Production of RA27/3 rubella vaccine and clinical results with the vaccine

Adaptation of rubella virus to human diploid cell strains was achieved in 1964, with attenuation in the same cells being accomplished by 1967. The production of rubella vaccine in HDCS is featured by the long period required to build up high titer. High multiplicity of infection gives optimal results. Since rubella virus does not produce a cytopathic effect in HDCS, virus harvests must be made blindly and titrated individually before pooling. A unique feature of this cell-virus relationship is the continuous virus production which takes place for months. For vaccine purposes, however, virus-containing supernatant fluids may be harvested each 48 hrs from the 5th to the 21st day post-infection. Lyophilization presents no particular problems and final titers in ampoules can be as high as 10(5.0) PFU, which represents about 100 subcutaneous doses. Control of rubella vaccine presents only the problem that viral CPE is absent or mild. Therefore the presence or absence of virus may have to be determined by interference. Titration of rubella virus produced in HDCS must be by plaquing in RK13 rabbit kidney cells or by interference in cynomolgus monkey kidney cells. Rubella vaccine (RA27/3 strain) produced in HDCS has been more immunogenic than other strains and retains an ability to infect intranasally as well as subcutaneously.