Flu vaccine candidate may provide universal protection against influenza strains

LINCOLN, Neb. — As summer turns to fall, many Americans may go from thinking about the coronavirus vaccine to thinking about their annual flu shot. Now, a recent study has found a vaccine candidate that may be the closest thing to a universal flu shot. Researchers from the University of Nebraska-Lincoln say this vaccine offers protection against “an unprecedented range of swine flu strains,” including the ones which sparked flu pandemics in 1918 and 2009.

The first flu pandemic of the 21st century hit the world in 2009, with the outbreak of the H1N1/09 swine flu. Nearly 1.4 billion people dealt with that strain of the flu, that is capable of jumping from pigs to humans.

“They’re considered the great mixing vessel. They’re susceptible to their own circulating influenzas, as well as many of the avian and human influenzas,” says Eric Weaver, an associate professor of biological sciences, in a university release.

“If you put an avian, a swine, and a human virus into the same cell, they can swap genome segments. When you mix those viruses in the swine, what pops out could be all swine, or a little human and swine, or a little avian and swine, or a little of all three. And you never know: You might get the perfect combination of parts that makes for a very high-fitness virus that is highly transmissible and new to humans, meaning that people don’t have immunity to it.”

Targeting the most common flu strains

Weaver spent many years trying to create a vaccine capable of killing multiple strains of the flu, including those that have not yet come about. According to his team’s most recent research, they have possibly produced a vaccine that kills over a dozen different swine flu strains.

“This is the best data I’ve ever seen in the (research) literature,” Weaver says of the team’s findings, published in the journal Nature Communications.

In H1N1, “H” stands for the protein hemagglutinin and “N” stands for the protein neuraminidase, both of which sit on the surface of flu viruses. These proteins allow the viruses to break into and leave cells. However, researchers targeted the H3 strain (H3N2) since it has accounted for over 90 percent of flu infections since 2010.

To develop a vaccine that would kill multiple strains of the H3N2 virus, his team used a computer program called Epigraph to create fragments of the proteins on the surface of the virus in order to elicit an immune response. Any fragment would cause the immune system to attack, thereby allowing the body to overcome the viral strains.

Epigraph was able to recreate proteins for every possible variant of the virus. Using the “H” protein structure, it was able to determine the most common amino acid sequences used to develop various strains.

“So what you end up with are the most common epitopes that exist in nature linked together, then the second-most common, and then the third-most common. When you look at it from an evolutionary standpoint, the first resembles what most of the viruses look like. The second starts to look a bit different, and the third looks even more different,” Weaver explains.

“But all three of these make a contribution to the vaccine itself, and they work through slightly different mechanisms.”

Robust response in animal tests

When scientists tested the vaccine on mice and pigs, their immune systems fought off each strain accordingly. The vaccine was more efficient than the commercial FluSure swine vaccine.

For comparison, this vaccine produces specific virus-fighting antibodies for 14 of the 20 strains, whereas FluSure only produces antibodies for four of the 20 strains present. Moreover, vaccinated mice developed increased levels of T-cells which help infected cells die to prevent the rest of the body from being infected.

The Epigraph vaccine seemed to help mice keep viral particles out of their lungs as well as keep up their overall weight. Also, this is the only vaccine to help mice survive a lethal injection of the H3 strain.

The study revealed similar results in pigs with antibodies appearing for 13 of 20 flu strains. One injection of the FluSure vaccine did not stimulate any antibody production in pigs. Additionally, T-cell concentration was higher in those with the Epigraph vaccine.

Now, the team plans to test the vaccine in human trials and to determine the overall length of immunity as well. This vaccine could put an end to flu-strain predicting and ensure relatively universal immunity each year.

“This study is equivalent to a bench-to-bedside study, where the positive results in the preclinical mouse study are confirmed by positive results in a clinical pig study. This gives us confidence that when the concept is applied to human influenza virus, we’ll see the same translation from preclinical studies to clinical studies in humans,” Weaver concludes.