Understanding H5N1: UW Vet Med scientists working to protect dairy cows, prevent pandemics

by Jack Kelly

Scientists at the UW School of Veterinary Medicine (SVM) are on the front lines of understanding H5N1 avian flu and developing tools to fight the virus.

Their work comes at a critical juncture, with the virus continuing to fuel outbreaks in poultry and cattle on farms in the U.S., according to the Centers for Disease Control and Prevention. Several human cases affecting poultry and dairy workers have also been reported.

Clara Cole (BS’17 DVM’21), a second-year PhD student in the Comparative Biomedical Sciences Graduate Program, is investigating the impacts of H5N1 on mammals, with a particular focus on how the virus affects the mammary glands. Her DVM coursework at the SVM, including a class taught by Marulasiddappa Suresh (Department of Pathobiological Sciences), inspired her to pursue a PhD in immunology. Suresh, John E. Butler Professor in Comparative and Mucosal Immunology, also serves as the SVM’s associate dean for research and graduate education. Cole now works in his lab.

“I like solving puzzles, solving mysteries,” Cole says. “I like getting my hands dirty. And my current work brings all of those things together.”

The puzzle she’s trying to crack now has serious implications for both the economy and public health. The spread of H5N1 has contributed to increased prices at grocery stores for things like eggs, Cole says, because infected flocks have been culled to limit the spread of the virus.

H5N1 threatens the dairy industry, too, because the virus can cause mastitis (inflammation of the mammary glands) in dairy cattle which results in reduced milk production and lower quality milk. And there are public health concerns: If the virus continues to spread among different species — it has been detected in sheep, pigs, seals, and even polar bears — it is more likely to undergo gene segment reassortment or mutate, Cole says. While the virus in its current form struggles to infect humans, a future reassortment or mutation could be the source of the next pandemic.

H5N1 appears to spread among dairy cows not primarily through the upper respiratory tract, the usual route for flu viruses, but through the udders after cows encounter contaminated milking equipment.

That presents two challenges to Cole, who, in collaboration with Suresh and Yoshihiro Kawaoka (Department of Pathobiological Sciences), is working to develop an effective vaccine to protect cattle against H5N1 and similar viruses.

Not only do the animals need to be protected against respiratory transmission, but they also need safeguards against infection via their mammary glands — something that’s never been done before, Suresh says. This is especially important because the animals have considerably worse symptoms when they are infected via their udders.

The scientists are conducting immunogenicity studies, which test to see whether a vaccine candidate stimulates an immune response. Early results have been remarkably promising, says Suresh, who also serves as the school’s associate dean for research and graduate training.

This image shows the step-by-step process of “gating” (or selecting) specific groups of cells from a larger sample using a flow cytometer machine. Think of it like using a series of digital filters to isolate certain cells, one filter at a time. The goal of Cole’s work is to isolate and study certain T cells — white blood cells essential for immune response — related to vaccine-induced immunity.

The researchers have been able to elicit antibodies in both the blood and milk of cows that have received the vaccine. Antibodies help neutralize the virus before it can infect cells. They have also detected a T-cell response in the cows’ blood. T-cells target and kill infected cells.

Cole, whose work is supported by a National Institutes of Health T32 training grant, is now studying whether the new vaccines can stand up to the virus in mice. Using a carefully regimented hormone series, she is able to make the mice lactate without being pregnant — simulating a dairy cow at a much smaller scale. The milk produced by the mice is collected each day and certain tissues are tested after the mice have encountered the virus.

Her colleagues are still examining the effectiveness of vaccine candidates against the virus and hope to have a clearer picture of their efficacy in the coming months. Science takes time, Cole notes, and she remains committed to doing work that helps improve the health of both animals and humans.

“On the off chance the virus does mutate and humans become more susceptible to it, I want to help prevent another pandemic,” she says. “I want to do whatever I can to help save both animal and human lives.”


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