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Elucidation of the full genetic information of Japanese rubella vaccines and the genetic changes associated with in vitro and in vivo vaccine virus phenotypes.

Abstract：

:Rubella is a mild disease characterized by low-grade fever, and a morbilliform rash, but causes congenital defects in neonates born from mothers who suffered from rubella during the pregnancy. After many passages of wild-type rubella virus strains in various types of cultured cells, five live attenuated rubella vaccines were developed in Japan. An inability to elicit anti-rubella virus antibodies in experimentally infected animals was used as an in vivo marker phenotype of Japanese rubella vaccines. All Japanese rubella vaccine viruses exhibit a temperature-sensitive (ts) phenotype, and replicate very poorly at a high temperature. We determined the entire genome sequences of three Japanese rubella vaccines (Matsuba, TCRB19, and Matsuura), thereby completing the sequencing of all five Japanese rubella vaccines. In addition, the entire genome sequences of three vaccine progenitors were determined. Comparative nucleotide sequence analyses revealed mutations that were introduced into the genomes of the TO-336 and Matsuura vaccines during their production by laboratory passaging. Analyses involving cellular expression of viral P150 nonstructural protein-derived peptides revealed that the N1159S mutation conferred the ts phenotype on the TO-336 vaccine, and that reduced thermal stability of the P150 protease domain was a cause of the ts phenotype of some rubella vaccine viruses. The ts phenotype of vaccine viruses was not necessarily correlated with their inability to elicit humoral immune responses in animals. Therefore, the molecular mechanisms underlying the inability of these vaccines to elicit humoral responses in animals are more complicated than the previously considered mechanism involving the ts phenotype as the major cause.

journal_name

Vaccine

journal_title

Vaccine

authors

Otsuki N,Abo H,Kubota T,Mori Y,Umino Y,Okamoto K,Takeda M,Komase K

doi

10.1016/j.vaccine.2011.01.016

subject

Has Abstract

pub_date

2011-02-24 00:00:00

pages

1863-73

issue

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(11)00044-2

journal_volume

pub_type

杂志文章

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Elucidation of the full genetic information of Japanese rubella vaccines and the genetic changes associated with in vitro and in vivo vaccine virus phenotypes.