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One of the main circulating influenza viruses has changed and the current flu vaccines don’t match it well any more – an indication they may not do much to prevent infection, researchers reported Thursday. But they are still likely to prevent severe illness.

“From our lab-based studies it looks like a major mismatch,” Scott Hensley, a professor of microbiology at the University of Pennsylvania who led the study, told CNN.

It’s bad news for the vaccine, he said. Influenza vaccines protect against four different strains of the flu: H3N2, H1N1 and two strains of influenza B. Hensley’s study only covers H3N2, but that happens to be the main circulating strain.

The vaccine mismatch may help explain an outbreak of flu at the University of Michigan last month that affected more than 700 people. More than 26% of those who tested positive had been vaccinated against flu – the same percentage as those who tested negative. That indicates the vaccine was not effective in preventing infection.

It’s what flu viruses do, Hensley said. “We have been monitoring this virus for several months,” he said. Flu viruses mutate all the time—far more than other viruses, including the coronavirus. And different variations can circulate at the same time. But this version of H3N2 has changes that help it escape the antibodies the body makes in response to vaccines.

Antibodies are the first line of defense against invaders like viruses, and the current vaccine doesn’t seem to generate any of the right antibodies against this new, mutated version of H3N2, called 2a2 for short.

Luckily, the changes are unlikely to affect the second line of defense offered by immune system – cells called T-cells, so even if the vaccines don’t protect against infection, they are likely to protect people against severe disease and death, Hensley said.

“Studies have clearly shown that seasonal influenza vaccines consistently prevent hospitalizations and deaths even in years where there are large antigenic mismatches,” Hensley and colleagues wrote in a report posted online as a pre-print. It’s not published in a peer reviewed journal.

“Influenza vaccinations will be crucial for reducing hospitalizations as SARS-CoV-2 and 2a2 H3N2 viruses co-circulate in the coming months.”

The US Centers for Disease Control and Prevention has said influenza virtually disappeared last year, but it’s coming back this year. The big fear is a “double whammy” of flu and Covid-19.

“Population immunity against influenza viruses is likely low since these viruses have not circulated widely during the COVID-19 pandemic,” Hensley’s team wrote.

“Social distancing, mask wearing, and decreases in international travel have likely contributed to reduced global circulation of influenza viruses. Once COVID-19-related restrictions are eased or lifted, it is possible that influenza viruses will circulate widely due to lack of infection-induced population immunity over the past two years.”

Flu vaccine efficacy changes from year to year. Part of the problem is the lead time needed to make influenza vaccines. Most are made using old technology that requires the use of chicken eggs incubated for weeks. So vaccine strains are chosen six months ahead of when the vaccines will be delivered.

The virus can evolve in that time, or different strains can come to dominate, and that appears to have happened this year, Hensley said. In years that the vaccine doesn’t match the circulating viruses well, vaccine effectiveness plummets – sometimes to as low as 6%, as overall effectiveness was against H3N2 flu in the 2014-2015 flu season, according to the CDC.

The changes in the H3N2 virus this year are reminiscent of the mutations that rendered the vaccine so weak in 2014-2015, Hensley said.

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Things can still change, the researchers noted.

“While cases of 2a2 H3N2 infections are quickly rising in the United States and other parts of the world, it is possible that other clades of H3N2 will become predominant in the future,” they wrote.

“It is also possible that H1N1 or influenza B viruses might dominate later in the 2021-2022 season.” It’s not yet clear how well the vaccines might match those strains.

According to the CDC, influenza kills anywhere between 12,000 and 52,000 people a year, depending on the flu season, and puts as many as 700,000 people into the hospital.