A new frontier in avian flu research: Dairy cows build a natural immunity to H5N1 after initial infection

Jan 7, 2025

When highly pathogenic avian influenza (HPAI) H5N1 was detected in U.S. dairy cattle in March 2024, it sparked a wave of urgent research. Scientists at the 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.

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.

Key Findings from the Research

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 – 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.

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.

"Our findings demonstrate that natural infection can induce immunity that protects against reinfection in other parts of the udder," said Dr. Antonio Facciuolo, one of the study’s co-lead researchers. "This discovery is a great indication that a vaccine will be effective which has significant implications for how we approach HPAI outbreaks in dairy cattle."

Why This Discovery Matters

The presence of H5N1 in dairy cattle introduces a new host for the virus, raising concerns about viral evolution. As Dr. Yan Zhou, co-lead researcher for this study, notes, "When a virus finds a new host, it’s an opportunity for mutation. 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 game-changer 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.

What’s Next?

VIDO’s research is ongoing, focusing on identifying how natural immunity is providing protection in the mammary gland (udders) which could lead to vaccine or other preventative measures in dairy herds. VIDO is also actively engaged with the Research Alliance for Veterinary Science and Biodefense BSL-3(RAV3N) – to support response efforts to this emerging infectious disease.  VIDO is the only non-American member.

"If we can understand what’s driving this immune response, we could transform how we protect animals and people from H5N1," said Dr. Bryce Warner, co-lead researcher for this study.

The discovery highlights the importance of a One Health approach—integrating human, animal, and environmental health—to tackle infectious diseases that cross species. The full research paper is available for those interested in the study’s methods and implications.

“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, added. “By understanding how H5N1 behaves in cows, we are better equipped to protect herds, safeguard food supplies, and reduce the risk of future pandemics.”