Leslie Reed, May 12, 2025
Nebraska-developed vaccine protects against swine, human and bird flu
Annual flu shots could become a thing of the past under a new vaccine strategy developed and tested by University of Nebraska–Lincoln virologist Eric Weaver and his laboratory team.
Research findings published April 29 in Nature Communications reveal a possible breakthrough. The study, “Epitope-Optimized Vaccine Elicits Cross-Species Immunity Against Influenza A Virus,” describes a vaccine that protects against H1N1 swine flu and can also protect against influenza in humans and birds.
“This research sets the stage for developing universal influenza vaccines so people won’t have to go to the doctor and get a flu shot every year,” Weaver said. “This vaccine will protect you against the different strains that are out there.”
Swine vaccinated with the immunogens designed in Weaver’s laboratory exhibited no signs of illness after being exposed to a commonly circulating flu strain; developed antibodies against a multitude of viruses from several decades and multiple species; and maintained their immune response throughout the six-month longitudinal study.
Post-experiment regression analysis indicated that the immunity would not dissipate for a decade, Weaver said.
The Epigraph vaccine, named after computer software used to design it, significantly outperformed a commercial vaccine used by the pork industry and a “wild type” vaccine based on naturally occurring strains with similar immunogens.
The study was supported by the U.S. Department of Agriculture’s National Institute of Food and Agriculture, along with the National Institutes of Health.
The newly published results confirm previous research that demonstrated the vaccine design protected against the H3 influenza subtype. The new results are particularly encouraging, Weaver said, because H1 swine flu variants are detected twice as often as H3 variants — and have nearly three times more genetic diversity.
“This H1 subtype is the largest and most genetically diverse subtype in pigs,” Weaver said. “It’s also among the viruses that jumped from swine to humans to cause the 2009 swine flu pandemic. It’s a big target and one of the harder targets to hit.”
The influenza A virus regularly infects as much as 15% of the human population and causes thousands of deaths each year. Current vaccines often fail to provide long-lasting protection because of the genetic diversity and rapid mutation of proteins that help form the virus. The H1 and H3 subtypes, for example, reflect different mutations of hemagglutinin, the molecules of protein and carbohydrate that coat the surface of a virus and enable it to infiltrate the body’s cells.
Another challenge in controlling influenza is that it infects multiple species: birds, swine, horses and dogs, along with humans. Swine often act as a mixing vessel because they are susceptible to human and bird flu variants, contributing to the evolution of novel forms of the disease that can be transmitted back to humans.
The 2009 swine flu pandemic, for example, resulted from a zoonotic transmission from hogs to humans. About 25% of the human population was infected with the new variant and more than a half million people died from it in the first year, according to some estimates. The 1918 Spanish Flu, 1957 Asian Flu and 1968 Hong Kong Flu pandemics also resulted from cross-species transmission to humans.
“If we can prevent influenza in swine, we can also prevent zoonotic jumps from avians to swine to humans, or from swine directly to humans. We could basically cut off this evolutionary arsenal or advantage that the virus has,” Weaver explained. “The ultimate goal is to eliminate or eradicate influenza.”
Weaver’s vaccine strategy, which has been patented, used the Epigraph software to analyze the genetic codes of more than 6,000 strains of influenza virus occurring from 1930 to 2021 and create a vaccine cocktail representing their most common epitopes.
Epitopes are regions on a virus that trigger the immune system to produce antibodies to neutralize the virus and to send T-cells to destroy infected cells. As the virus evolves, some epitopes disappear, thus evading the immune response. The computationally derived Epigraph strategy increases the likelihood that the vaccine contains the epitopes needed to trigger an immune response and prevent illness.
Data analysis showed the vaccines provided protection for human influenza varieties that emerged during the last 20 years and for swine influenza varieties that emerged over the past century.
“That’s an incredibly powerful thing,” Weaver said. “The ultimate goal would be to have a significant impact on the disease burden in our society.”
Weaver said he believes vaccine science is on the precipice of a major leap forward, thanks in part to improvements in gene sequencing technology and databases.
“Our ability to understand how viruses evolve has increased exponentially in the past 20 years,” he said. “What I see on the horizon is a third wave, where we go from good vaccines to universal lifelong vaccines.”
In the swine study, four groups of five pigs were vaccinated with Epigraph, wild type, commercial or sham vaccines.
Functional antibodies were measured against four swine flu clades, including the 2009 swine flu pandemic variant, two representative human H1N1 strains from the 2009 pandemic and a representative bird flu strain. Epigraph-vaccinated pigs reached threshold immunity levels for all 12 strains tested, while wild type-vaccinated pigs showed immunity against eight of 12 strains. The commercially vaccinated pigs had antibody responses three to five times lower than those observed in the Epigraph and wild type-vaccinated pigs, reaching threshold levels in only six of 12 strains tested. Importantly, the swine study also showed that the Epigraph vaccine induced significantly higher T-cell responses.
Next steps include testing a vaccine to protect against both H1 and H3 strains of influenza. Weaver hopes eventually to form a partnership with a biotechnology company to pursue a human vaccine. Although the results so far have been gratifying, Weaver said he is eager to see if other scientists confirm his results.
“We do the most stringent controls that we can possibly do, because we want to be absolutely certain — and I have no doubt that this vaccine is better than the current vaccines,” he said.
