Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines

PLoS One. 2016 Oct 6;11(10):e0164245. doi: 10.1371/journal.pone.0164245. eCollection 2016.

Abstract

Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Carps
  • Cell Line
  • Dogs
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hemagglutinins / genetics
  • Hemagglutinins / immunology
  • Hemagglutinins / metabolism
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Novirhabdovirus / immunology*
  • Novirhabdovirus / metabolism
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Plasmids / genetics
  • Plasmids / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Vaccination
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Neutralizing
  • Hemagglutinins
  • Recombinant Proteins
  • Vaccines, Synthetic

Grants and funding

Dr RN Rouxel has been financially supported by ABIVAX France.