrovirus, you're infected for life."
"I've always been a strong proponent of attenuated vaccines," he added. "There are certainly enough areas of the world with high-risk people that would warrant testing one. But there is a big potential safety risk."
Arthur has been developing DNA-based vaccines, which use pure--but noninfectious--genetic material from HIV.
Other strategies under study include using a live but harmless "vector," such as a bacterium or another virus, to "carry" an HIV protein gene; using chemically synthesized pieces of HIV proteins, known as peptides, and using a noninfectious HIV look-alike.
No one has yet put a live HIV vaccine in humans, although some experts point to a fascinating case in Australia as evidence that such a trial might not prove as dangerous as many people think.
More than a decade ago, a handful of individuals received transfused blood from an Australian infected with a genetically impaired strain of HIV. One recipient died, but it was unclear whether AIDS was the cause.
None of the others has developed AIDS, raising the possibility that giving individuals a live vaccine using HIV with this same genetic defect might, at least, be safe.
But would it result in immunity?
"Some say: 'Look at these people, they don't get sick. Given the apparent failure of other approaches, do the trial,' " Sheppard said. "But others say: 'No. Safety issues are paramount. We just can't do it.'
"And who knows who is right?"
