The fatality fee 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 brought on large die-offs in wild birds, farmed poultry and even wild mammals—inflicting principally gentle signs within the folks it has contaminated?
New analysis, led by scientists at Penn State and the College of Pittsburgh and printed within the journal Science Translational Drugs, signifies that immunity to a seasonal influenza virus generally known as pandemic H1N1 that started circulating in 2009, gives safety from extreme sickness from H5N1 in a laboratory animal mannequin.
“Each individual has been uncovered to H1N1 because the virus brought on a pandemic in 2009 and is now the predominant circulating influenza pressure in a single out of each three to 4 years” stated lead writer Troy Sutton, affiliate professor of veterinary and biomedical sciences at Penn State.
“Our findings counsel that this immunity is protecting in opposition to the newer H5N1 pressure and should clarify why we’re seeing fewer circumstances and fewer extreme illness than we’d anticipate.”
H5N1 viruses from clade 2.3.4.4b emerged in 2020 and had 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 circumstances of H5N1 have been confirmed in the US with one demise. A lot of the people had been uncovered to dairy cows or poultry and exhibited gentle signs of conjunctivitis, fever and cough, amongst others.
In contrast, earlier human infections with H5N1 resulted in much more extreme signs, corresponding to seizures and respiratory failure, and a few contaminated folks died from the an infection or associated problems.
“We wished to know why H5N1 2.3.4.4b was not inflicting extreme outcomes so we investigated whether or not pre-existing immunity to seasonal influenza might be offering safety,” stated Katherine Restori, assistant analysis professor of veterinary and biomedical sciences, Penn State.
Restori defined that this analysis was performed in ferrets, that are widely known as among the finest animal fashions for learning influenza virus infections.
To conduct their research, 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. In addition 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 group confirmed immunity by testing the animals’ blood for antibodies.
Subsequent, the group uncovered the ferrets by way of an inoculation within the nostril to a model of the H5N1 virus that brought on 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, grew to become 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 group 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 an alternative of inoculating the ferrets with H5N1 within the nostril, the group 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 inspecting publicity to H5N1-infected ferrets, the group may assess the transmissibility of the virus along with the consequences 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 grew to become 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 grew to become contaminated, and the contaminated animals had been protected in opposition to illness and had very low ranges of viral replication within the nostril.
“These findings reveal that pre-existing immunity to the 2009 H1N1 virus or H3N2 virus reduces the severity of H5N1 illness, with H1N1 offering even larger safety than H3N2,” Sutton stated.
“This research gives a possible clarification for the principally gentle illness we’re seeing in people, as people have already got immunity to H1N1.” Nonetheless, Sutton famous, because the H5N1 virus continues to flow into in animals, it has alternatives to evolve to change into extra harmful.
Experiments utilizing the mink H5N1 and dairy cattle H5N1 viruses had been carried out in Penn State’s biosafety stage 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 had been carried out in compliance with all native, state and federal guidelines and laws.
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 Drugs (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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