Voice of America - May 20, 2009
Jessica Berman
Washington

U.S. researchers have developed an experimental vaccine against the virus that causes AIDS using a novel technique that leapfrogs the body's natural immune system. The new vaccine, successfully tested in monkeys, is still years away from human use. But it offers new hope of preventing the spread of a disease that has already killed 20 million people and infected 33 million more around the world.

Dr. Philip Johnson and a team of researchers at Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine decided to pursue their novel approach because, Johnson says, all previous efforts to get the body's natural immune system to fight off an HIV infection have failed.

"I think that the time has passed and people have seen that the traditional methodologies, the traditional approaches, have not worked. And there's no evidence that they will work in the short term," Dr. Johnson said.

Instead, Johnson and his colleagues pursued a strategy they've been working on for 10 years that focuses on special antibody-like proteins that can neutralize the HIV virus. Bypassing the immune system, the investigators created the proteins from a variant of HIV called SIV, which infects monkeys. They engineered the DNA of these proteins into a harmless cold virus and injected this modified carrier into the muscles of laboratory monkeys that were not infected with SIV.

Once injected into the muscles, the transferred genes began producing and pumping out anti-SIV proteins - called immunoadhesins - that circulated throughout the monkeys' bloodstream, binding to SIV and preventing the virus from infecting healthy cells.

In order to produce a vaccine for humans, Johnson says researchers would make immunoadhesins from people who have been infected with HIV for decades, in some cases before they developed AIDS.

"And what we can do is go into those individuals, take cells from them and then actually tease out the genes that are responsible (for keeping AIDS at bay). And then we can use those genes to develop new molecules in the lab that we can turn around and give back to people who have never been exposed to HIV. And in the case of the monkey study that we just published on, we were able to protect the monkeys using that approach," Dr. Johnson said.

The study, published in the journal Nature Medicine, involved nine rhesus macaques that were injected with the modified SIV immunoadhesins.

When they were injected with live SIV four weeks later, six of the monkeys were completely protected from infection. And researchers found that more than a year later, all of the monkeys still had high concentrations of the antibodies in their blood.

By contrast, a group of six unimmunized monkeys became infected with SIV, and four of them died during the experiment from AIDS complications. The three immunized monkeys infected with SIV never developed AIDS.

Seth Berkley, president and founder of the International AIDS Vaccine Initiative, says the SIV vaccine represents an important milestone.

"We're not sure this is ultimately going to be a vaccine. But if we can take this approach and show protection, that gives you a proof of concept and nothing would be more important to the field to have than a proof of concept, and also being able to set the levels of antibody required and understand the protection," Berkley said.

Meanwhile, Dr. Philip Johnson and his colleagues plan to meet soon with U.S. Food and Drug Administration regulators to work out the details of human vaccine trials, which could begin within the next two years.

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