AIDS vaccine: preliminary but promising.

AIDS vaccine: Preliminary but promising

Researchers last week reported a series of significant, incremental steps toward a vaccine to protect against AIDS. They emphasize that general availability of such a vaccine remains, at minimum, many years away. But the recent progress brightens what has been an extremely downbeat assessment of the prospects for an AIDS vaccine.

Speaking in Montreal, Quebec, at the Fifth International Conference on AIDS, Jonas Salk of the Salk Institute for Biological Sciences in San Diego presented early but encouraging results from experiments in chimpanzees and humans infected with the AIDS virus, HIV. Unlike most experimental AIDS vaccines, which use small portions of HIV to trigger a protective immune response, Salk's vaccine contains whole AIDS viruses killed by treatment with chemicals and radiation. Salk used a similar method in the 1950s to make the first commercial vaccine against polio.

While other experimental AIDS vaccines use proteins from HIV's outer envelope to stimulate immunity, Salk's chemical/radiation treatment disintegrates this envelope. Yet the vaccine appears to eliminate HIV from chimpanzees, suggesting it might not only prevent infection but also halt disease progression in already-infected individuals.

Salk and Clarence J. Gibbs of the National Institutes of Health vaccinated two HIV-infected chimps and one uninfected chimp, then followed up with two boosters. Three months later, they infected the three chimps and an unvaccinated control chimp with large "challenge" doses of live HIV. Following that challenge, they detected no HIV in the first two chimps. The originally uninfected, vaccinated chimp tested HIV-positive for a few months after the challenge but has remained HIV-free since then. The unvaccinated chimp's infection has worsened.

In tests assessing safety and side effects rather than effectiveness, the researchers also vaccinated HIV-infected humans showing early signs of AIDS and saw no complications. Moreover, of these 19 patients, seven show increased numbers of immune system cells called CD4s -- an indication of improved immune strength, says study collaborator Alexandra M. Levine of the University of Southern California in Los Angeles. Four show a decline in CD4s. Perhaps significantly, six of the seven with increasing CD4s -- but none of the four with falling CD4s -- show evidence of a specific form of cell-mediated immunity against HIV, as determined by skin tests resembling the commonly performed tuberculin test. Increasingly, researchers believe that an effective AIDS vaccine will have to induce both antibody-mediated immunity and this cell-mediated immunity. Although most vaccine research emphasizes the former, the latter seems more effective at wiping out cells that harbor HIV.

Salk's group and others say that while these results appear encouraging, any real benefits from the vaccine in humans must await larger, controlled trials. Nonetheless, Salk predicts that his vaccine--at least in conjunction with other therapies -- may prevent disease progression in infected adults and in congenitally infected babies. "The diagnosis of HIV seropositivity need not be regarded as a death sentence," he says.

National Cancer Institute researcher and HIV co-discoverer Robert C. Gallo calls the results intriguing but has some reservations about the approach. "When you use a killed whole virus, it's impossible to guarantee there's not a live virus left" in the vaccine, he warns.

Other researchers at the Montreal meeting reported progress toward identifying key antibody-inducing fragments of the HIV envelope. And in the June 1 NATURE, researchers at the University of Reading in England and two other British institutions describe a promising vaccine made from an HIV protein bound to a strain of poliovirus developed by Albert Sabin, the virologist who once raced Salk to develop the first polio vaccine.