Novel polyvalent live vaccine against varicella-zoster and mumps virus infections

Microbiol Immunol. 2013 Oct;57(10):704-14. doi: 10.1111/1348-0421.12087.

Abstract

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is a highly immunogenic and safe live vaccine that has long been used worldwide. Because its genome is large, making it suitable for inserting foreign genes, vOka is considered a candidate vector for novel polyvalent vaccines. Previously, a recombinant vOka, rvOka-HN, that expresses mumps virus (MuV) hemagglutinin-neuraminidase (HN) was generated by the present team. rvOka-HN induces production of neutralizing antibodies against MuV in guinea pigs. MuV also expresses fusion (F) protein, which is important for inducing neutralizing antibodies, in its viral envelope. To induce a more robust immune response against MuV than that obtained with rvOka-HN, here an rvOka expressing both HN and F (rvOka-HN-F) was generated. However, co-expression of HN and F caused the infected cells to form syncytia, which reduced virus titers. To reduce the amount of cell fusion, an rvOka expressing HN and a mutant F, F(S195Y) were generated. Almost no syncytia formed among the rvOka-HN-F(S195Y)-infected cells and the growth of rvOka-HN-F(S195Y) was similar to that of the original vOka clone. Moreover, replacement of serine 195 with tyrosine had no effect on the immunogenicity of F in mice and guinea pigs. Although obvious augmentation of neutralizing antibody production was not observed after adding F protein to vOka-HN, the anti-F antibodies did have neutralizing activity. These data suggest that F protein contributes to induction of immune protection against MuV. Therefore this recombinant virus is a promising candidate vaccine for polyvalent protection against both VZV and MuV.

Keywords: mumps; recombinant; vaccine; varicella-zoster virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Chickenpox Vaccine / administration & dosage
  • Chickenpox Vaccine / immunology*
  • Chickenpox Vaccine / isolation & purification
  • Female
  • HN Protein / genetics
  • HN Protein / immunology
  • Herpesvirus 3, Human / genetics
  • Herpesvirus 3, Human / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mumps Vaccine / administration & dosage
  • Mumps Vaccine / immunology*
  • Mumps Vaccine / isolation & purification
  • Mutant Proteins / genetics
  • Mutant Proteins / immunology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / isolation & purification
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / isolation & purification
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Chickenpox Vaccine
  • HN Protein
  • Mumps Vaccine
  • Mutant Proteins
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • Viral Fusion Proteins