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Fake virus could make safe new vaccines

Posted: Saturday, June 28, 2008, 20:39 (BST)
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A "wimpy" artificial virus protected mice against polio, and the approach might be used to make a range of safer new vaccines against viruses, U.S. researchers reported on Friday.

The team at the State University of New York, Stony Brook, had created the first artificial virus, a synthetic version of polio, in 2002.

Reporting in the journal Science, they said they used it to vaccinate mice, and then infected the mice with what should have been a deadly dose of polio. The mice survived.

"Ultimately we created a wimpy poliovirus that can be customized and does not cause disease unless given at high doses," Bruce Futcher, a professor of molecular genetics and microbiology who worked on the study.

"These viruses are still far from suitable vaccines for humans, but there is a lot of potential for this approach," he added in a statement.

The researchers used a unique method to make their virus, relying on a built-in redundancy in DNA, the material that carries genetic instructions in organisms.

DNA's code is written using just four nucleic acids, represented by the letters A, C, T and G. These are combined in various ways to make amino acids, which in turn make proteins.

It is possible to make an amino acid with more than one combination of these letters - for example, GCC and GCG both code for the amino acid alanine. For unknown reasons, organisms favor certain combinations.

SAFER VACCINES?

Futcher's team made their polio virus using the less-favored combinations of the virus's genetic code.

They hoped these would stimulate the immune system in the same way as "wild-type" polio, without causing disease, and that is what appears to have happened, they wrote.

Each difference in the genetic code weakened the virus in a different way.

"This 'death by a thousand cuts' strategy could be generally applicable to attenuating many kinds of viruses," they wrote.

"Even for an inactivated rather than live virus approach, these features would allow a vaccine to be made from a safer starting material than the corresponding wild-type virus."

Polio vaccines have virtually eradicated the disease in most countries. But an oral vaccine that uses a weakened version of a live polio virus can sometimes get back into the water supply and mutate into a form that can infect people.

Doctors have been looking for a safer yet effective polio vaccine that is as easy to administer as the drops. Dr. Jonas Salk's original polio vaccine, which effectively rid the United States of the feared virus in the 1950s and 1960s, used a "killed" polio virus but had to be injected.

The letter-by-letter changes needed the help of a powerful computer, said computer science professor Steven Skiena, who worked on the project.

"Sophisticated computer algorithms are necessary to design the hundreds of changes to sufficiently cripple the virus for our 'death by a thousand cuts' approach," Skiena said in a statement.

"Because of the large number of changes, the weakened virus can never mutate back to wild-type."



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