title: Novel polyvalent live vaccine against varicella-zoster and mumps virus infections.
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.
authors.affiliation: Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085; Kanonji Institute, Research Foundation for Microbial Diseases of Osaka University, 2-9-41, Yahata-cho, Kanonji, Kagawa, 768-0061.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.forename: Pranee
authors.initials: P
authors.lastname: Somboonthum
authors.forename: Kouki
authors.initials: K
authors.lastname: Murakami
authors.forename: Megumi
authors.initials: M
authors.lastname: Ota
authors.forename: Masaki
authors.initials: M
authors.lastname: Shoji
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gomi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D015707:HN Protein / Q000235:genetics / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009108:Mumps Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D015707:HN Protein; D009108:Mumps Vaccine; D050505:Mutant Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins
keywords: mumps; recombinant; vaccine; varicella-zoster virus