Rare flu mutation might lead to new vaccine

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A rare and improbable mutation in a protein encoded by an influenza virus makes it unable to defend itself against the body’s immune system.

Scientists say the discovery could provide a new strategy for live influenza vaccines in the future.

A new approach to the live flu vaccine would be particularly advantageous, since the Centers for Disease Control and Prevention stopped recommending using the live attenuate flu vaccine, FluMist earlier this year. Several studies found that the pain-free nasal spray, which was used in about one-third of young children in the United States offered no protection to that especially vulnerable population. The flu shot, on the other hand, performed well and the CDC recommends using this vaccine instead.

“There is a need to understand what’s happening with the existing live vaccine and potentially a need to develop a new one,” says David Topham, professor of microbiology and immunology at the University of Rochester Medical Center. “We proposed that the mutation we found could be used to create a live vaccine.”

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The new mutation weakens the flu virus by making the flu-encoded protein, called Non-Structural 1 (NS1), defunct. Flu virus needs NS1 to prevent interferon, the immune system’s front line against viruses, from alerting the host cell that it has been infected. Inhibiting interferon gives the virus time to multiply and spread before the immune system can mount an attack.

Most people have healthy interferon responses and would quickly and easily fend off this weakened mutant strain of flu, but, “this virus somehow managed to find the one person that had an interferon defect that allowed it to replicate,” Topham says.

The probability of the virus surviving and infecting a human is so low—sort of like finding a needle in a haystack. Topham and lead author, Marta Lopez de Diego, research assistant professor of microbiology and immunology, isolated the mutated virus from a nasal swab of a single flu sufferer who happened to be among the small percentage of people with inadequate interferon responses. When they looked for the NS1 mutation in a national database, it showed up in just 0.03 percent of all flu strains reported.

The “attenuating” flu mutation could provide a new way to make live flu vaccines, which contain viruses that are alive, but weakened, so the vaccine itself doesn’t cause illness in people. The researchers suspect the mutation could be a great way to prevent viruses in the live vaccine from infecting anyone who has normal interferon responses, which is most people.

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The study, published in the Journal of Virology, also highlights the importance of flu virus surveillance—conducting studies to see how the flu is changing, what flu mutations are circulating in humans and animals, and how those mutations affect virus function.

Topham says health leaders aren’t doing enough of that kind of research. “The influenza field is largely fixated on studying pandemic or potential pandemic viruses, but those viruses only infect a few dozen people every year whereas seasonal flu infects millions—and yet we don’t study human influenzas closely enough.”

The World Health Organization estimates there are 1 billion flu infections each year, causing 300,000 to 500,000 deaths.

Until recently, researchers believed that proteins like NS1 didn’t change much from strain to strain and season to season, but the new findings show that NS1 mutations occur naturally and can affect its ability to suppress immunity. Monitoring for these mutations in nature could help produce better vaccines that save more lives.

Source: University of Rochester