The Elusive Search for an AIDS Vaccine

Scientists hope for at least some success by decade's end

MONDAY, Dec. 1, 2003 (HealthDayNews) -- After a disappointing year of research findings, scientists are little closer to developing the Holy Grail of AIDS prevention -- a successful vaccine.

But researchers, doctors and activists still hope to find success by the end of the decade.

At stake is a way to stop the transmission of AIDS without relying on humans to reduce their tendencies toward risky sexual behavior. If scientists are successful, the disease could head toward decline.

"All of us are cautiously optimistic," says Wayne Koff, senior vice president of research and development at the International AIDS Vaccine Initiative, an advocacy organization.

Those words of tempered hope come as nations pause Dec. 1 to note World AIDS Day. The epidemic, which began more than two decades ago, has killed an estimated 23 million to 25 million people worldwide so far.

Researchers earlier this year reached the end of the most extensive vaccine study to date -- the so-called AIDSVAX vaccine that was administered to people in the United States.

To the astonishment of experts, the vaccine failed to protect against AIDS infection among whites and Latinos, but worked quite well for blacks and Asians. Many critics quickly discounted the study, saying it was too small because only a few hundred non-whites were included among the 5,400 subjects. Others wondered if some genetic difference between the races could account for the discrepancy.

In November, researchers released the results of another study that examined a variation on the AIDSVAX vaccine geared toward AIDS strains that are common in Asia. The vaccine, given to half of a group of 2,546 intravenous drug users in Thailand, failed to do any better than a placebo given to the other half.

Vaccines, of course, are available to combat a variety of diseases, from mumps and measles to smallpox and polio. Even chicken pox, the usually mild but sometimes disfiguring perennial disease of childhood, has given up the ghost to a vaccine.

Considering the record of vaccine success, why is AIDS such a challenge?

"There are two hurdles," says Dr. Steve Black, director of the Kaiser Permanente Vaccine Study Center in Oakland, Calif. "One is that the virus itself is attacking the immune system. It's attacking your body's main defense against the disease. Even if you have a vaccine that generates an appropriate immune response, there's no way to make sure the infection itself won't undermine that."

The other challenge lies in the ability of HIV -- the AIDS virus -- to morph into different forms. Other diseases simply don't do that, Black says. "Measles is measles, pretty much. If you vaccinate people, they're protected."

AIDS, on the other hand, is more like the influenza virus, which changes so often that pharmaceutical companies must tinker with the formulation of flu vaccines each year. "HIV does that at even a faster clip," Black says.

One possible solution for the first part of the challenge would be to use what's called a live attenuated vaccine -- a harmless, weakened form of the AIDS virus that would force the immune system to permanently create antibodies, the microscopic soldiers permanently on guard against a specific germ.

The polio vaccine, among others, works in that way. "When the body sees the polio virus, it can attack and neutralize it, you don't get the disease," Koff says.

But there's a problem. "In HIV, you can elicit a lot of antibodies and they can bind to HIV, but most of them are not effective in neutralizing HIV in the right way," Koff says.

Koff and other experts suspect that the most feasible approach may be to design a "combination" vaccine that both primes the immune system and arms cells themselves against the bits of virus that make it past the first wall of defense. The second part of the vaccine would "stimulate the immune system to produce cells that are capable of killing the virally infected cells," Koff says. "It's not the first line of defense. It's the next line of defense."

For now, a useable vaccine appears to be years off. While about 20 vaccines are in or near the stage of studies in humans, only the AIDSVAX vaccines and one more vaccine have reached the final phases of research, Koff says. Results of the study of the latter vaccine, derived from a canary virus, are pending.

"It's conceivable to have a partially effective vaccine by the end of the decade," Koff says. "It can have significant benefit on the public health. Remember that 15,000 people a day are becoming infected with HIV. Even if you have a vaccine that's 40 to 50 percent effective, you can make a significant amount of impact."

More information

Learn more about HIV vaccine development from the HIV Vaccine Trials Network and the International AIDS Vaccine Initiative.

SOURCES: Wayne Koff, Ph.D., senior vice president, research and development, International AIDS Vaccine Initiative, New York City; Steve Black, M.D., director, Kaiser Permanente Vaccine Study Center, Oakland, Calif.
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