United Press International, October 19, 2000, Thursday AIDS vaccine fends off virus in monkeys A vaccine that hypercharges the production of "killer" T immune cells has at least temporarily thwarted the development of AIDS in rhesus monkeys as well as damped the virus's ability to copy itself. The Boston-based study, which will appear in Friday's issue of Science, marks the first time a DNA-based vaccine has protected against the disease's progression in monkeys. "What they've done here, 10 or 20 years ago would have been seen as science fiction," said Dr. Keith Henry, director of the HIV Program at Regions Hospital in St. Paul, Minn. and director of the AIDS Research Consortium, Twin Cities, after reviewing the paper. "The message is: the immune system, if given some help, can be taught to do a pretty good job," Henry told United Press International. "That's ultimately where a lot of people see the field going" -- trying to develop a vaccine not to block the ever-changing virus completely, but instead to equip the body's immune system to keep an infection in check. Researchers from Harvard University Medical School, working at Harvard's Beth Deaconess Medical Center, designed their double-pronged vaccine as a twist on the DNA vaccine, an AIDS vaccine now undergoing wide testing. To boost the action of the DNA vaccine, they added a special protein. The fusion protein combined interleukin-2, a chemical messenger that cranks up T cell activity, and immunoglobin, which keeps interleukin in the system longer. In February 1999, the team at Beth Israel began a series of three vaccinations and a booster shot over a 10-month period. In January, the researchers injected the eight vaccinated monkeys, as well as a control group of eight monkeys, with a high dose of a highly virulent cousin of HIV. After about four and one-half months -- 140 days -- none of the vaccinated monkeys showed symptoms of AIDS, and the amount of virus in their blood was low or undetectable. Meanwhile, the vaccinated monkeys' level of "killer" immune cells (CD8 cytotoxic T lymphocytes) had risen to five times their pre-vaccination levels. These killer immune cells can attack cells infected with the AIDS virus -- in both monkeys and people -- and stymie the virus's ability to replicate. The fate of the control group was entirely different. The monkeys showed persistently high amounts of virus, a decline in immune cell counts and clear signs of the disease. Four died. "Do I think this may translate into a human setting? I think it may," said the paper's senior author, Dr. Norman Letvin, a long-time AIDS researcher. "But the type of vaccine needed to generate this killer T cell response may be different; and how profound an effect that such an vaccine-induced immune response might have on clinical disease remains to be seen." Taking this type of vaccine into human trials, he said, is the only way to see how dramatic or subtle the progression of AIDS might be in people. Letvin said nothing in the study suggests that the vaccine would work as a therapy following HIV infection; that would require further research. Vaccines produce immunity to a disease by triggering the formation of antibodies. However, the virus causing AIDS mutates so frequently that this approach has not appeared workable. The Harvard researchers who developed the boosted DNA vaccine did not expect it to prevent the monkeys from acquiring the virus, but instead to help them kill infected cells. If such a vaccine worked similarly in humans -- a big if, cautioned the study's lead author, Dr. Dan Barouch, a researcher and clinical medicine resident at Harvard Medical School -- the lowered viral counts could help stem the spread of the epidemic. Many clinical human studies have shown that an individual's viral load predicts two things, he said: How quickly the disease will progress and their odds of transmitting the virus. "Unfortunately, we have no time frame," Barouch said, for when such work might be ready for human trials. Critical questions remain: Will the monkeys be healthy a year from now? Will the results translate to humans? Will the shot still offer protection if the vaccination is given long before exposure to the AIDS virus, as may happen in the real world? Even if the answers are disappointing -- and scientists involved in AIDS research have faced disappointments before -- the research is significant, said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. and distinguished HIV researcher. "It validates the concept of a DNA vaccine." The National Institutes of Health funded the research as part of the $265 million to $270 million it devotes each year for research on AIDS vaccine development and clinical trials. The DNA-plus-protein vaccine built on previous research at the Harvard lab and elsewhere. DNA vaccines do induce an immune response, Fauci said. But the response is neither potent enough nor durable enough to increase T cells the way that this souped-up DNA vaccine did. The DNA vaccine "needed another whallop to it," Fauci said. "That's why the booster is an important part of the proof of concept." While the vaccine did not prevent the monkeys from acquiring the virus, it may set the direction for the most-promising approach for a vaccine: One that controls HIV and transforms it into a mild condition, said Fauci and St. Paul's Henry -- provided such vaccines can contain the virus for a decade or more. "I'm not so sure we're going to have a vaccine that is going to be able to protect completely against infection in a large number of people," said Fauci. "A vaccine that has the effect of protecting against the progression of the disease would, in my mind, be a major step." Henry sees promise in the approach for preventing other diseases and infections, such as hepatitis C. He hopes the study will spur researchers and industry to delve more deeply into the mysteries of the immune system, seeking imaginative solutions to both HIV prevention and treatment. "Right now, despite a lot of talk, almost nobody is getting treatment," Henry pointed out. "Ninety percent of the world that needs therapy is not on treatment. Everybody is throwing up obstacles: 'It's too expensive, it's too complicated.' It's nice to have a gee-whiz story that provides some sort of inspiration."
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