Genetic and subunit vaccines based on the stem domain of the equine influenza hemagglutinin provide homosubtypic protection against heterologous strains

Vaccine. 2018 Mar 14;36(12):1592-1598. doi: 10.1016/j.vaccine.2018.02.019. Epub 2018 Feb 15.

Abstract

H3N8 influenza virus strains have been associated with infectious disease in equine populations throughout the world. Although current vaccines for equine influenza stimulate a protective humoral immune response against the surface glycoproteins, disease in vaccinated horses has been frequently reported, probably due to poor induction of cross-reactive antibodies against non-matching strains. This work describes the performance of a recombinant protein vaccine expressed in prokaryotic cells (ΔHAp) and of a genetic vaccine (ΔHAe), both based on the conserved stem region of influenza hemagglutinin (HA) derived from A/equine/Argentina/1/93 (H3N8) virus. Sera from mice inoculated with these immunogens in different combinations and regimes presented reactivity in vitro against highly divergent influenza virus strains belonging to phylogenetic groups 1 and 2 (H1 and H3 subtypes, respectively), and conferred robust protection against a lethal challenge with both the homologous equine strain (100%) and the homosubtypic human strain A/Victoria/3/75 (H3N2) (70-100%). Animals vaccinated with the same antigens but challenged with the human strain A/PR/8/34 (H1N1), belonging to the phylogenetic group 1, were not protected (0-33%). Combination of protein and DNA immunogens showed higher reactivity to non-homologous strains than protein alone, although all vaccines were permissive for lung infection.

Keywords: Conserved epitopes; Cross-protection; Equine influenza virus; Hemagglutinin stem region; Lethal challenge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cross Protection / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control*
  • Horse Diseases / virology
  • Horses
  • Humans
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N8 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Orthomyxoviridae Infections / veterinary*
  • Recombinant Proteins
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology*

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Recombinant Proteins
  • Vaccines, Subunit
  • Vaccines, Synthetic