Research offers hope for a universal flu vaccine

Imagine a single dose of vaccine that prepares your body to fight every known strain of influenza — a socalled universal flu vaccine that scientists have tried to create for decades.

A new study describes successful animal tests of just such a vaccine, offering hope that the country can be protected against future flu pandemics. Like the covid vaccines made by Pfizer-BioNTech and Moderna, the experimental flu vaccine relies on mRNA.

It is in early stages — tested only in mice and ferrets — but the vaccine provides important proof that a single shot could be used against an entire family of viruses. If the vaccine succeeds in people, the approach could be used against other virus families, perhaps including the coronavirus.

The vaccine would not replace annual flu shots but would provide a shield against severe disease and death from potential pandemic threats.

“There’s a real need for new influenza vaccines to provide protection against pandemic threats that are out there,” said Scott Hensley, an immunologist at the University of Pennsylvania, who led the work.

“If there’s a new influenza pandemic tomorrow, if we had a vaccine like this that was widely employed before that pandemic, we might not have to shut everything down,” he said. He and his colleagues described the vaccine in the Nov. 24 journal Science.

By the age of 5, most children have been infected with the flu multiple times and have gained some immunity — but only against the strains they have encountered.

“Our childhood exposures to influenza lay down longlived immune memory that can be recalled later in life,” Hensley said. But “we’re sort of living the rest of our life dependent on the random chance of whatever we got infected with as a kid.”

Current influenza vaccines protect against seasonal flu but would provide little protection against a new strain that may emerge as a pandemic threat. During the 2009 H1N1 swine flu pandemic, for example, the conventional vaccine offered little defense against the virus. But older adults who had been exposed to H1N1 strains in childhood developed only mild symptoms.

Scientists have long tried to create a vaccine that would introduce children to every possible strain of flu they may encounter later in life. But researchers have been constrained by technical hurdles and by the diversity of the flu virus.

Broadly speaking, there are 20 subgroups of influenza that each represent thousands of viruses. Current vaccines can target four subgroups at most. But the experimental vaccine contains all 20, and it would be faster to produce.

The vaccine elicited high levels of antibodies to all 20 flu subtypes in ferrets and mice, the researchers found — a finding that several experts said was unexpected and promising.

If the vaccine behaves similarly in people, “we’ll have a more broad coverage of influenza viruses — not only those that are circulating, but those that might spill over from the animal reservoir that might cause the next pandemic,” said Alyson Kelvin, a vaccinologist at the University of Saskatchewan in Canada.

Packing 20 targets into one vaccine does have a downside: Antibody levels in the test animals were lower than when they were given vaccines aimed at individual strains. But the levels were still high enough to be effective against influenza.

Because a new pandemic strain of influenza might differ from the 20 targets included in the experimental vaccine, the researchers also tested it against viruses that were imperfectly matched. The vaccine still provided strong protection, suggesting that it would prevent at least severe illness, if not infection, from a novel pandemic flu virus.

This phenomenon is akin to that with the current covid vaccines: Although the latest omicron variants are so different from the ancestral virus that the original vaccine does not prevent infections, it continues to help safeguard most people against severe illness.

This quality may be a particular advantage of mRNA vaccines, Kelvin said. Conventional flu vaccines target only the specific viruses they are designed for. But mRNA vaccines seem to produce antibodies that defend the body against a broader range of viruses than those included.

The experts noted some important caveats and questions that must be answered before the vaccine becomes a viable candidate.

The animals in the study built defenses against all 20 flu strains equally. But “these animals have not seen flu before,” said Richard Webby, an expert in influenza viruses at St. Jude Children’s Research Hospital in Memphis.

Such a complete lack of immunity against flu is only true of very young children, Webby noted. Older people are exposed to many different strains over their lifetimes, and it’s not clear whether their immune responses to a universal vaccine would be quite so uniform.

“The proof of the pudding will be what happens when it goes into humans and how going into a pre-immune population skews the response to it,” Webby said.

Designing universal vaccines for varying age groups, if necessary, would be a challenge. It would also be important to see how long protection from such a vaccine lasts, some experts said.

“The biggest issue about universal flu is what you need to target and how long you can continue to use the same vaccine,” Ted Ross, director of Global Vaccine Development at the Cleveland Clinic, said. “If you have to keep updating it, it may not increase the advantage of how we do vaccines today.”

The next step for the vaccine would be to test it in monkeys and in people. But proving its effectiveness might be challenging. “How do you evaluate and regulate a vaccine where their targets aren’t circulating, and so you can’t really show effectiveness?” Kelvin said.

Perhaps the vaccine could be tested in small sporadic outbreaks, or in poultry workers who are at risk of becoming infected with an avian flu virus, she said: “Those are questions that I think we need to answer before we have our next pandemic.”

Scientists have long tried to create a vaccine that would introduce children to every possible strain of flu they may encounter later in life. But researchers have been constrained by technical hurdles and by the diversity of the flu virus.