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A mutation may explain why last year’s flu vaccine failed for so many

Last winter’s flu vaccine was, by many standards, a flop. The vaccine was just 18 percent effective at preventing flu-related doctors’ visits, down from the average 60 percent. Now researchers think they know why.

A team from the Wistar Institute in Pennsylvania has pinpointed a mutation in the 2014-15 flu virus that was able to sneak past a vaccinated person’s defense system.

First, a reminder of how flu vaccines work. One vaccine contains multiple inactive strains of the virus. Once administered, the human immune system builds antibodies that recognize these dead flu strains.That way when the active flu virus enters your body, your immune system is able to recognize the invader and defend itself.

The Wistar Institute team focused on a protein called hemagglutin. This protein helps the flu virus bind to healthy cells. Once latched on, the virus can easily infect the host cell. While studying this year’s virulent flu strain, H3N2, biologist Scott Hensley discovered a single mutation in the segment of RNA that codes for this protein. Because of the mutation, the antibodies built in response to the flu vaccine didn’t recognize the virus.

The result: More than 100,000 people were sickened by the flu this past season, according to CDC estimates.

To better understand where future mutations could occur, Hensley’s team created a vaccine that targeted the H3N2 viral mutation and tested its power against flu-infected blood samples. The findings published in the journal Cell Reports show that last year’s vaccine was 75 percent less effective than Hensley’s new vaccine at initiating an immune response against the mutated H3N2 flu strain.

It’s anyone’s guess whether Hensley’s vaccine will be useful during next year’s flu season, since the virus changes so much from year to year. Also, the immune systems of people who recovered from last year’s flu are now equipped to handle re-exposure to that strain. Instead, scientists should focus on possible future mutations in the hemagglutinin region when considering the production of new vaccines, Hensley said.

Scientists use Global Initiative on Sharing Avian Influenza Data to track and share flu virus mutation patterns online. This dataset provided Hensley with a starting point: the world observed 10 different mutations in this past year’s flu virus. Hensley used a technique referred to as reverse genetics.

“We took those mutations and put them back into the vaccine strain one by one and then asked which of those mutations made the vaccine look different to the immune system?” Hensley said.

Twice a year, the World Health Organization meets to predict future flu mutations, once in the northern hemisphere and once in the southern. They look for emerging flu strains with steep rates of infection from 112 countries and pass their report onto the Food and Drug administration (FDA). The FDA then decides which strains to protect against during the next flu season, and then scientists begin making and testing the new vaccine. This past year was a bit of a fluke, Hensley said: “Usually they get it right.”