The fatality rate for H5N1 highly pathogenic avian influenza in humans has historically been high, with more than half of people dying. However, the current H5N1 bird flu outbreak is causing mostly mild symptoms in the people it has infected. New research, led by scientists at Penn State and the University of Pittsburgh, suggests that immunity to a seasonal influenza virus known as pandemic H1N1 that began circulating in 2009 provides protection from severe illness from H5N1 in a laboratory animal model.
Lead author Troy Sutton, associate professor of veterinary and biomedical sciences at Penn State, explained that every person has been exposed to H1N1 as the virus caused a pandemic in 2009 and is now the predominant circulating influenza strain in one out of every three to four years. The findings of the study indicate that this immunity is protective against the more recent H5N1 strain and may explain why there are fewer cases and less severe disease than expected.
H5N1 viruses from clade 2.3.4.4b emerged in 2020 and have since infected farmed poultry, wild mammals, and even dairy cattle. As of June 2025, 70 human cases of H5N1 have been confirmed in the United States with one death, mostly exhibiting mild symptoms such as conjunctivitis, fever, and cough.
Previous human infections with H5N1 resulted in severe symptoms, including seizures and respiratory failure, leading to deaths. The research conducted in ferrets, a widely recognized animal model for studying influenza virus infections, showed that pre-existing immunity to the 2009 H1N1 virus or H3N2 virus reduces the severity of H5N1 disease, with H1N1 providing even greater protection than H3N2.
The study demonstrated that ferrets with immunity to H1N1 did not lose weight and all survived when exposed to H5N1, while ferrets without immunity or with immunity to Influenza B became sick and lost weight. The findings suggest that pre-existing immunity to seasonal influenza viruses can provide protection against severe illness from H5N1.
However, the researchers noted that as the H5N1 virus continues to circulate in animals, it has the potential to evolve and become more dangerous. The study was conducted in compliance with all local, state, and federal rules and regulations, using the Penn State biosafety level 3 facility for research with highly pathogenic avian influenza.
In conclusion, the research provides insights into how pre-existing immunity to seasonal flu viruses can protect against severe illness from bird flu in ferrets. This new understanding could help inform future strategies for managing and preventing outbreaks of avian influenza in both animals and humans.
