Characterization of recombinant influenza A virus as a vector expressing respiratory syncytial virus fusion protein epitopes

J Gen Virol. 2014 Sep;95(Pt 9):1886-1891. doi: 10.1099/vir.0.064105-0. Epub 2014 Jun 9.

Abstract

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and the elderly, and no vaccine against this virus has yet been licensed. Here, we report a recombinant PR8 influenza virus with the RSV fusion (F) protein epitopes of the subgroup A gene inserted into the influenza virus non-structural (NS) gene (rFlu/RSV/F) that was generated as an RSV vaccine candidate. The rescued viruses were assessed by microscopy and Western blotting. The proper expression of NS1, the NS gene product, and the nuclear export protein (NEP) of rFlu/RSV/F was also investigated using an immunofluorescent assay. The rescued virus replicated well in the MDCK kidney cell line, A549 lung adenocarcinoma cell line and CNE-2Z nasopharyngeal carcinoma cell line. BALB/c mice immunized intranasally with rFlu/RSV/F had specific haemagglutination inhibition antibody responses against the PR8 influenza virus and RSV neutralization test proteins. Furthermore, intranasal immunization with rFlu/RSV/F elicited T helper type 1-dominant cytokine profiles against the RSV strain A2 virus. Taken together, our findings suggested that rFlu/RSV/F was immunogenic in vivo and warrants further development as a promising candidate vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / immunology
  • COS Cells
  • Cell Line, Tumor
  • Chick Embryo
  • Chlorocebus aethiops
  • Dogs
  • Female
  • Gene Transfer Techniques
  • Genetic Vectors
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunization
  • Influenza A virus / genetics*
  • Influenza A virus / immunology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Viruses / genetics*
  • Respiratory Syncytial Viruses / immunology*
  • Viral Fusion Proteins / biosynthesis
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology

Substances

  • Antibodies, Viral
  • INS1 protein, influenza virus
  • Viral Fusion Proteins
  • Viral Nonstructural Proteins