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The quest for an HIV vaccine has been given a bad prognosis recently, due to increasing agreement that the human immune system isn’t clever enough to outsmart the ever-changing surface of the virus. But now a new approach promises to solve the problem by sidestepping the immune system altogether, instead using gene therapy to produce immune molecules that neutralize the virus.

Reporting in Nature Medicine this week, Philip Johnson, a professor of pediatrics at the University of Pennsylvania, in Philadelphia, and his colleagues managed to protect monkeys from infection with the simian immunodeficiency virus (SIV), the animal model that is closest to HIV, by shuttling a gene into their muscles that produces antibody-like molecules that work against SIV.

With both SIV and HIV, the chameleon-like mutability of the virus changes its surface so quickly that most antibodies made by the immune system are soon rendered ineffective, explains Johnson. “I concluded about 10 years ago that traditional approaches weren’t going to work,” he says. “Successful vaccines all mimic the body’s natural immune response and this just does not work well in HIV-infected people. HIV is too good at hiding itself from the immune system.”

Some antibodies have been shown to neutralize SIV, although exactly how they do this is not well understood. Getting the human immune system produce the few known antibodies that show similar potential for neutralizing HIV has also been impossible.

To tackle this problem, Johnson turned to another virus for help. A modified version of the adeno-associated virus (AAV) has been proved to work as a convenient vector for delivering gene snippets safely into the human body for gene therapy, and it has been used successfully to treat hemophilia and congenital blindness by supplying patients with genes that are otherwise missing.

Johnson and his colleagues designed DNA sequences for particularly stable versions of two antibodies known to be effective against SIV. They used antibody-like molecules, called immunoadhesins, in which the functional part of an antibody is fused with a more stable section of another antibody.

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Tagged: Biomedicine, virus, vaccine, HIV, immunotherapy, antibody

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