• Posted April 20, 2023

Scientists Get Closer to a 'Universal' Flu Vaccine

Researchers are reporting progress on the path to a "universal" flu vaccine -- one that would battle all strains of the virus and give the world a weapon against future flu pandemics.

In an early clinical trial, U.S. government scientists found that their experimental flu vaccine was able to coax recipients' immune systems to produce "cross-reactive" antibodies. That is, they made antibodies against many strains of influenza type A -- one of the two major groups of the virus.

Experts called the findings promising, in that the vaccine did exactly what you'd want in this early phase of testing.

However, it has not yet been shown to actually protect people from the flu, stressed researcher Sarah Andrews of the U.S. National Institute of Allergy and Infectious Diseases' Vaccine Research Center.

She estimated that it could take five to 10 more years of development before, if all goes well, the vaccine is ready for the real world.

Right now, the available flu vaccines prime the body to fight four flu strains: two type A influenza strains, and two type B.

The problem is, there are many strains within those two groups, and different ones are in high circulation each flu season. So the flu vaccine has to be updated annually to include the four strains that scientists think are likely to dominate in the upcoming season.

It's essentially an educated guess.

"And that guess isn't always correct," said Dr. Mirella Salvatore, an associate professor at Weill Cornell Medicine in New York City, and a spokeswoman for the Infectious Diseases Society of America.

Salvatore, who was not involved in the new research, said that a universal flu vaccine could not only get rid of the yearly guessing game, but also help arm people for the next flu pandemic.

Several such vaccines are in various stages of development. The one Andrews and her colleagues are working on has now passed an early test, according to Salvatore.

"They're showing it produces an antibody response, and the antibodies last a long time," she said.

One year after being vaccinated, study participants were still showing neutralizing antibodies against type A flu strains, according to findings published April 19 in the journal Science Translational Medicine.

There are various reasons a universal flu vaccine has been elusive, but the fundamental obstacle is the complexity of the influenza virus.

The new vaccine, Andrews explained, was designed to get around a key barrier.

Current flu vaccines contain weakened or inactivated flu viruses with a mix of hemagglutinins (HAs), a major protein on the surface of the virus. When people get a flu shot, or the flu, the immune system creates antibodies against HA -- specifically against the top portion, or "head," of the protein.

That's a problem, however, because portions of the HA head often mutate, feeding the need for that yearly vaccine update.

But HA not only has a head -- it has a "stem." And that stem stays relatively stable and "conserved" across the different flu strains.

Getting the immune system to respond to the stem, however, is tricky, Andrews said. Folks' immune systems are primed -- by a lifetime of flu virus exposures -- to go full-tilt at the HA head, leaving the stem ignored.

So Andrews and her colleagues tried a new tactic: They lopped off the protein's head. They then replaced it with an engineered top of sorts, designed to give the stem stability but not draw the immune system's ire.

"The only thing the immune system can see is the stem," Andrews said.

To put the headless HA to an initial human test, the researchers recruited 52 healthy adults and gave each either of two vaccine doses. Most received the higher dose, given as a primary shot followed by a booster.

First and foremost, the vaccine looked safe, the researchers found. About one-fifth of recipients had soreness at the injection site or a headache -- standard flu shot side effects.

As for their immune response, participants showed a broad antibody response against type A flu strains -- though not type B. That's expected, Andrews explained, because the vaccine contained HA from a type A strain.

A "bivalent" vaccine (one that contains HA from both influenza groups) would be expected to have "increased breadth," the researchers said.

Dr. Aaron Glatt, an infectious disease specialist not involved in the trial, agreed that the initial immune responses look promising.

He likened the vaccine approach to an ice cream cone. Instead of targeting each of the 32 flavors of ice cream it could contain, "you go after the cone," said Glatt, who is chief of infectious diseases at Mount Sinai South Nassau in Oceanside, N.Y.

If a universal flu vaccine becomes available, no one knows exactly what the regimen would look like, Glatt said: Would people still have to get it once a year, or less often, for example?

Plus, it would not necessarily keep people from getting sick at all. All of the experts said that a vaccine that substantially protects against severe flu would be a "win."

More information

The U.S. Centers for Disease Control and Prevention has more on flu vaccination.

SOURCES: Sarah Andrews, PhD, staff scientist, Vaccine Research Center, U.S. National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Aaron Glatt, MD, chief, infectious diseases, and hospital epidemiologist, Mount Sinai South Nassau, Oceanside, N.Y., and professor, medicine, Icahn School of Medicine at Mount Sinai, New York City; Mirella Salvatore, MD, associate professor, medicine, Weill Cornell Medicine, New York City; Science Translational Medicine, April 19, 2023, online