A novel M2e based flu vaccine formulation for dogs

PLoS One. 2013 Oct 2;8(10):e77084. doi: 10.1371/journal.pone.0077084. eCollection 2013.

Abstract

Background: The USA 2004 influenza virus outbreak H3N8 in dogs heralded the emergence of a new disease in this species. A new inactivated H3N8 vaccine was developed to control the spread of the disease but, as in humans and swine, it is anticipated that the virus will mutate shift and drift in the dog population. Therefore, there is a need for a vaccine that can trigger a broad protection to prevent the spread of the virus and the emergence of new strains.

Methodology and principal findings: The universal M2e peptide is identical in almost all the H3N8 influenza strains sequenced to date and known to infect dogs. This epitope is therefore a good choice for development of a vaccine to provide broad protection. Malva mosaic virus (MaMV) nanoparticles were chosen as a vaccine platform to improve the stability of the M2e peptide and increase its immunogenicity in animals. The addition of an adjuvant (OmpC) purified from Salmonella typhi membrane in the vaccine formulation increased the immune response directed to the M2e peptide significantly and enlarged the protection to include the heterosubtypic strain of influenza in a mouse model. An optimal vaccine formulation was also shown to be immunogenic in dogs.

Conclusions and significance: The MaMV vaccine platform triggered an improved immune response directed towards the universal M2e peptide. The adjuvant OmpC increased the immune response to the M2e peptide and protection to a heterosubtypic influenza strain that harbors a different M2e peptide in a mouse model. Antibodies generated by the vaccine formulation showed cross-reactivity with M2e peptides derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows a potential for commercialization of a new M2e based vaccine in dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood*
  • Conserved Sequence
  • Cross Protection
  • Dog Diseases / immunology
  • Dog Diseases / prevention & control*
  • Dog Diseases / virology
  • Dogs
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N8 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / immunology
  • Influenza A Virus, H9N2 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mosaic Viruses / genetics
  • Mosaic Viruses / immunology
  • Nanoparticles / chemistry
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • Porins / administration & dosage
  • Vaccination*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • OmpC protein
  • Porins
  • Viral Envelope Proteins

Grants and funding

This research project was funded by the ‘Programme de soutient à la valorisation et au transfert (PSVT)’ of the ‘Ministère du Développement économique, de l’innovation et de l’exportation (MDEIE)’ of Quebec/Canada and the grant Natural Sciences and Engineering Research Council (NSERC)- Canada (grant # 269445 - 03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.