Experiment Shows AIDS Vaccine Unlikely to Give Total Protection From Disease

The death of three monkeys who had received an AIDS vaccine suggests that a strategy intended to blunt the progress of HIV may not provide total protection. Researchers have concentrated on crafting vaccines that prompt the body to hold HIV in check. Monkeys inoculated with these vaccines have survived for years even after receiving high doses of the monkey form of HIV.

But yesterday at the 10th Conference on Retroviruses and Opportunistic Infections, researchers from Beth Israel Deaconess Medical Center, who helped develop the strategy, reported that some monkeys eventually sickened and died, even after showing promising resistance to HIV. Three of four monkeys got sick during three years of follow-up after receiving the experimental Merck & Co. vaccine.

The two-stage vaccines involve a prime, in which HIV genes are injected into muscle and result in production of viral proteins, and a boost, often a harmless hollowed-out virus with more HIV genes. The aim is to induce the body to mount an attack by killer T-cells that destroy HIV-infected cells. While this may not prevent infection, it can minimize consequences by keeping viral levels low.

Aaron Diamond AIDS Research Center Scientific Director Dr. David Ho called the monkey deaths "enough to be worrisome" and said the vaccine field seems to be shifting back to an older strategy that many had dismissed as unworkable against HIV. Ordinarily, vaccines work by prompting the immune system to produce antibodies that recognize and kill invading germs before infection is established. Although the body readily makes HIV antibodies, they cannot penetrate the thick coat of sugar on HIV's surface. But new studies suggest it is possible to concoct antibodies that actually do kill HIV, and studies are underway to find new ways to trigger their production.

Several prime-boost vaccines are already in human testing, and the monkey results do not mean they are doomed. The monkeys received only the prime, not the boost, and some experts said the experiment is not a fair test of the current vaccine generation. Dr. Emilio Emini, head of Merck's AIDS vaccine program, said effective vaccines using the strategy will almost certainly be more sophisticated than the one used on the monkeys, since they will carry more viral genes, giving the body more targets to mount a defense. Dr. Norman Letvin, one of the Boston researchers, pointed out that the unvaccinated monkeys fared even worse, so "this tells us that a T-cell vaccine has the ability to slow disease progression."

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