Potential pandemic risk of circulating swine H1N2 influenza viruses

• Published in: Nature communications Vol. 15; no. 1; pp. 5025 - 13
• Main Authors: Le Sage, Valerie, Rockey, Nicole C., French, Andrea J., McBride, Ryan, McCarthy, Kevin R., Rigatti, Lora H., Shephard, Meredith J., Jones, Jennifer E., Walter, Sydney G., Doyle, Joshua D., Xu, Lingqing, Barbeau, Dominique J., Wang, Shengyang, Frizzell, Sheila A., Myerburg, Michael M., Paulson, James C., McElroy, Anita K., Anderson, Tavis K., Vincent Baker, Amy L., Lakdawala, Seema S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-06-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 45; 631/326/1762; 631/326/596/1578; 64; 692/420/254; Adult; Animal pathology; Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Female; Ferrets - virology; Genetic diversity; Humanities and Social Sciences; Humans; Immunity; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A Virus, H1N2 Subtype - genetics; Influenza A Virus, H1N2 Subtype - immunology; Influenza, Human - blood; Influenza, Human - epidemiology; Influenza, Human - immunology; Influenza, Human - transmission; Influenza, Human - virology; Male; multidisciplinary; Mustela; Orthomyxoviridae; Orthomyxoviridae Infections - blood; Orthomyxoviridae Infections - epidemiology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - virology; Pandemics; Risk; Science; Science (multidisciplinary); Swine; Swine Diseases - blood; Swine Diseases - epidemiology; Swine Diseases - immunology; Swine Diseases - transmission; Swine Diseases - virology; Swine influenza; Virus Replication; Virus Shedding; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49117-z

Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity.
Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.