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Antigenic characterization and pandemic risk assessment of North American H1 influenza A viruses circulating in swine

Analysis and files for Venkatesh et al. (swine IAV H1 zoonotic risk)

Divya Venkatesh, Tavis K. Anderson, J. Brian Kimble, Jennifer Chang, Sara Lopes, Carine K. Souza, Andrew Pekosz, Kathryn Shaw-Saliba, Richard E. Rothman, Kuan-Fu Chen, Nicola S. Lewis, Amy L. Vincent Baker. Antigenic characterization and pandemic risk assessment of North American H1 influenza A viruses circulating in swine.bioRxiv 2022.05.04.490709; doi: https://doi.org/10.1101/2022.05.04.490709

Abstract

The first pandemic of the 21st century was caused by an H1N1 influenza A virus (IAV) introduced from pigs into humans, highlighting the importance of swine as reservoirs for pandemic viruses. Two major lineages of swine H1 circulate in North America: the 1A classical swine (including the 2009 pandemic H1N1) lineage and 1B human seasonal-like lineage. Here, we investigated the evolution of these H1 IAV lineages in North American swine and their potential pandemic risk. We assessed the antigenic distance between the HA of representative swine H1 and human seasonal H1 vaccine strains (1978-2015) in hemagglutination inhibition (HI) assays using a panel of monovalent anti-sera raised in pigs. Antigenic cross-reactivity varied by strain but was associated with genetic distance. Generally, swine 1A lineage viruses that seeded the 2009 H1 pandemic were antigenically most similar to H1 pandemic vaccine strains, with the exception of a clade within the genetic clade 1A.1.1.3 that had a two-amino acid deletion mutation near the receptor-binding site. The swine 1B lineage strains, which arose from previously circulating (pre-2009 pandemic) human seasonal viruses, were typically more antigenically similar to pre-2009 human seasonal H1 vaccine viruses. Human population immunity as a surrogate for pandemic risk was measured by cross-reactivity in HI assays to representative swine H1 strains. There was a broad range of titers against each swine strain, and this was not associated with age or sex, or location. However, there was almost no cross-reactivity in human sera to the 1A.1.1.3 and 1B.2.1 genetic clades of swine viruses. Notably, among selected strains, the 1A.1.1.3 and 1B.2.1 clades were also the most antigenically distant from all human vaccine strains. Our data demonstrate that antigenic distances of representative swine strains from human vaccine strains represent an efficient way to evaluate swine IAV for zoonotic potential.