A new experimental flu vaccine generated high levels of antibodies against all 20 influenza subtypes in early animal tests, results experts say are "unexpected and promising" and could help prevent future pandemics if a novel flu virus emerges, Apoorva Mandavilli writes in the New York Times.

A new universal flu vaccine shows promise

According to Mandavilli, there are 20 subgroups of influenza that each contain thousands of different viral strains. Because there are so many flu strains, it can be difficult to build immunity against all of them, whether through infection or vaccination.

Although most children will have gained some immunity against the flu by the age of five, they are only protected against the strains that they have encountered.

"Our childhood exposures to influenza lay down long-lived immune memory that can be recalled later in life," said Scott Hensley, an immunologist at the University of Pennsylvania. 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."

In addition, current vaccines, which are updated seasonally, can only target up to four influenza subgroups at a time. While these vaccines are likely to be effective against currently circulating flu strains, they would provide little protection against a novel flu virus, including one that could lead to a new pandemic.

However, scientists may now be one step closer to a viable universal flu vaccine, which will be able to protect against every known strain of influenza.

In a new study published in Science, Hensley and his colleagues describe successful animal tests of a universal flu vaccine. Much like Pfizer-BioNTech's and Moderna's Covid-19 vaccines, the experimental flu vaccine was created with mRNA technology.

According to the researchers, the experimental vaccine generated high levels of antibodies against all 20 flu subtypes in mice and ferrets—a finding that several experts called "unexpected and promising," Mandavilli writes.

Although the antibody levels were lower with a single vaccine compared to separate vaccines targeting the individual strains, the levels were still high enough to be protective. In addition, the researchers tested the vaccine against imperfectly matched viruses and found that it still offered strong protection, which suggests it would at least prevent severe illness against a novel flu virus.

If the vaccine is similarly effective in humans, "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.

"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," Hensley said.

The next steps for the universal flu vaccine

Currently, the universal flu vaccine is still in its early stages, and experts say that "some important caveats and questions … must be answered before the vaccine becomes a viable candidate," Mandavilli writes.

Although the animals in the study generated antibodies against all 20 flu strains equally, "these animals have not seen flu before," said Richard Webby, an influenza expert at St. Jude Children's Research Hospital.

According to Webby, only very young children would have a similar complete lack of immunity against the flu, so it's unclear whether older people, who have been exposed to several flu strains, would have the same immune response to the universal flu vaccine.

"The proof of the pudding will be what happens when it goes into humans and how going into a preimmune population skews the response to it," Webby said.

However, experts say that designing universal vaccines for different age groups would be challenging. It is also important to determine how long protection from a universal vaccine would last.

"The biggest issue about universal flu is what you need to target and how long you can continue to use 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 advantage of how we do vaccines today."

After these initial animal tests, the vaccine will need to be tested in monkeys and in people. However, some experts are skeptical whether its effectiveness can truly be tested. "How do you evaluate and regulate a vaccine where their targets aren't circulating, and so you can't really show effectiveness?" Kelvin said.

Some potential options include testing the vaccine in small sporadic outbreaks or in poultry workers who are at risk of avian flu infection, but "[t]hose are questions that I think we need to answer before we have our next pandemic," she said. (Mandavilli, New York Times, 11/29)