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Published: 10/6/2005

Study confirms flu vaccine just shot in the dark

BY JENNI LAIDMAN
BLADE SCIENCE WRITER

Influenza season is not on its way. Instead, look for the season of multiple influenzas.

A paper in the science journal Nature this week revealed that every flu season brings an abundance of infective agents. That is why some people come down with a fever and chills despite a flu shot - the vaccine was aimed at a flu virus different from the one they caught.

The paper's authors say the method they used to identify abundant flu virus strains will lead to a better way to monitor avian flu before it becomes a global scourge. "If a strange flu started circulating in a population, then obviously a survey method like our project embodies the way to detect it, hopefully quickly," said Steven Salzberg of the Center for Bioinformatics and Computational Biology at the University of Maryland, one of the paper's authors.

"We wouldn't notice it with today's methods," he said, which only look at viruses when they've already caused alarm.

"I think this is going to be a really important paper," Nick Bergman, a bioinformatics specialist at the University of Michigan, said. He is not associated with the Nature paper. "This paper should really make a difference" in not only tracking virus evolution, he said, but in improved vaccine design.

The key to their work is high-volume genetic analysis. They analyzed flu samples from 209 patients in New York from 1998 to 2004. They expected to find that most people in the same area would have the same flu in a given season, said Elodie Ghedin, lead author on the paper and an assistant investigator with The Institute for Genomic Research, a nonprofit genetic analysis center in Rockville, Md.

"But we saw a lot of other lineages. You and your neighbor would not necessarily have the same flu," Ms. Ghedin said.

By rapidly decoding the genes of 209 virus samples, the researchers saw intimate evidence of flu's rapid evolution. Sloppy replication was responsible for most mutations. Viruses made with RNA instead of DNA, such as flu, are known for careless copying. It's what makes them so adaptable, able to work around one vaccine after another.

But other viral mutations go beyond bad copying. Some change their personalities by swapping genes with another nearby virus. It was such a swap that made the vaccines often ineffective in the 2003-2004 flu season. That season, vaccines were based on a flu type dominant at the end the previous season, as they generally are.

"But two of the [viral] tribes intermarried, and we got a new lineage," Mr. Salzberg said. "The new lineage dominated the following year. The vaccine was mostly ineffective."

If rapid-fire gene decoding were used every flu season, the vaccine designers would have a more accurate idea of what viral types were out there, and which to target for the coming season, he said.

"We think we can do better. The flu shot is not always effective. ... This project, this is how we're going to get a handle on what the flu is doing and what's likely to emerge next year."

Contact Jenni Laidman at:

jenni@theblade.com

or 419-724-6507.



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