title: Analysis of the temperature sensitivity of Japanese rubella vaccine strain TO-336.vac and its effect on immunogenicity in the guinea pig.
abstract: The marker of Japanese domestic rubella vaccines is their lack of immunogenicity in guinea pigs. This has long been thought to be related to the temperature sensitivity of the viruses, but supporting evidence has not been described. In this study, we generated infectious clones of TO-336.vac, a Japanese domestic vaccine, TO-336.GMK5, the parental virus of TO-336.vac, and their mutants, and determined the molecular bases of their temperature sensitivity and immunogenicity in guinea pigs. The results revealed that Ser(1159) in the non-structural protein-coding region was responsible for the temperature sensitivity of TO-336.vac dominantly, while the structural protein-coding region affected the temperature sensitivity subordinately. The findings further suggested that the temperature sensitivity of TO-336.vac affected the antibody induction in guinea pigs after subcutaneous inoculation.
authors.affiliation: Laboratory of Rubella, Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address: k-okmt@nih.go.jp.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Experimental Animal Research, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ami
authors.affiliation: Division of Experimental Animal Research, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Suzaki
authors.affiliation: Laboratory of Rubella, Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuki
authors.affiliation: Laboratory of Rubella, Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sakata
authors.affiliation: Laboratory of Rubella, Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Laboratory of Rubella, Department of Virology III, National Institute of Infectious Diseases, Murayama Branch, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs / Q000276:immunology / Q000821:virology; D006801:Humans; D012409:Rubella / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012411:Rubella Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012412:Rubella virus / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D012411:Rubella Vaccine; D017361:Viral Nonstructural Proteins
keywords: Humoral immunogenicity; Rubella virus; Temperature sensitivity; Vaccine marker