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Preexisting immunity to the 2009 pandemic H1N1 virus reduces susceptibility to H5N1 infection and disease in ferrets.

Katherine H Restori1,2 Veronika Weaver1,2 Devanshi R Patel1 Grace A Merrbach3 Kayla M Septer1 Cassandra J Field1,2,4 Michael J Bernabe1 Ethan M Kronthal1 Allen Minns4,5 Scott E Lindner4,5 Seema S Lakdawala6 Valerie Le Sage3,7 Troy C Sutton1,2,4
Affiliations 7 institutions
  1. Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802, USA.
  2. Emory Center of Excellence of Influenza Research and Response (CEIRR), University Park, PA 16802, USA.
  3. Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  4. Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  5. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
  6. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
  7. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
PMID40700518 DOI10.1126/scitranslmed.adw4856 Year2025 Journal Science translational medicine Sci Transl Med Languageeng Statusppublish

Abstract

Zoonotic infections with emerging influenza viruses occur in the context of population-wide immunity to seasonal strains. Because of the worldwide spread of highly pathogenic clade 2.3.4.4b H5N1 influenza viruses in wild birds, there have been numerous spillover events into mammals. This includes a recent spillover into dairy cows that started an ongoing outbreak across the United States. Human infections with avian and bovine origin H5N1 influenza viruses have been documented, raising concern that these viruses may cause a pandemic. Therefore, using a ferret model, we evaluated the impact of preexisting, infection-elicited immunity on susceptibility to H5N1 infection and on severity of disease. Preexisting immunity to the 2009 pandemic H1N1 influenza virus prevented severe H5N1 disease and reduced susceptibility to infection through direct contact with an infected donor ferret. These studies demonstrate that preexisting immunity to influenza viruses, especially the 2009 pandemic H1N1 virus, is a barrier to infection and disease caused by clade 2.3.4.4b H5N1 viruses.

Ferrets 79 Influenza A Virus, H1N1 Subtype 74 Influenza A Virus, H5N1 Subtype 300 Influenza, Human 286 Orthomyxoviridae Infections 228 Pandemics 108 Animals 1948 Disease Susceptibility 21 Humans 1440

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