Imagine a single dose of vaccine that primes your body to fight every known strain of influenza—a so-called universal flu vaccine that scientists have been working on developing for decades.
A new study describes successful animal testing of such a vaccine and offers hope that the country can be protected from future influenza pandemics. Like the Covid vaccines made by Pfizer-BioNTech and Moderna, the experimental flu vaccine is mRNA-based.
It’s in the early stages – tested only in mice and ferrets – but the vaccine provides important evidence that a single vaccine could be used against an entire family of viruses. If the vaccine is successful in humans, the approach could be used against other virus families, potentially including the coronavirus.
The vaccine would not replace annual flu shots, but would provide protection against serious illness and death from potential pandemic threats.
“There is a real need for new influenza vaccines to provide protection against the 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 flu pandemic tomorrow, if we had a vaccine like this that was widely available before this pandemic, we might not have to shut everything down,” he said. He and his colleagues described the vaccine in the journal Science last week.
By the age of 5, most children have contracted the flu several times and gained some immunity—but only to the strains they’ve encountered.
“Our childhood exposure to influenza sets up a long-lived immune memory that can be recalled later in life,” said Dr. Hensley. But “we live the rest of our lives depending on the chance of what we contracted as a child.”
Current influenza vaccines protect against seasonal flu but would offer little protection against a new strain that could emerge as a pandemic threat. For example, during the 2009 H1N1 swine flu pandemic, the conventional vaccine offered little protection against the virus. But older adults exposed to H1N1 strains in childhood developed only mild symptoms.
Scientists have long tried to create a vaccine that would introduce children to all the possible strains of flu they might encounter later in life. But the researchers were limited by technical hurdles and by the diversity of the flu virus.
Broadly speaking, there are 20 subgroups of influenza, each representing thousands of viruses. Current vaccines can target at most four subgroups. But the experimental vaccine contains all 20 and would be quicker to make.
The vaccine elicited high levels of antibodies against all 20 influenza subtypes in ferrets and mice, the researchers found — a result several experts said was unexpected and promising.
If the vaccine behaves similarly in humans, “we will have broader coverage of influenza viruses — not just those that are circulating, but also those that are spilling out of the animal reservoir and could cause the next pandemic,” Alyson Kelvin, a vaccinator at the University of Saskatchewan in Canada, said.
Packing 20 targets into one vaccine has a downside: antibody levels in the test animals were lower than when vaccines that targeted single strains were administered. But the levels were still high enough to be effective against influenza.
Because a new pandemic influenza strain could differ from the 20 targets of the experimental vaccine, the researchers also tested it against viruses that weren’t perfectly matched. The vaccine still provided strong protection, suggesting it would at least prevent serious illness, if not infection, from a novel pandemic flu virus.
This phenomenon is similar to that seen with current Covid vaccines: although the latest Omicron variants are so different from the ancestral virus that the original vaccine fails to prevent infection, it continues to help protect most people from serious illnesses.
This quality could be a particular advantage of mRNA vaccines, said Dr. Kelvin. Traditional flu vaccines only target the specific viruses for which they are designed. But mRNA vaccines appear to produce antibodies that protect the body against a broader range of viruses than those contained.
The experts identified some important caveats and questions that need to 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 never seen the flu,” said Richard J. Webby, an influenza virus expert at St. Jude Children’s Research Hospital in Memphis.
Such a complete lack of immunity to influenza only applies to very young children, noted Dr. Webby tight. Older people are exposed to many different strains throughout their lives and it is not clear whether their immune response would be as uniform to a universal vaccine.
“The proof of the pudding will be what happens when it gets into humans and how entering a preimmune population distorts the response to it,” said Dr. Webby.
Developing universal vaccines for different age groups, if needed, would be a challenge. It would also be important to see how long protection from such a vaccine lasts, some experts said.
“The biggest problem with universal flu is what to target and how long you can keep using the same vaccine,” said Ted Ross, director of global vaccine development at the Cleveland Clinic. “If you have to keep updating it, it may not increase the benefit of how we make vaccines today.”
The next step for the vaccine would be to test it on monkeys and humans. However, proving its effectiveness could be a challenge. “How do you evaluate and regulate a vaccine where its targets aren’t circulating and therefore you can’t really demonstrate its effectiveness?” said Dr. Kelvin.
Perhaps the vaccine could be tested on small sporadic outbreaks or on poultry workers at risk of contracting an avian flu virus, she said: “Those are questions I think we need to answer before we have our next pandemic.”