Potential pandemic risk of circulating swine H1N2 influenza viruses

Authors: LE SAGE, VALERIE - University Of Pittsburgh; ROCKEY, NICOLE - University Of Pittsburgh; FRENCH, ANDREA - University Of Pittsburgh; MCBRIDE, RYAN - Scripps Institute; MCCARTHY, KEVIN - University Of Pittsburgh; RIGATTI, LORA - University Of Pittsburgh; SHEPHARD, MEREDITH - Emory University; JONES, JENNY - University Of Pittsburgh; WALTER, SYDNEY - University Of Pittsburgh; DOYLE, JOSHUA - University Of Pittsburgh; XU, LINGQING - University Of Pittsburgh; BARBEAU, DOMINIQUE - University Of Pittsburgh; WANG, SHENGYANG - Scripps Institute; FRIZZELL, SHEILA - University Of Pittsburgh; MYERBURG, MICHAEL - University Of Pittsburgh; PAULSON, JAMES - Scripps Institute; MCELROY, ANITA - University Of Pittsburgh; Anderson, Tavis; Baker, Amy; LAKDAWALA, SEEMA - University Of Pittsburgh

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2024
Publication Date: 6/13/2024
Citation: Le Sage, V., Rockey, N.C., French, A.J., McBride, R., McCarthy, K.R., Rigatti, L.H., Shephard, M.J., Jones, J.E., Walter, S.G., Doyle, J.D., Xu, L., Barbeau, D.J., Wang, S., Frizzell, S.A., Myerburg, M.M., Paulson, J.C., McElroy, A.K., Anderson, T.K., Baker, A.L., Lakdawala, S.S. 2024. Potential pandemic risk of circulating swine H1N2 influenza viruses. Nature. https://doi.org/10.1038/s41467-024-49117-z.
DOI: https://doi.org/10.1038/s41467-024-49117-z

Interpretive Summary: Influenza A viruses (IAV) are endemic in both humans and pigs and these viruses readily move between hosts. This interspecies transmission increases viral diversity and has great impact on viral ecology in both hosts. Swine origin IAV have the potential to initiate human pandemics and are of great importance to pandemic preparation efforts. Because of this, we developed a decision chart to assess the risk of swine IAV to the human population. Two swine H1 IAV strains were compared to assess human population immunity, infection of human respiratory cells, and infection and transmission in ferrets with and without immunity to human seasonal IAV. Taken together, these results indicate that the swine H1N2 strain had a relatively higher pandemic potential than the swine H1N1, but may have a moderate level of impact to the human population since there was reduced replication and transmission in animals with prior immunity to human seasonal H1N1 viruses. The decision tree and risk assessment methods add to pandemic preparedness efforts by identifying swine strains of higher priority for further monitoring and human vaccine development.

Technical Abstract: Swine influenza viruses have considerable genetic diversity and continue to pose a large pandemic threat to humans. They were the source of the most recent influenza pandemic, and since 2010, novel swine viruses have spilled over into humans more than 400 times in the United States. Although these zoonotic infections generally result in mild illness with limited onward human transmission, the sustained transmission of an emerging influenza virus between individuals due to lack of population level immunity is of great concern. Compiling over a decade of research on pandemic threat assessment, we established a pipeline to characterize and triage influenza viruses for their pandemic risk. Using this flow chart, we examined the pandemic potential of two swine origin viruses. Our analysis revealed that current human sera have no cross-reactive neutralizing antibodies against an a-H1 lineage strain but does against a prevalent a-H1 lineage strain. Swine H1N2 virus from the a-H1 lineage (a-swH1N2) replicated efficiently in human airway cultures and exhibited phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, a-swH1N2 was capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity after a 2-day exposure. Ferrets with H1N1pdm09 pre-existing immunity had reduced a-swH1N2 viral shedding from the upper respiratory tract and cleared the infection faster. Despite this, H1N1pdm09-immune ferrets that became infected via the air could still onward transmit a-swH1N2 with an efficiency of 50%. Taken together, these results indicate that this a-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness in animals with prior immunity to human seasonal H1N1 viruses.