Antigenic distance of swine and human seasonal H3N2 influenza A virus strains as an indication of risk to human populations

Authors: SOUZA, CARINE - Orise Fellow; ANDERSON, TAVIS K - Orise Fellow; BOLTON, MARCUS - Orise Fellow; VENKATESH, DIVYA - University Of Cambridge; LEWIS, NICOLA - University Of Cambridge; DETMER, SUSAN - University Of Saskatchewan; MENA, IGNACIO - The Icahn School Of Medicine At Mount Sinai; CULHANE, MARIE - University Of Minnesota; NELSON, MARTHA - Fogarty International Center; LARSEN, LARS E - Technical University Of Denmark; Abente, Eugenio; GARCÍA-SASTRE, ADOLFO - The Icahn School Of Medicine At Mount Sinai; Baker, Amy

Submitted to: Proceedings of Allen D Leman Swine Conference
Publication Type: Abstract Only
Publication Acceptance Date: 8/15/2018
Publication Date: 9/15/2018
Citation: Souza, C.K., Anderson, T., Bolton, M., Venkatesh, D., Lewis, N., Detmer, S.E., Mena, I., Culhane, M., Nelson, M., Larsen, L., Abente, E.J., García-Sastre, A., Vincent, A.L. 2018. Antigenic distance of swine and human seasonal H3N2 influenza A virus strains as an indication of risk to human populations [abstract]. Proceedings of Allen D Leman Swine Conference. p. none assigned.

Interpretive Summary:

Technical Abstract: Human-to-swine interspecies transmission of influenza A virus (IAV) occurs globally and contributes to an increased IAV diversity in pig populations. In the 1990s, human H3N2 spillovers into swine occurred in North America, which sustained in the pig population and genetically evolved into a stable swine cluster-IV (C-IV) lineage based on phylogenetic clustering. More recently, a 2010 human seasonal H3N2 IAV introduction was detected in U.S. swine, and is now the predominant H3N2 IAV lineage in the U.S. pig population. This lineage is referred to as H3.2010.1 to differentiate from C-IV. Both C-IV and H3.2010.1 H3N2 have been associated with variant H3N2 (H3N2v) detections and illness in humans in the USA. Additionally, independent human-to-swine H3N2 incursions were detected in Mexico (H3.1980.1) and Denmark (H3.2000.3). These events highlight the potential for re-emergence of IAV from swine back into humans. Our goal was to quantify antigenic distance between endemic H3N2 swine strains and human seasonal vaccine strains in order to identify swine strains against which the human population would lack cross-reactive HI antibodies. Hemagglutination inhibition (HI) assays were performed using a panel of monovalent anti-sera raised in pigs against human seasonal H3N2 vaccine strains from 1973 to 2014 and contemporary swine H3N2 strains from U.S., Mexico, Canada and Denmark. HI data was used to calculate antigenic distances between antigens using antigenic cartography, with 1 antigenic unit (AU) equivalent to a 2-fold loss in HI cross-reactivity and 3 AU considered significant antigenic distance. Contemporary swine H3 C-IV strains from U.S. (2.4-5.2 AU), Canada (2.6-6.4 AU) and Mexico (1.0-5.9 AU) were most antigenically related to human vaccine strains from the 1990 decade, consistent with the human-to-swine H3 spillover in North America in the mid-1990s, but with evidence of antigenic drift. However, C-IV swine strains showed substantial antigenic drift from more recent human vaccine strains, whereas swine H3N2 resulting from recent human-to-swine introductions in the USA (H3.2010.1 and H3.2010.2 lineages) and Denmark (H3.2000.3), demonstrated closer antigenic relationships to recent human vaccine strains from the 2000 and 2010 decades (0.4- 4.3AU) and increased distance to older human vaccine strains. These antigenic relationships may indicate swine strains that pose a public health risk based on the loss in cross-reactivity to human vaccine strains. Future work will incorporate these antigenic distances as a predictor for human population immunity as one measure to assess the risk of swine-to-human transmission.