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Vaccine Shields Monkeys From Simian Form of HIV
Date:5/17/2009

Scientists inject antibody-coding genes directly into muscles

SUNDAY, May 17 -- Raising hopes for the development of an AIDS vaccine that might actually work, researchers report they were able to protect monkeys against infection with simian immunodeficiency virus (SIV), the primate version of HIV.

They did so by using a novel approach that delivered antibody-producing genes directly to the animals' muscles. Typically, vaccines are aimed at ramping up the immune system to fight off infection, but this strategy eliminated that middle step.

"Traditional approaches toward developing an HIV vaccine that have worked for other viruses like influenza have just has not worked for HIV and, quite frankly, might not work for a long time or ever," explained the study's author, Dr. Philip R. Johnson, chief scientific officer at Children's Hospital of Philadelphia and a professor of pediatrics at the University of Pennsylvania School of Medicine.

"But Mother Nature has allowed us a few breaks, in that we know that in a very few cases, people who have been infected for a very long time have been able to naturally develop antibodies that neutralize a lot of the circulating virus," he said. "So, we thought perhaps we could take the genes that represent these antibodies 'off the shelf,' so to speak, give them directly to patients and, in essence, bypass the immune system."

"So, first we worked through mice and showed we could do it with mice," Johnson explained. "And now we've shown that we can actually transfer these genes into monkeys and protect these animals from SIV."

The findings are in the May 17 online issue of Nature Medicine.

The researchers' efforts focused on preventing SIV infection in nine macaque monkeys who were "immunized" against SIV by inserting genes already known to express anti-SIV antibodies directly into the monkeys' muscles.

Once the genes were injected, they prompted the muscles to produce antibodies that were released into the bloodstream and began attacking the SIV.

After being exposed to SIV four weeks later, six of the nine monkeys appeared to be fully protected from infection because they remained completely uninfected, and none of the nine immunized monkeys went on to develop AIDS or died from exposure to the virus, the researchers reported.

In contrast, six non-immunized monkeys exposed to SIV all became infected, and two-thirds died.

Johnson and his team concluded that their immunization strategy triggered the development of long-lasting and complete protection against SIV infection among monkeys.

"I'm not about to over-hype this," Johnson cautioned. "But we are continuing our work with monkeys in parallel with moving forward to begin human trials in two years, if everything goes perfectly with our work with the FDA to develop safety preparations, which is absolutely appropriate. And if the immunization trials work, then you have another few years to gear up. So, in the best of all possible worlds, you're looking at five years down the road for a practical benefit for patients. But, scientifically, we believe we are on the right track."

Rowena Johnston, director of research at the Foundation for AIDS Research in New York City, described the work as "one of the most interesting and potentially promising concepts to come out of the vaccine field in quite a while."

"They've cut straight to the chase and eliminated the middle man," she explained. "That is the really exciting thing they've done. We already all know that the traditional approaches to a vaccine won't work for HIV. And so HIV is a field where researchers are required to come up with ideas that nobody has needed to think about before, and that is where the challenge is. And here what they've done is to get antibodies to the virus themselves being produced directly, rather than waiting for the very slow-moving immune system to respond. And that is so elegant."

"Of course, the caveat is that this paper is a concept, and not yet a solution," Johnston noted. "But as concepts go, this is very, very interesting, even if it seems so obvious after you see it, like all good research."

More information

The World Health Organization has details on efforts to develop an HIV vaccine.



SOURCES: Philip R. Johnson, M.D., chief scientific officer, Children's Hospital of Philadelphia, and professor, pediatrics, University of Pennsylvania School of Medicine, Philadelphia; Rowena Johnston, Ph.D., vice president and director, research, Foundation for AIDS Research, New York City; May 17, 2009, Nature Medicine, online


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