Researchers at the University of Nebraska–Lincoln have developed a vaccine approach that shows promise in protecting against highly pathogenic bird flu, demonstrating strong efficacy in both mice and cattle.
Avian influenza, or H5N1, has disrupted agricultural systems globally, leading to the culling of more than 166 million commercial poultry birds in the United States since 2022. In 2024, the virus spread to dairy cattle — an unprecedented interspecies transfer — and subsequently caused illness in about 70 farm workers with close contact to infected animals.
The vaccine research was led by virologist Eric Weaver, professor of biological sciences and director of the Nebraska Center for Virology, along with postdoctoral fellows Joshua Wiggins and Adthakorn Madapong in the School of Biological Sciences. Their findings are forthcoming in NPJ Vaccines. The new vaccine platform is designed to protect against multiple H5N1 strains and to generate immunity in both the bloodstream and the respiratory tract.
The vaccine was tested in mice and dairy calves, producing strong immune responses and complete protection against severe disease in preclinical models. The results suggest the approach could offer protection for livestock, particularly because there are currently no licensed H5N1 vaccines for cattle.
Weaver said the team built on earlier work from his lab when the cattle outbreak began.
"I had started working on this as a potential problem in 2005, but the last publication was around 10 years ago," Weaver said. "When the outbreak began, my hope was that this would cycle through dairy cattle and be gone, but that didn't happen. It got progressively worse and I was worried."
Working with the animal care team at Nebraska, the researchers obtained calves for testing in early 2025. The calves were vaccinated at one week of age using a combination of intramuscular and intranasal delivery and received a booster four weeks later. In a separate experiment, vaccinated mice were fully protected against lethal infection from multiple H5N1 strains.
"The idea was that if we put it intramuscularly, we can prevent it from spreading in the body, and then a mucosal aspect, intranasally, would prevent it from spreading from animal to animal," Weaver said.
With these new findings, Weaver is seeking funding and potential partnerships to further evaluate the vaccine, including development of a multispecies option. Protecting cattle from H5N1 could reduce economic losses for producers while also limiting opportunities for the virus to adapt and spread to humans.
"We'd like to have a vaccine for the farm and the farmer, and everything shows that this would be an effective vaccine platform for humans as well," Weaver said.
As diseases continue to cross species barriers, Weaver said research like this will be critical to protecting Nebraska and the global community.
"Historically, these things will move into other species if there is extended contact long enough for the evolution to occur," he said. "Influenza A viruses have never been an issue in cattle, but it is now, and it's not going away."
