Location: Virus and Prion ResearchTitle: Antigenic distance between North American swine and human seasonal H3N2 influenza A viruses as an indication of zoonotic risk to humans
|SOUZA, CARINE - Orise Fellow
|CHANG, JENNIFER - Orise Fellow
|VENKATESH, DIVYA - Royal Veterinary College
|LEWIS, NICOLA - Royal Veterinary College
|PEKOSZ, ANDREW - Johns Hopkins University
|SHAW-SALIBA, KATHRYN - Johns Hopkins University School Of Medicine
|ROTHMAN, RICHARD - Johns Hopkins University School Of Medicine
|CHEN, KUAN-FU - Chang Gung Memorial Hospital
Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2021
Publication Date: 1/26/2022
Citation: Souza, C.K., Anderson, T.K., Chang, J., Venkatesh, D., Lewis, N.S., Pekosz, A., Shaw-Saliba, K., Rothman, R.E., Chen, K., Baker, A.L. 2022. Antigenic distance between North American swine and human seasonal H3N2 influenza A viruses as an indication of zoonotic risk to humans. Journal of Virology. 96(2). Article e01374-21. https://doi.org/10.1128/JVI.01374-21.
Interpretive Summary: Human H3N2 influenza A viruses (IAV) spread to pigs in North America in the 1990s and more recently in the 2010s. These cross-species events led to sustained circulation of H3N2 in swine and increased IAV diversity in pig populations. The evolution in swine H3N2 led to a reduced similarity with human seasonal H3N2 and the vaccine strains used to protect human populations. We quantified the antigenic phenotypes and found that North American swine H3N2 lineages retained more antigenic similarity to historical human vaccine strains from the decade of incursion but had substantial difference compared with more recent human vaccine strains. Additionally, pandemic preparedness vaccine strains developed for public health also demonstrated a loss in similarity with these contemporary swine strains. Lastly, post-exposure and post-vaccination human sera revealed that although these adults had antibodies against human H3N2 strains, many had limited immunity to swine H3N2, particularly the viruses from the 1990s, especially older adults born before 1970. These antigenic assessments of swine H3N2 provide critical information for pandemic preparedness and candidate vaccine development.
Technical Abstract: Human-to-swine influenza A virus (IAV) transmission events repeatedly occur, some leading to sustained transmission and increased IAV diversity in pig populations. Human-to-swine H3N2 IAV introductions in North America occurred in the 1990s and more recently in the 2010s. These lineages were subsequently associated with zoonotic infections, highlighting the need to understand the antigenic diversity of IAV in swine. Here, we quantified the antigenic distances between swine H3N2 and human seasonal vaccine strains (1973-2014) using a panel of monovalent antisera raised in pigs in hemagglutination inhibition (HI) assays. Antigenic distances between viruses were calculated in antigenic units (AU), in which 1 AU is equivalent to a 2-fold difference in HI cross-reactivity. In addition, antisera raised in ferrets against candidate vaccine virus (CVV) and human seasonal vaccine were used to quantify the cross-reactivity with swine H3N2 strains. Swine H3N2 lineages retained closest antigenic distance to human vaccine strains from the decade of incursion: swine H3N2 from the 1990s lineages were antigenically more similar to human vaccine strains of the same decade (A/Beijing/32/92 or A/Wuhan/359/95) but had substantial distance from recent human vaccine strains. In contrast, the swine H3 lineages of 2010s were closer to the A/Victoria/361/11 human vaccine strain or A/Hong Kong/4801/2014 and most antigenically distant from human vaccine strains prior to 2007. Swine lineages from the 1990s and 2010s demonstrated significant fold-reduction compared with the homologous HI titer of the nearest CVV. Putative human population immunity against representative North American swine H3N2 strains were then assessed using HI assay data with human sera. Post-exposure and post-vaccination human sera cohorts demonstrated limited cross-reactivity to swine H3N2 strains from the 1990s (3.1990.4a and 4b), especially older adults born before 1970s. These antigenic data identified swine strains to which humans are likely to lack population immunity or would not be covered by a human seasonal IAV vaccine or by current CVV.