New research from the University of Pittsburgh School of Medicine and Emory University suggests that prior exposure to seasonal H1N1 influenza may help protect against severe disease and death from H5N1 bird flu.
The study, published in Emerging Infectious Diseases, found that pre-existing immunity shaped the severity of H5N1 infections in a ferret model, offering insights into why most human cases in the U.S. have not been fatal despite the virus’s deadly nature in animals.
Pre-Existing Immunity Reduces Severity of Infection in H5N1 Bird Flu
The ongoing H5N1 outbreak has spread among wild birds, poultry, and dairy cattle since March 2024, raising concerns about potential human transmission. However, despite the virus’s high fatality rate in animals, it has not caused widespread severe disease in humans.
To investigate why, researchers studied ferrets, which develop flu symptoms similar to humans, including fever, sneezing, and respiratory issues.
- Ferrets previously exposed to H1N1 survived an H5N1 infection and showed milder symptoms than those without prior immunity.
- With no prior flu exposure, ferrets experienced severe illness, more significant weight loss, and signs of systemic infection, with the virus spreading beyond the respiratory system to the heart, liver, and spleen.
- Despite both groups sustaining lung tissue damage, the H1N1-immune ferrets cleared the virus from their nasal passages more quickly, limiting the infection to the respiratory tract.
“All human flu pandemics emerge in the context of pre-existing immunity,” said Dr. Valerie Le Sage, lead author and research assistant professor at the University of Pittsburgh. “Our model isn’t perfect because the human immune response is complicated, but using ferrets as surrogates, it’s important to consider prior immunity.”
Why H1N1 Exposure Helps—But Vaccines May Not
The mechanism behind this cross-protection remains unclear. Researchers found that antibodies created in response to H1N1 do not inactivate H5N1, meaning that protection is not due to direct immunity against the virus. As a result, seasonal flu vaccines targeting H1N1 are unlikely to prevent severe H5N1 disease.
“The study findings suggest that prior H1N1 infection won’t stop someone from getting H5N1, but it can make the illness less severe,” said Dr. Seema Lakdawala, senior author and professor at Emory University’s School of Medicine. H5N1 Bird Flu.
However, Lakdawala cautioned that certain groups—including young children, immunocompromised individuals, and people with underlying health conditions—could still experience severe illness.
Implications for Pandemic Preparedness
The World Health Organization currently assesses the risk of H5N1 to the general po. Still, theas low, but the virus’s spread in dairy cattle and other mammals raises concerns about future mutations that could make it more transmissible among humans.
“Further study into whether vaccination can provide the same level of protection is still needed,” Lakdawala said. “Immune responses generated by infection are different from those generated by vaccination.”
While annual flu vaccinations remain recommended to protect against seasonal influenza, there is no recommendation for an H5N1 vaccine. This study highlights the importance of monitoring pre-existing immunity when assessing pandemic risks and preparing for future outbreaks.
Reference: Valerie Le Sage, Bailee D. Werner, Grace A. Merrbach, Sarah E. Petnuch, Aoife K. O’Connell, Holly C. Simmons, Kevin R. McCarthy, Douglas S. Reed, Louise H. Moncla, Disha Bhavsar, Florian Krammer, Nicholas A. Crossland, Anita K. McElroy, W. Paul Duprex, Seema S. Lakdawala. Influenza A(H5N1) Immune Response among Ferrets with Influenza A(H1N1)pdm09 Immunity. Emerging Infectious Diseases, 2025.
