Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011-2018

Sci Rep. 2019 Feb 25;9(1):2676. doi: 10.1038/s41598-019-39276-1.

Abstract

Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011-2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antigens, Viral / immunology*
  • Ferrets / immunology
  • Ferrets / virology
  • Glycosylation
  • Hemagglutination Inhibition Tests / methods*
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Immune Sera / immunology
  • Influenza A Virus, H3N2 Subtype / classification
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / physiology
  • Influenza Vaccines / immunology
  • Influenza, Human / diagnosis
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Neutralization Tests / methods*
  • Phylogeny

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immune Sera
  • Influenza Vaccines