Development of Attenuated Rubella Virus Vaccines in Japan

Shishido, Akira; Ohtawara, Misao

doi:10.7883/yoken1952.29.227

Cited by 37 publications

(10 citation statements)

References 26 publications

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“…Four other attenuated strains of rubella virus have been developed and are used in Japan (Table 2) [19,20]. The BRD-2 vaccine strain has been developed at the National Vaccine and Serum Institute in Beijing, China [21].…”

Section: Development Of Rubella Vaccinesmentioning

confidence: 99%

Rubella vaccines: past, present and future

Best

1991

Epidemiol. Infect.

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The association between rubella in pregnancy and congenital anomalies was first reported 50 years ago, by N. McAlister Gregg, an Australian ophthalmologist [1]. During the next 20 years his findings were confirmed by others (reviewed in [2]). However, the first reports of the isolation of rubella virus in cell cultures and development of tests for neutralizing antibodies were not published until 1962 [3, 4]. Subsequent studies conducted in the UK and North America during a pandemic of rubella in 1963–4, were therefore able to make a more accurate estimate of the risks of maternal rubella at different stages of pregnancy. It was estimated that about 30000 rubella-damaged babies were born in the USA alone in 1963–4 [5]. This emphasized the importance of developing a vaccine to prevent infection in pregnancy and thereby, the birth of babies with rubella-induced congenital defects.

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Section: Development Of Rubella Vaccinesmentioning

confidence: 99%

Rubella vaccines: past, present and future

Best

1991

Epidemiol. Infect.

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“…SKI and SK2 strains were both derived from Matsuba strain. SK1 strain, although acceptably attenuated in elinicM trials, was withheld from approvM beeattse of its failure to meet the marker test as will be described below (Table 2) (12). It was subjected to further passages and cloning to yield SK2 strain which finally met the marker test and was granted licensure.…”

Section: Virus Strainsmentioning

confidence: 99%

“…was inversely correlated with the reactogenicity and/or transmissibility in clinical trials with candidate vaccine strains then being developed and several strains a¢ various levels of attenuation (12). In formulating the requirements for rubella vaccines in Japan, therefore, the absence of antibody response upon subcutaneous injection in rabbits and guinea pigs was adopted as the marker for attenuation (7).…”

Section: Introduetionmentioning

confidence: 99%

Inability of Japanese rubella vaccines to induce antibody response in rabbits is due to growth restriction at 39� C

Ohtawara

Kobune

Umino

et al. 1985

Archives of Virology

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We have compared the kinetic growth patterns of To-336, MEQ11, KRT, and SK2 rubella vaccine strains licensed in Japan at 37 degrees and 39 degrees C with those of progenitor wild strains of rubella virus. The growth of vaccine strains was depressed at 39 degrees C to a level about 3 log10 lower than that at 37 degrees C. The difference in virus titer attained by wild strains at 37 degrees and 39 degrees C was less than tenfold. The growth potential at 39 degrees C paralleled the immunogenic marker of rubella virus, i.e. the capability of virus to induce antibody response upon subcutaneous injection in rabbits for all wild and vaccine strains examined, including one strain at an intermediate level of attenuation. Several clones were isolated from the progeny produced by a vaccine strain during the growth at 39 degrees C. Among them were partial revertants in immunogenic marker as well as in the growth potential at 39 degrees C. It was concluded that the immunogenic marker of rubella virus in rabbits represented its capability to replicate at the body temperature of the animal.

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“…This means that therapeutic intervention on the cases of pregnant women were treated more frequently at the epidemic than usual on the basis of a threat to mothers' mental health of teratogenic effect of rubella infec tion. Thirdly, a possibility that the teratogenicity of the causative rubella virus differs from one epidemic to another may not be excluded (Kono, 1969;Shishido and Ohtawara, 1976).…”

Section: Frequency Of Crs Cases In Comparison With Incidences Of Repomentioning

confidence: 99%

“…Rubella vaccination program and the epidemic In 1969, the Japan Rubella Vaccine Research Commission (RVRC) was organized with a number of investigators headed by the author (A.S.), and the Commission undertook development of Japan-made rubella vaccine in coopera tion with several laboratories for vaccine production in Japan (Shishido and Ohtawara, 1976). The four live attenuated rubella vaccines were licensed in the autumn of 1975 by the authorities of MHW.…”

Section: Protective Effect O F Rubella Vaccination In the Epidemicmentioning

confidence: 99%