Canine influenza viruses with modified NS1 proteins for the development of live-attenuated vaccines

Virology. 2017 Jan:500:1-10. doi: 10.1016/j.virol.2016.10.008. Epub 2016 Oct 15.

Abstract

Canine Influenza Virus (CIV) H3N8 is the causative agent of canine influenza, a common and contagious respiratory disease of dogs. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV H3N8. However, live-attenuated influenza vaccines (LAIVs) are known to provide better immunogenicity and protection efficacy than IIVs. Influenza NS1 is a virulence factor that offers an attractive target for the preparation of attenuated viruses as LAIVs. Here we generated recombinant H3N8 CIVs containing truncated or a deleted NS1 protein to test their potential as LAIVs. All recombinant viruses were attenuated in mice and showed reduced replication in cultured canine tracheal explants, but were able to confer complete protection against challenge with wild-type CIV H3N8 after a single intranasal immunization. Immunogenicity and protection efficacy was better than that observed with an IIV. This is the first description of a LAIV for the prevention of H3N8 CIV in dogs.

Keywords: Canine influenza virus; Canine tracheal explant; Inactivated influenza vaccines; Influenza A virus; Live-attenuated influenza vaccines; NS1 deficient influenza viruses; Non-structural protein 1; Reverse genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Dog Diseases / immunology
  • Dog Diseases / prevention & control*
  • Dog Diseases / virology
  • Dogs
  • Female
  • Humans
  • Influenza A Virus, H3N8 Subtype / genetics
  • Influenza A Virus, H3N8 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology*
  • Viral Nonstructural Proteins / administration & dosage
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Viral
  • INS1 protein, influenza virus
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins