University of Nebraska-Lincoln researchers have developed a vaccine approach against avian influenza that researchers say shows strong early results in animal testing.
According to the U.S. Department of Agriculture, H5N1 has affected more than 206 million birds across all 50 states since February 2022. In March 2024, the virus spread to dairy cattle for the first time. The Centers for Disease Control and Prevention reported the virus has since sickened about 71 farm workers nationwide who had close animal contact.
In Nebraska, the USDA confirmed the state's first dairy cattle H5N1 case in September 2025, and there are still no licensed vaccines to protect cattle anywhere in the world.
The UNL 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. Their findings were published April 21 in npj Vaccines.
Weaver said his concern about the virus began in 2005 following a cluster of infections in Asia, prompting him to begin research. He designed a vaccine based on a centralized gene approach, intended to provide broad protection against multiple H5N1 strains, later updating it to use the same type of delivery technology found in the Johnson & Johnson and AstraZeneca COVID-19 vaccines. He published his last paper on the research around 2015, hoping the virus would no longer pose an immediate threat.
When H5N1 spread to dairy cattle in 2024, the vaccines Weaver had developed over nearly two decades were already sitting in his lab.
"We already had them in the freezer. They existed. So we thought, well, let's see if they'll work," he said.
When the cattle outbreak began, Weaver said he hoped it would resolve on its own.
"Maybe it'll just go away. And then it didn't. At the end of 2024, getting into 2025, I started to get really worried," he said. "So, we were able to find some funding to do a cattle study with these vaccines that I had already designed."
Working with the UNL Animal Care Team, researchers vaccinated eight dairy calves at one week of age using both intramuscular and intranasal delivery. The approach was designed to fight the virus on two fronts. The intramuscular injection builds systemic immunity, protecting the animal if the virus enters its bloodstream. The intranasal delivery targets the mucosal lining of the respiratory tract, the first point of entry for the virus, helping prevent it from spreading from animal to animal.
Weaver said each method serves a distinct purpose.
"Mucosal protects against transmission and the intramuscular protects against disease," he said.
Weaver said vaccinating at one week of age is practical for commercial dairy operations, and the immune response only grows stronger as the animal does.
In parallel mouse trials, vaccinated animals were fully protected against lethal H5N1 infection. Weaver said the contrast between vaccinated and unvaccinated animals was immediately visible.
"When you've got control animals that are unvaccinated, that are more or less dying, they lose 25% of their body weight in five or six days," he said. "It's insane."
But for vaccinated animals, the outcome was completely different.
"The vaccine works so well, it's as if the disease never happened," he said. "The ones that are vaccinated, they actually gain a little weight. It's like nothing ever happened."
Weaver said similar vaccines tested in pigs suggest immunity could last more than a decade, though longer studies in cattle are still needed. Still, he said the ambitions behind the research extend well beyond cattle.
"We would like this vaccine to be a multispecies farm-type vaccine that you could vaccinate your pig, your cow, your goat and your sheep and your chicken and yourself," he said.
Weaver said he is open to working with any pharmaceutical company, whether human or agricultural, through NUtech Ventures, UNL's intellectual property office, to bring the vaccine to market.
He warned that the window to produce a vaccine for cattle before the virus becomes widespread is narrowing.
"This virus isn't supposed to be in cattle, and it's kind of an accident," he said. "But if we give it enough time, it will become established in cattle. We've got a short window to try to get rid of it completely."
For Weaver, Nebraska's agricultural identity makes the research not just important but necessary.
"We were the beef state," he said. "This is a beef issue. I think the University of Nebraska should be a front leader in that type of research."