Penn scientists have made a universal flu vaccine using mRNA, and they plan to test it in humans

For years, scientists have tried, unsuccessfully, to make a single vaccine that would provide at least partial protection against all types of flu.

A University of Pennsylvania scientist now thinks he’s cracked the case, using the same technology that was the basis of the Pfizer and Moderna COVID vaccines: messenger RNA.

In November, Scott Hensley and his colleagues announced promising results testing this universal flu vaccine in lab animals, and they are now considering testing it in humans.

The vaccine would not replace annual flu shots, which are tailored to the flu strains circulating that year. Instead, it would offer a basic level of protection against the broader 20 types of flu – probably not preventing infection in most cases, but significantly reducing the risk of serious illness, said Hensley, professor of microbiology at Penn’s Perelman School of Medicine.

“Can we make a vaccine that primes our immune system against all flu subtypes, including those that are already circulating in humans and also those that haven’t crossed over into animals?” He asked. “That’s really our goal here.”

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When scientists tried to make universal flu vaccines in the past, the formulas usually consisted of fragments of ancestral proteins that all flu viruses have in common. For various reasons, the immune system has not formed a robust response to this lowest common denominator approach.

Hensley’s vaccine, on the other hand, consists of proteins from all 20 different types of influenza — or technically, the recipe for the recipient to make those proteins, spelled out with the four building blocks of mRNA.

This concept was first developed two decades ago by two of Hensley’s colleagues at Penn, Drew Weissman and Katalin Karikó, who won wide acclaim during his first real-world success, the Pfizer and Moderna vaccines against the COVID. Weissman is also among Hensley’s collaborators on the universal flu vaccine, and separately he is working on various vaccines that would protect against multiple coronaviruses.

Scientists not involved in the flu vaccine experiments, the results of which have been published in Science, say the Penn team’s approach looks promising.

In addition to allowing the inclusion of 20 different types of proteins, mRNA vaccines can be made faster than traditional vaccines. It’s a plus if recipes need to be changed in the event of a pandemic, University of Saskatchewan scientists Alyson A. Kelvin and Darryl Falzarano wrote in a commentary published in the same journal.

But getting such a vaccine approved can be a challenge, according to Sarah Cobey, a professor of viral ecology and evolution at the University of Chicago. The FDA typically requires a pharmaceutical company to demonstrate that a vaccine prevents infections, which would be difficult to demonstrate when most types of flu aren’t in circulation, she told STAT, a media outlet specializing in influenza. health and science.

“The path to getting a license doesn’t seem straightforward to me,” she said.

Still, she said the Penn flu vaccine results were encouraging.

In addition to ease of manufacture, another advantage of the mRNA approach is that it appears to overcome a problem called original antigenic sin, Hensley said.

What this means requires a bit of explanation:

The immune system forms a lasting memory of the first time it encounters a virus or a vaccine based on that virus. This initial imprint is so strong that if a person is later vaccinated against a different form of the virus, their immune system may still respond with antibodies that more closely match the initial exposure.

Call it the challenge of teaching an old dog new tricks, immune system editing.

But with Hensley’s Universal Vaccine, when lab animals were exposed to fragments of all 20 flu varieties at once, their immune systems seemed to form equally strong and lasting memories of all 20.

The approach seemed to work both in animals that had never been exposed to any type of flu and in those that had been exposed before. In other words, the 20-flavor-at-a-time approach seems able to replace strong initial memories—a phenomenon that Hensley and members of his lab have jokingly called “absolution” from original “sin.”

“If the vaccine is given early in childhood, it can provide an early blessing of induced immunity,” he said. “And perhaps this vaccine is also useful for the absolution of original antigenic sin.”