Selection of antigenically advanced variants of seasonal influenza viruses

Nat Microbiol. 2016 May 23;1(6):16058. doi: 10.1038/nmicrobiol.2016.58.

Abstract

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Antigenic Variation*
  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Evolution, Molecular
  • Ferrets / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immune Evasion
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology
  • Influenza, Human / epidemiology
  • Influenza, Human / prevention & control*
  • Mice
  • Orthomyxoviridae Infections / prevention & control
  • Seasons

Substances

  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines