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

Authors: VENKATESH, DIVYA - Royal Veterinary College; Anderson, Tavis; KIMBLE, BRIAN - Oak Ridge Institute For Science And Education (ORISE); CHANG, JENNIFER - Oak Ridge Institute For Science And Education (ORISE); LOPES, SARA - Royal Veterinary College; SOUZA, CARINE - Oak Ridge Institute For Science And Education (ORISE); PEKOSZ, ANDREW - Johns Hopkins University; SHAW-SALIBA, KATHRYN - Johns Hopkins University; ROTHMAN, RICHARD - Johns Hopkins University; CHEN, KUAN-FU - Chang Gung Memorial Hospital; LEWIS, NICOLA - Royal Veterinary College; Baker, Amy

Submitted to: Microbiology Spectrum
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2022
Publication Date: 12/21/2022
Citation: Venkatesh, D., Anderson, T.K., Chang, J., Lopes, S., Kimble, B., Souza, C.K., Pekosz, A., Rothman, R.E., Chen, K., Baker, A.L., Lewis, N.S. 2022. Antigenic characterization and pandemic risk assessment of North American H1 influenza A viruses circulating in swine. Microbiology Spectrum. 10(6). Article e01781-22. https://doi.org/10.1128/spectrum.01781-22.
DOI: https://doi.org/10.1128/spectrum.01781-22

Interpretive Summary: Human H1 influenza A viruses (IAV) spread to pigs in North America associated with the 1918 pandemic and more recently in the 2000s. These cross-species events led to sustained circulation of two major groups of H1 viruses in swine and increased IAV diversity in pig populations. The evolution in swine of H1 IAV led to a reduced similarity with human seasonal H1 and the vaccine strains used to protect human populations. We quantified the genetic diversity of H1 in swine, selected representative viruses, and measured the diversity of antigenic phenotypes cocirculating in North American pigs. We demonstrated that North American swine H1 lineages were significantly different from historical and recent human vaccine strains and this antigenic dissimilarity increased over time as the viruses evolved in swine. Additionally, pandemic preparedness vaccine strains developed for public health also demonstrated a loss in similarity with contemporary swine strains. Lastly, post-exposure and post-vaccination human sera revealed a diversity of responses to swine IAV, including two groups of viruses where there was little to no immunity to the swine H1. Genomic surveillance and analysis paired with antigenic assessments of swine H1 IAV identified gaps in current pandemic preparedness efforts and this information can help guide candidate vaccine development for public health.

Technical 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.