One of the most striking features of influenza is perhaps also the most frightening—that strains of the virus can easily pick up genes from one another, through a process known as reassortment.

Today, researchers at MIT release research showing that genetic reassortment within a particular flu strain circulating among birds and pigs could pose a significant health threat to humans, just as it did during summer 1968, when an H3N2 pandemic led to the deaths of an estimated 1 million people.

“There are indeed examples of H3N2 that we need to be concerned about,” MIT’s Ram Sasisekharan, Ph.D., professor of biological engineering, said in a statement. “From a pandemic-preparedness point of view, we should potentially start including some of these H3 strains as part of influenza vaccines.”

In a Scientific Reports study published today, Sasisekharan and his colleagues report on their investigation to evaluate the potential risk of H3N2 strains re-emerging in humans. For this, the researchers compared the deadly 1968 strain with around 1,100 H3 strains now circulating among birds and pigs. Comparing genetic sequences for a particular protein across five key locations that control the viruses’ interactions with infected hosts, they calculated an antigenic index for each strain. Then, searching for those that had an antigenic index of at least 49%, the team identified 581 strains isolated since 2000—549 from birds, 32 from pigs—that demonstrated potential to cause a pandemic.

The researchers then exposed some of those to antibodies provoked by current seasonal-flu vaccines, finding that they did not recognize the H3 strains. Of the 581 pandemic-potential sequences, Sasisekharan said, six strains from pig already have the mutations necessary for human adaptation. “There seems to be a lot more mixing of H3 between humans and swine,” he said.

Sasisekharan’s team is now working on a similar study involving H5 strains, he added.

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