Since 2022, Minnesota poultry producers have faced devastating losses from an aggressive strain of H5N1 avian influenza, known as 2.3.4.4b clade, first transmitted by migratory birds from Europe. Millions of birds have been affected in all fifty states across the U.S., and many farms devastated. But few studies have probed how this virus is evolving and how the change of the virus impacts its transmission and infection in poultry.

Now, with $650,000 in new funding from the U.S. Department of Agriculture National Institute of Food and Agriculture (USDA-NIFA), researchers at the University of Minnesota College of Veterinary Medicine (CVM) are stepping in to close that gap. Led by Zheng Xing, professor in the Department of Veterinary and Biomedical Sciences, the project will investigate how recent strains of the highly pathogenic H5N1 behave in poultry and test a new vaccine strategy to help prevent future outbreaks.

A moving target

The H5N1 virus circulating today is not the same one that first appeared in North America ten years ago. It belongs to a genetic branch known as 2.3.4.4b, and it continues to evolve by mixing with other flu viruses carried in wild birds in a process called reassortment. That results in new versions of the virus—such as B3.13, which emerged early 2024 and eventually spread to dairy cows in March 2025. Each variant may have different characteristics that impact how easily it can spread, how sick it might make birds and other animals, and how difficult it is to control.

Xing and his collaborators are analyzing virus strains isolated from poultry and cattle farms, in order to identify the virus’s evolutionary stages and understand how this evolution affects its transmission and virulence in birds.  They are focusing on three different strains that have emerged over the last three years:

• A 2022 version from a Minnesota turkey, showing early genetic mixing
• A 2023 version that still closely matches the original virus from Europe
• A 2024 version linked to outbreaks in both dairy cattle and poultry initially in Texas, with signs of more recent genetic changes

Science with an eye toward solutions

“We are interested in knowing how the H5N1 viruses vary in their virulence and transmission in chickens and turkeys,” Xing explains. “We will collect data on virus shedding, death rates, and direct and aerosol-transmission efficiency. We have some information from poultry farms affected by the H5N1 outbreaks, but there have been no studies designed to analyze and compare the parameters these viruses exhibit in poultry.” 

The research team is also testing a new type of vaccine designed to target the most recent version of the virus now spreading in poultry. Currently, four vaccines are licensed by the USDA for use in U.S. poultry for avian influenza, but none are approved for the new, more virulent 2.3.4.4b viruses.

The vaccine that Xing’s team proposes to develop uses microRNA-based technology to weaken the virus in a precise, controlled way. If successful, it could offer a safer and more targeted approach to protecting flocks during future outbreaks.

Protecting birds, producers, and the food supply

Minnesota is the top turkey-producing state in the nation and sits along the Central Flyway, a major migration route for wild birds. Those two factors make the state particularly vulnerable to avian flu.

“The outcome of the project could provide key information about how the reassortment or other mutation affects the 2.3.4.4b H5N1 viruses in their efficiency to be spread to chickens and turkeys and their mortality in poultry," Xing suggests. “This will lead to more in-depth research to identify viral genomic elements that contribute to viral virulence and transmission.”

Beyond its basic scientific value, the research aims to deliver real-world solutions. By understanding how this evolving virus works—and how to defend against it—CVM researchers are helping protect Minnesota’s poultry farms, maintain a secure food supply, and support one of the state’s most vital agricultural industries.