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

Authors

  • Masaaki Matsuura,

    1. Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka
    2. Kanonji Institute, Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa
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    • These authors contributed equally to this work.
  • Pranee Somboonthum,

    1. Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka
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    • These authors contributed equally to this work.
  • Kouki Murakami,

    1. Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka
    2. Kanonji Institute, Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa
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  • Megumi Ota,

    1. Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka
    2. Division of Clinical Virology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe
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  • Masaki Shoji,

    1. Division of Biomedical Research, Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Ibaraki, Osaka
    2. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka
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  • Kenji Kawabata,

    1. Division of Biomedical Research, Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Ibaraki, Osaka
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  • Hiroyuki Mizuguchi,

    1. Division of Biomedical Research, Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Ibaraki, Osaka
    2. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka
    3. Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Osaka, Japan
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  • Yasuyuki Gomi,

    1. Kanonji Institute, Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa
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  • Koichi Yamanishi,

    1. National Institute of Biomedical Innovation, Ibaraki, Osaka
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  • Yasuko Mori

    Corresponding author
    1. Division of Clinical Virology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe
    • Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka
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Correspondence

Yasuko Mori, Division of Clinical Virology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Tel: +81 78 382 6272; Fax: +81 78 382 6879; email: ymori@med.kobe-u.ac.jp

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.

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