AIDS vaccine test suffers a setback

Monkeys that show resistance to virus appear to fall sick, die

Associated Press

BOSTON -- The death of three monkeys that had gotten an AIDS vaccine in a Boston lab suggests that a closely watched strategy intended to blunt the deadly progression of HIV may not provide total protection from the disease.

For several years, researchers have concentrated on crafting vaccines that prompt the body to mount a vigorous challenge to HIV and hold the virus in check.

Much enthusiasm for this approach comes from experiments on monkeys, which appear to survive for years with these vaccines even after they receive high doses of the monkey form of HIV.

However, at a conference Wednesday, researchers from Beth Israel Deaconess Medical Center in Boston who helped develop the strategy reported that monkeys eventually appear to fall sick and die, even after showing promising resistance to the virus.

"This suggests that viral escape will prove to be a challenge," Dr. Daniel Barouch, one of the Boston researchers, said at the 10th Conference on Retroviruses in Boston.

In his experiment, three of four vaccinated monkeys got sick during three years of follow-up after their shots with an experimental vaccine created by Merck & Co.

Typically these new vaccines take a two-step approach. The first, called the prime, is HIV genes that are injected into muscle, where they are taken up by cells and result in production of viral proteins. The second is the boost, often a harmless hollowed-out virus that carries in more HIV genes.

Together, if all goes as planned, they induce the body to mount an attack by killer T cells that destroy HIV-infected cells. This may not prevent an infection, but it can minimize its consequences by keeping virus levels low.

Dr. David Ho, scientific director of the Aaron Diamond AIDS Research Center in New York City, said the monkey deaths are "enough to be worrisome."

In fact, Ho said the emphasis in the vaccine field seems to be shifting back toward an older strategy that many had dismissed as unworkable against HIV. Ordinarily, vaccines do their job by prompting the immune system to churn out antibodies that recognize an invading germ and kill it before it ever establishes an infection.

Even though the body readily makes antibodies against HIV, they cannot penetrate a thick coat of sugar that covers the virus' surface. However, new studies suggest it is possible to concoct antibodies that actually do kill HIV, and studies are under way to find ways to trigger their production.

Several vaccines based on the prime-boost approach are already in human testing, and the Boston monkey results do not mean they are doomed. The monkeys received only the prime, not the boost, stage of the strategy, and some experts said the experiment is not a fair test of the current generation of vaccines.

Among the furthest along are vaccines from Merck that have been given to about 600 human volunteers so far.

Dr. Norman Letvin, another of the Boston researchers, said scientists assumed from the start that the vaccine would not always stop the virus completely. Unvaccinated monkeys fared even worse, so "this tells us that a T cell vaccine has the ability to slow disease progression."