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Study Points to Possible Route for AIDS Vaccine
Maggie Fox, Health and Science Correspondent
October 19, 2000
WASHINGTON (Reuters) - An AIDS vaccine that helped keep monkeys from getting sick could show scientists how to start fighting the HIV epidemic in people, researchers said on Thursday.

The vaccine did not prevent infection, but it did stop monkeys from developing symptoms of HIV infection -- and it kept the animals alive, the team at Massachusetts General Hospital and Harvard University said.

Dr. Norman Letvin, the AIDS researcher who led the study, said it showed that vaccine researchers can lower their sights a bit, seeking not to prevent HIV infection entirely but to use a vaccine to keep people from becoming so ill when they do become infected.

"This study raises the possibility that, while we don't have any approaches in hand that are likely to truly prevent infection, we may have a number of approaches in hand that can generate a killer T-cell response that can alter the course of infection," Letvin said in a telephone interview.

AIDS researchers realize the only answer to the epidemic of HIV, which infects 35 million people worldwide, is a vaccine. But efforts to develop a preventive vaccine have been slow and failure after failure have convinced experts that they need to try for something a little less ambitious.

Letvin and colleagues have been working on a shot that might not prevent infection but might stop people from becoming ill, perhaps keeping them healthy without having to take expensive drug cocktails that have extensive side-effects.

"Since most populations infected with HIV cannot afford drug therapy, this would be of tremendous benefit," he said. He also said the vaccine might make it less likely that an infected person would pass the infection to someone else.

Writing in the journal Science, Letvin and colleagues said they had devised a vaccine that used envelope proteins -- coming from the outside of the virus -- from both SIV, the monkey version of HIV, and human HIV.

This DNA vaccine was boosted with interleukin 2 (IL-2), an immune system protein, and an antibody called IgG.

Working with a team at Merck Research Labs in West Point, Pennsylvania, they tested 20 monkeys by giving them either a fake or real vaccine and then infecting them with SHIV, an engineered human-monkey virus that produces an especially quick and deadly AIDS-like illness in monkeys.

Unvaccinated Monkeys Died Quickly

The monkeys who received the sham vaccine all became sick and half died within 140 days.

"Monkeys that received the experimental vaccine, and there are eight of those monkeys, became infected and early after infection the virus replicated to very high levels. But ... the vaccinated animals appear to be quite good at controlling the level of viral replication," Letvin said.

Importantly, the vaccinated monkeys produced CD8 killer T-cells, also known as cytotoxic T-lymphocytes or CTLs, that attacked the virus.

Letvin said the study showed that producing this strong CTL response is vital to create a working HIV vaccine.

"It is very, very important to remember that this was an experiment done in monkeys, not in humans, and it was an experiment done with a monkey virus," Letvin stressed.

Most vaccines produce antibodies that attach to viruses or bacteria and help other immune cells find and kill them. This does not work with HIV, perhaps because it mutates so quickly.

"The CTL response appears to be very important in controlling AIDS virus infection," Letvin said. "CTL works by recognizing cells that are infected with the AIDS virus and killing those cells."

Letvin said any number of different vaccine formulations might produce a CTL response and he hoped other researchers would now be spurred to develop a formula to test in humans.

Dr. Robert Siliciano of Johns Hopkins University in Baltimore, another HIV expert, called the study exciting.

"It changes the way people will look at what we are able to achieve in the near-term in AIDS vaccines," he said in a telephone interview.

But Siliciano and other experts said the study suggested that vaccines now being tested in people will not do the trick. "Frankly, the current vaccines that have been tested already in humans don't elicit quite as strong a response as seen in these vaccines. So we have got to do better," he said.

Dr. Seth Berkley, president of the International AIDS Vaccine Initiative (IAVI), said he was also encouraged. "Their findings, combined with data on other vaccine approaches and basic research studies, provide more evidence that a preventive AIDS vaccine is possible," he said in a statement.



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