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Like a general whose direct attacks on the enemy are not working, scientists are now trying to outflank the HIV/AIDS virus. Having failed to develop vaccines that enable the body's natural immune system to battle the virus, researchers are widening tests on inserting a gene into the muscle that can cause it to produce protective antibodies instead. The new method worked in mice and has now proved successful in monkeys, too, they reported this week in the online edition of the journal Nature Medicine. That doesn't mean an AIDS vaccine for people is in the wings, stresses team leader Dr Philip R. Johnson of the Children's Hospital of Philadelphia. Years of work may lie ahead before a product is ready for human use. Nevertheless, Dr Beatrice Hahn, an AIDS researcher at the University of Alabama, welcomes the report. "It basically shows there is light at the end of the tunnel," she says. "It shows thinking outside the box is a good idea and can yield results - maybe we need more of these unconventional approaches." The International AIDS Vaccine Initiative says AIDS is one of the most devastating pandemics. More than 20 million people have died so far and 33 million are living with HIV. Most efforts at preventing the progression of HIV to AIDS have sought to stimulate the body's immune system to produce antibodies. This model has worked for diseases such as measles and smallpox but has so far failed to produce a protective reaction to HIV. So Johnson decided to try something different. "We used a leapfrog strategy, bypassing the natural immune system response that was the target of all previous HIV and SIV vaccine candidates," he says. HIV, or human immunodeficiency virus, causes AIDS and the closely related simian virus, or SIV, affects monkeys.
"Some years ago I came to the conclusion that HIV was different from other viruses for which we were trying to develop vaccines and we might never be able to use traditional approaches," Johnson says. Researchers knew of proteins that could neutralize the HIV virus and so began thinking about whether they could use them to fight the disease. In a decade-long effort, Johnson and a team at Nationwide Children's Hospital in Columbus, Ohio, developed antibody-like proteins designed to attach to SIV and block it from infecting cells. Then they needed a way to get the proteins into the cells. The researchers selected the widely used adeno-associated virus as the carrier because it is an effective way to insert DNA into the cells of monkeys and humans. The virus was injected into muscles, which then began protecting the animals. Scientists first tested the idea in mice and then turned to monkeys because SIV is closely related to HIV and would be a good test model. A month after administering the AAV, the nine treated monkeys were injected with SIV, as were six not treated in advance. None of the immunized monkeys developed AIDS. Only three showed any indication of SIV infection and even a year later they had high concentrations of the protective antibodies in the blood. All six unimmunized monkeys became infected; four died during the experiment. The next step is moving toward human trials, Johnson says. He says he is working with the International AIDS Vaccine Initiative in hopes of getting tests in humans under way in the next few years. 2009-05-21
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