Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016.

Marcus J Bolton,Eugenio J Abente,Jered A Stratton,Tavis K Anderson,Divya Venkatesh,Michael Zeller,Amy L Vincent,Nicola S Lewis

doi:10.1111/irv.12610

Abstract

BackgroundSix 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 and 2016.ObjectivesA broad panel of contemporary H3 viruses with uncharacterized antigenic motifs was selected across multiple clades within C‐IV to assess the impact of HA1 genetic diversity on the antigenic phenotype.MethodsHemagglutination inhibition (HI) assays were performed with isolates selected based on antigenic motif, tested against a panel of swine antisera, and visualized by antigenic cartography.ResultsA 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.ConclusionsAlthough 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.

Highlights

Influenza A virus (IAV) is an important respiratory pathogen of both humans and swine
Site-directed mutagenesis at these six amino acid positions in a prototype Clade IV (C-IV) H3 IAV-S strain confirmed that these six positions played a key role in defining the antigenic phenotype.[13]
Among the viruses tested with substitutions in the antigenic motif positions, we found that three new motifs (KYHNNK, KHHNNK, and SYKNYK) represented two potentially novel and distinct antigenic clusters

Summary

| INTRODUCTION

Influenza A virus (IAV) is an important respiratory pathogen of both humans and swine. Previous studies in search of molecular determinants responsible for antigenic drift in human H3 IAV identified seven amino acid positions (145, 155, 156, 158, 159, 189, and 193; H3 numbering throughout) in the HA protein that largely determined the antigenic phenotype.[10,11] A similar study with H3 IAV-S found that six of the seven positions (145, 155, 156, 158, 159, and 189) implicated in human IAV antigenic evolution were important for the antigenic phenotype of C-IV H3 IAV-S, and phenotypic differences were observed among co-circulating swine IAV.[12] Analysis by antigenic cartography revealed distinct antigenic groupings of viruses, termed antigenic clusters, and labeled by different colors for visualization. Site-directed mutagenesis at these six amino acid positions in a prototype C-IV H3 IAV-S strain confirmed that these six positions played a key role in defining the antigenic phenotype.[13] Trends in antigenic motif patterns over time revealed a predominance of viruses encoding Cyan antigenic cluster motifs in 2009, followed by a steady decline. The selected viruses contained uncharacterized motifs to determine the impact of amino acid substitutions at the six key sites as well as viruses with previously characterized antigenic motifs to validate previous observations

| METHODS

Findings

| DISCUSSION