Antigenic evolution of H3N2 influenza A viruses in swine in the United States, 2012–16

Authors: BOLTON, MARCUS - Orise Fellow; Abente, Eugenio; VENKATESH, DIVYA - University Of Cambridge; Stratton, Jered; ZELLER, MICHAEL - Iowa State University; Anderson, Tavis; LEWIS, NICOLA - University Of Cambridge; Baker, Amy

Submitted to: Influenza and Other Respiratory Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2018
Publication Date: 9/14/2018
Citation: Bolton, M.J., Abente, E.J., Venkatesh, D., Stratton, J.A., Zeller, M., Anderson, T.K., Lewis, N.S., Vincent, A.L. 2018. Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012–2016. Influenza and Other Respiratory Viruses. 13:83-90. https://doi.org/10.1111/irv.12610.
DOI: https://doi.org/10.1111/irv.12610

Interpretive Summary: Influenza A virus (IAV) is an important respiratory pathogen in swine, contributing to significant losses due to decreased rates of gain, increased antibiotic and vaccine costs, and increased death loss. IAV can be divided into three subtypes in swine, H1N1, H1N2 and H3N2, but there is extensive diversity within each of these groups that can interfere with immunity from vaccination or prior infection. Genetic characterization of contemporary hemagglutinin gene sequences from H3 IAV in swine revealed increased diversity at specific sites within the gene that are associated with antibody recognition. These specific sites in the H3 sequences were used to predict antibody recognition, viruses were characterized to test the predictions, and antigenic properties were defined based on these results. We found that there were many antigenically distinct viruses circulating in the U.S. swine population, but that sequence-based predictions of antigenic phenotype are possible. Understanding antigenic diversity in swine IAV has important implications for effective vaccine design, and the findings from this study are critical to help inform vaccine manufacturers and swine producers on how to develop and implement vaccines to reduce circulation of this important pathogen in swine.

Technical Abstract: Background: Six amino acid positions (145, 155, 156, 158, 159 and 189, referred to as the antigenic motif; H3 numbering) in the globular head region of hemagglutinin (HA1 domain) play an important role in defining the antigenic phenotype of swine Clade IV (C-IV) H3N2 IAV, containing an H3 from a late 1990s human-to-swine introduction. We hypothesized that antigenicity of a swine C-IV H3 virus could be inferred based upon the antigenic motif if it matched a previously characterized antigen with the same motif. An increasing number of C-IV H3 genes encoding antigenic motifs that had not been previously characterized were observed in the U.S. pig population between 2012-2016. Objectives: A broad panel of contemporary H3 viruses with uncharacterized antigenic motifs were selected across multiple clades within C-IV to assess the impact of HA1 genetic diversity on the antigenic phenotype. Methods: Hemagglutination inhibition (HI) assays were performed with isolates selected based on antigenic motif, tested against a panel of swine anti-sera, and visualized by antigenic cartography. Results: A previously uncharacterized motif with low but sustained circulation in the swine population demonstrated a distinct phenotype from those previously characterized. Antigenic variation increased for viruses with similar antigenic motifs, likely due to amino acid substitutions outside the motif. Conclusions: Although antigenic motifs were largely associated with antigenic distances, substantial diversity among co-circulating viruses poses a significant challenge for effective vaccine development. Continued surveillance and antigenic characterization of circulating strains is critical for improving vaccine efforts to control C-IV H3 IAV in U.S. swine.