PRINCE ALBERT — Dairy cows build a natural immunity to H5N1 after initial infection according to research conducted at the University of Saskatchewan (USask).
When highly pathogenic avian influenza (HPAI) H5N1 was detected in U.S. dairy cattle in March 2024, it sparked a wave of research.
Scientists at USask’s Vaccine and Infectious Disease Organization (VIDO) set out to understand how the virus affects cows and whether natural immunity could be achieved. Their groundbreaking study revealed that dairy cows can develop immunity after initial exposure suggesting a vaccine would be highly effective in managing H5N1 outbreaks.
Bryce Warner, a Research Scientist with VIDO and the co-lead researcher with the project, but the idea for the project began before he joined VIDO in June 2024.
He said that VIDO always could work on this kind of research so it made sense to pursue it.
"They were getting that going and then as that was taking off, that's when the dairy cattle outbreak was identified,” he said. “It was just an obvious point for VIDO to go (for) because we have the capacity.”
More than 800 U.S. dairy cattle herds have been affected by H5N1, with the virus causing severe udder infections (mastitis) and significant drops in milk production. This spillover into cattle has raised alarm in both the agriculture sector and the global health community. Historically, cattle were considered resistant to influenza A viruses, but this discovery challenges that belief.
Leveraging VIDO’s team of expert scientists and containment Level 3 Agriculture (CL3-Ag) facility – one of only a few in the world equipped for such research and the capacity to hold large animals—was another key according to Warner.
Warner worked with Dr. Yan Zhao, an expert in influenza, and Dr. Antonio Facciuolo, the co-lead researcher. VIDO’s team mimicked natural infection by introducing the virus into the hindquarters of cows’ udders, similar to how contaminated milking equipment might spread the virus. The cows experienced mastitis, reduced milk production, and viral shedding in milk—all signs seen in infected U.S. dairy herds.
"There's only a few places in the world that can do that,” Warner explained. “Until then, it was really a matter of figuring out the logistics at that point, and, yes, we have the capacity to do it. It makes sense because we're one of only a few facilities that can do it.”
He said that the team of veterinarians were able to bring in dairy cattle and look after their welfare as the study was conducted.
Next, they created an infection model. Other groups in Germany and the United States were also working on similar studies so the USask team had to find a unique angle.
"We have discovered a few interesting things, but what still isn't fully known is what kind of protection is seen when dairy cattle are infected. That was an area that we were interested in,” he said.
But the breakthrough came when the same cows were re-exposed to the virus in the previously unaffected forequarters of their udders. This time, there were no signs of disease. Milk production remained steady, and the virus was undetectable.
They brought the dairy cattle in for the study and an initial infection and saw similar results to the other studies.
“That was reassuring to us,” Warner said. “Then we wanted to take that a step further and look at after the cows have recovered and the disease has gone. If we infect them again are they going to be protected and if they suffer from disease again, what happens there?
“That's the unique thing about our research. We were the first to show that initial infection confers protection against secondary exposure. That's really the focus of what came out from our lab.”
Warner said the next steps as suggested by the research is that the cattle should be protected by the vaccine.
"I think another step is confirming that with a vaccine and making sure that our findings hold true in that scenario because that's not always the case. Sometimes there's differences between infection and vaccination,” he explained.
The presence of H5N1 in dairy cattle introduces a new host for the virus, raising concerns about viral evolution.
"When a virus finds a new host, it’s an opportunity for mutation,” Zhou said in a press release. “Cattle could be a mixing pot for new strains, some of which might pose a greater threat to humans."
The ability of cows to develop immunity following exposure to H5N1 is a potential innovation for outbreak management. This finding suggests that vaccination could effectively induce immunity, preventing infection and reducing the impact of this disease on milk production, udder health and premature culling.
Understanding this immune response opens avenues for developing targeted interventions to protect herds. While human cases linked to infected dairy herds are rare, at least 40 have been reported. Routes of transmission are still being studied, with airborne, surface contact, and direct contact exposure all possible pathways.
Warner said that as the study continues, the logistics of housing dairy cattle may mean a change in what animals are studied.
“We were looking toward an alternative model (where) we're looking at infection in goats, how they're impacted, and how that impacts the mammary gland, and using that as a surrogate model because we can do a little bit more in terms of animal numbers and they're a little easier to work with,” Warner explained.
He added that the biggest part of the next step is the vaccine part because it can impact industry.
"I think the vaccine component is the next bigger step because that's something that is going to have consideration for the dairy industry in Canada and elsewhere, and for the producers and making sure that they can protect their herd,” he said.
According to VIDO, the discovery highlights the importance of a One Health approach—integrating human, animal, and environmental health—to tackle infectious diseases that cross-species
“VIDO is one of the few institutions worldwide capable of conducting this type of research, highlighting the critical link between human and animal health,” Dr. Volker Gerdts, Director and CEO at VIDO said in a release. “By understanding how H5N1 behaves in cows, we are better equipped to protect herds, safeguard food supplies, and reduce the risk of future pandemics.
