When highly pathogenic avian influenza (HPAI) became widespread in chickens, farmers were forced to eliminate entire flocks and egg prices rose. Adding complexity to the issue was the diagnosis of HPAI in dairy cattle. Behind the scenes, researchers worked to understand and slow the spread of HPAI.

Dr. Deana Jones, center director for the U.S. National Poultry Research Center (USNPRC), outlined key aspects of the rapid response that began one year ago.

“In March of 2024, high-path avian influenza was detected in lactating dairy cows,” said Jones, who spoke recently at the USDA Ag Outlook Forum. “This spillover event (a virus overcoming barriers to establish in other species) was remarkable and the USDA-ARS immediately went to work on the problem.”

Within 24 hours of the confirmation of the virus in lactating dairy cows, scientists at the USNPRC began conducting benchtop pasteurization studies with raw cows’ milk.

“This also involved many hours in high containment, developing methods to detect the virus in fluid milk and frozen dairy products and in fermented and cultured dairy products,” said Jones. “USNPRC became a strategic partner with the FDA to conduct surveys of retail dairy products to determine the prevalence of HPAI virus in consumer dairy products.” No viable virus was detected after testing hundreds of dairy products.

To conduct studies, the USNPRC modified a high-containment ag suite, with open housing arrangements for animals, to place a pilot milk pasteurizer. In conjunction with FDA, scientists commercially pasteurized raw whole milk inoculated with HPAI and found the virus was inactivated through pasteurization.

USNPRC continues to conduct and support research to develop vaccines for both poultry and cattle. At the National Centers for Animal Health (NADC), researchers began to track the molecular characteristics and movement of the HPAI dairy isolate around the country.

The NADC also began modifying animal high-containment spaces to house lactating dairy cattle during research. “This was not a simple task due to the welfare needs of the animals, the size of the animals and the specialized training needed for staff,” said Jones. “NADC scientists were the first in the world to inoculate lactating dairy cows in high containment and observe similar clinical responses as seen in the positive herds. They also demonstrated that the virus delivered by aerosol to calves produced a mild but minimal disease.”

One important NADC study was aimed at gauging potential HPAI virus transmission between cows by milking equipment and determined immune responses of convalescent cattle. Research also focused on susceptibility to mammary gland inoculation and susceptibility of calves to oronasal exposure when fed infected milk.

The NADC is currently collaborating with commercial partners to assess the efficacy of HPAI vaccines for cattle. “The ability of the USDA-ARS high-containment laboratory to pivot and quickly respond to exotic and emerging animal diseases is a national asset,” said Jones. “The scientific experts in ARS quickly adapted to HPAI virus dairy spillover, providing essential information to stakeholders. This research was conducted while continuing other HPAI virus priority research in poultry and swine.”

Dr. Tavis Anderson, research biologist at NADC, studies viruses and has spent the last 20 years focused on the influenza A virus in pigs. “When studying a virus, we have to know about the virus, know about the animal it’s in and the environment,” he said. “We also need the ability to synthesize all of that and link it together.”

Anderson explained that influenza A viruses commonly move between species. “It’s generally people infecting pigs,” he said. “Occasionally, some bird viruses get into pigs. Sometimes the viruses in pigs get back into people – hence the swine origin pandemic of 2009.”

When avian influenza was detected in cows, scientists were able to pivot quickly because they’re accustomed to thinking about the movement of viruses among animal species. Anderson said the virus research techniques developed at NADC were immediately applicable.

“We’re looking at the genetic sequence of these viruses taken from clinically sick animals or asymptomatic animals,” he said, “and looking at patterns in the genetic sequence data to infer transmission.”

Anderson said the H5 virus that causes HPAI had been circulating primarily in migratory birds for several years. Through that circulation within North America, the virus picked up a novel combination of genes, including one gene that may be associated with changes in transmission efficiency.

It’s important to note that HPAI was a single spillover event rather than an event that occurred repeatedly. Researchers also demonstrated that asymptomatic or pre-symptomatic dairy cattle had been moved prior to being diagnosed, and that animal movement, a critical part of modern agricultural production, was responsible for virus dissemination.

After looking at genetic sequencing data, researchers determined that HPAI is still essentially an avian virus. During early research in dairy cattle, researchers found that the virus was present primarily in the mammary gland, which has two types of receptors – mammalian and avian-like. Anderson said there was no pressure for the virus to evolve to become a mammal-like virus that would make it more easily transmitted among mammals, but that aspect is still being monitored.

With genetic sequencing tools, researchers can determine the best representative of genetic diversity from all collected viruses. “We can pass that to the wet lab colleagues who initiated studies in containment labs and determine cause of infection, pathology, transmission dynamics and, ultimately, control through vaccination,” said Anderson.

Ongoing studies focus on determining which gene combinations matter and which genes drive virus evolution. One aspect of this work is filtering data to discover whether the virus is evolving in ways that will make it more difficult for a vaccine to work.

Research is also concentrated on assessing the risk of the virus moving from dairy cattle back to humans or other hosts.

by Sally Colby