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UW Flu Research

By accurately predicting how flu viruses might mutate, UW-Madison researcher Yoshihiro Kawaoka could help the World Health Organization develop vaccines that are better suited to fight as-yet unknown strains of the disease.

A UW-Madison scientist says a method he developed to predict flu virus mutations could make the annual flu vaccine more effective by better matching it to the flu strains that circulate each flu season.

The development by virologist Yoshihiro Kawaoka follows research he did last year suggesting another way to improve flu shots: manufacturing them with dog or monkey cells instead of the current, lengthy process using chicken eggs.

Kawaoka’s findings come despite an effective ban on some of his research, which started in October 2014. The government asked him and others to stop studies that raised concerns about biosecurity during a review of the risks and benefits.

The National Science Board for Biosecurity, which is overseeing the review, meets Tuesday in Bethesda, Maryland, to discuss recommendations for oversight of the research.

Known as “gain-of-function” research, the studies involve altering flu viruses and other pathogens in the lab to make them more deadly or spread more easily, generally in an effort to develop vaccines or prepare for pandemics.

Some of the new research about predicting flu virus mutations, reported Monday in the journal Nature Microbiology, is considered “gain-of-function.” But Kawaoka and Rebecca Moritz, a campus biosafety manager, said the National Institutes of Health approved it.

The work reported last year, related to dog or monkey cells, involved virus engineering research covered by the “gain-of-function” ban. Kawaoka said he conducted that study before the ban.

The new research could help solve a problem related to the way flu vaccines are made. It takes six months or more to produce the vaccine, so health officials select the three or four strains to be covered each year in February, well before the next flu season starts.

But viruses can mutate, leading to a poor match. This happened in 2014-15, when the vaccine was only 23 percent effective, according to the Centers for Disease Control and Prevention. In 2015-2016, it was 59 percent effective.

In his lab, Kawaoka mixed flu viruses carrying a range of mutations with antibodies like those that offer protection in vaccines. For the viruses that had enough mutations to evade the antibodies, he mapped their patterns of mutation.

Such mapping could predict the molecular characteristics of upcoming flu viruses, he said. That could allow the World Health Organization, which selects virus strains to be used in the vaccine, to choose strains with the expected mutations.

“This is the first demonstration that one can accurately anticipate in the lab future seasonal influenza strains,” Kawaoka said in a statement. “We can identify the mutations that will occur in nature and make those viruses available at the time of the vaccine (virus) candidate selection.”

Some of the co-authors of the new research paper are members of the WHO strain selection committee, Kawaoka said, so “the information we provide will likely be considered at the meetings.”

The approach allowed Kawaoka and his colleagues to assemble the 2014 flu virus before the onset of the epidemic, UW-Madison said in a news release.

In the study reported last year, Kawaoka used a process called reverse genetics to generate flu strains that could grow well in dog or monkey kidney cells, which regular flu viruses generally don’t do.

Most flu vaccines approved in the United States are egg-based. Only one uses the method Kawaoka studied, called a cell-based vaccine.

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David Wahlberg is the health and medicine reporter for the Wisconsin State Journal.