Colorized transmission electron micrograph of Avian influenza A H5N1 viruses. Credit score: Public Area
The fatality charge for H5N1 extremely pathogenic avian influenza in people has traditionally been excessive, with greater than half of individuals dying. Why, then, is the present H5N1 chicken flu outbreak—which has prompted large die-offs in wild birds, farmed poultry and even wild mammals—inflicting principally delicate signs within the individuals it has contaminated?
New analysis, led by scientists at Penn State and the College of Pittsburgh and revealed within the journal Science Translational Medication, signifies that immunity to a seasonal influenza virus often called pandemic H1N1 that started circulating in 2009, gives safety from extreme sickness from H5N1 in a laboratory animal mannequin.
“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” stated lead writer Troy Sutton, affiliate professor of veterinary and biomedical sciences at Penn State.
“Our findings suggest that this immunity is protective against the more recent H5N1 strain and may explain why we’re seeing fewer cases and less severe disease than we would expect.”
H5N1 viruses from clade 2.3.4.4b emerged in 2020 and have been carried world wide by wild migratory birds, the place they’ve since contaminated farmed poultry, wild mammals and, most lately, dairy cattle.
As of June 2025, 70 human instances of H5N1 have been confirmed in america with one dying. A lot of the people have been uncovered to dairy cows or poultry and exhibited delicate signs of conjunctivitis, fever and cough, amongst others.
In contrast, earlier human infections with H5N1 resulted in much more extreme signs, equivalent to seizures and respiratory failure, and a few contaminated individuals died from the an infection or associated problems.
“We wanted to know why H5N1 2.3.4.4b was not causing severe outcomes so we investigated whether pre-existing immunity to seasonal influenza could be providing protection,” stated Katherine Restori, assistant analysis professor of veterinary and biomedical sciences, Penn State.
Restori defined that this analysis was performed in ferrets, that are well known as among the best animal fashions for learning influenza virus infections.
To conduct their examine, Sutton and his colleagues, together with Valerie LeSage, analysis assistant professor, College of Pittsburgh, who co-led the analysis, studied ferrets with immunity to 3 widespread forms of seasonal flu: Influenza B, H1N1 and H3N2. Additionally they studied a management group of ferrets that had no immunity to flu.
Ninety days after infecting the ferrets with these widespread seasonal flu viruses, the staff confirmed immunity by testing the animals’ blood for antibodies.
Subsequent, the staff uncovered the ferrets via an inoculation within the nostril to a model of the H5N1 virus that prompted an outbreak on mink farms in Spain in 2022.
They discovered that every one the ferrets with out immunity to the seasonal flu viruses, in addition to these with immunity to Influenza B, turned sick, misplaced weight and reached a humane endpoint. The H3N2-immune ferrets misplaced 10% of their physique weight however all survived.
In distinction, the ferrets with immunity to H1N1 didn’t lose any weight and all survived.
Subsequent, the staff studied the potential protecting results of the identical three seasonal influenza viruses in opposition to the newer H5N1 virus that has been circulating in dairy cattle.
This time, as a substitute of inoculating the ferrets with H5N1 within the nostril, the staff uncovered ferrets with immunity to H1N1, H3N2, or with out immunity to a seasonal virus, to ferrets already contaminated with an H5N1 virus from dairy cows.
Sutton stated by analyzing publicity to H5N1-infected ferrets, the staff may assess the transmissibility of the virus along with the results of pre-existing immunity.
The researchers discovered that upon publicity to ferrets with dairy cow H5N1 infections, ferrets with none influenza immunity quickly developed extreme and deadly illness.
When uncovered to H5N1-infected ferrets, all of the ferrets with pre-existing immunity to H3N2 turned contaminated and replicating H5N1 virus was detected of their noses. These ferrets misplaced weight and half of them reached a humane endpoint.
In distinction, solely half of the ferrets beforehand contaminated with the 2009 H1N1 virus turned contaminated, and the contaminated animals have been protected in opposition to illness and had very low ranges of viral replication within the nostril.
“These findings demonstrate 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,” Sutton stated.
“This study provides a potential explanation for the mostly mild disease we are seeing in humans, as humans already have immunity to H1N1.” Nevertheless, Sutton famous, because the H5N1 virus continues to flow into in animals, it has alternatives to evolve to grow to be extra harmful.
Experiments utilizing the mink H5N1 and dairy cattle H5N1 viruses have been carried out in Penn State’s biosafety degree 3 Eva J. Pell Laboratory for Superior Organic Analysis. This facility is permitted by the Facilities for Illness Management and Prevention and United States Division of Agriculture for work with extremely pathogenic avian influenza. All experiments have been carried out in compliance with all native, state and federal guidelines and rules.
Extra info:
Katherine Restori et al, Preexisting immunity to the 2009 pandemic H1N1 virus reduces susceptibility to H5N1 an infection and illness in ferrets, Science Translational Medication (2025). DOI: 10.1126/scitranslmed.adw4856. www.science.org/doi/10.1126/scitranslmed.adw4856
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Immunity to seasonal flu protects in opposition to extreme sickness from chicken flu in ferrets, analysis reveals (2025, July 23)
retrieved 23 July 2025
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