An attenuated strain of rubella virus was established by passage of the virus in primary African green monkey kidney cell cultures (GMK). In the first rubella vaccine clinical trial with seventy-seventh passage GMK material, none of eight inoculated children evidenced rubella-like illness and all developed antibody. The vaccine-induced infections were not transmitted to intimate contacts. Trials with large numbers of children confirmed the early findings of safety and immunogenicity of the vaccine. The second successfully attenuated virus, the Benoit strain, was developed by Hilleman and co-workers by adapting low GMK passages of virus to duck embryo cell cultures (DE). The Benoit strain, tested at several levels of tissue culture passage, designated A, B, C, D, and E, served as a clear demonstration of how rubella virus is modified by passage in mammalian or avian cells. Vaccines prepared from A and B level materials were not suitable, since they were either communicable or produced rubella-like symptoms. The C and D level materials were attenuated, but the higher passaged E level vaccine was termed "over-attenuated" since it induced antibody in only 60% of the vaccinees. More recently, the Cendehill strain, attenuated in primary rabbit kidney cell cultures (RK) and the RA 27/3 strain, attenuated in WI-38 cells, have been tested clinically.
Vaccines which are now being produced by biologics manufacturers and considered candidates for license in the United States are: the HPV-77 strain passed 5 times in DE(HPV-77, DE5); the HPV-77 strain passed 12 times in dog kidney (DK) cell cultures (HPV-77, DK12), and the Cendehill strain passed 4 times in GMK and 53 times in RK (Cendehill GMK 4, RK 53). With each of these vaccines, antibody was detected in 90 to 100% of recipients.
Fully attenuated rubella virus vaccines have not produced significant clinical reactions in children. However, mild rubella-like symptoms have been observed in adult women receiving vaccine; transient rashes, lymphadenopathy, arthralgia, and arthritis have been observed. Since the risk of spread of attenuated virus to the fetus in vaccinated women cannot be readily determined, the use of the vaccine during pregnancy would be potentially hazardous.
Intranasal challenge of HPV-77 vaccinees with natural rubella virus demonstrated that vaccine-induced antibodies were protective against the clinical and virologic manifestations of rubella. Observation of vaccinated children over a 3-year period has demonstrated little evidence of a decline in the antibodies.
Trials with a live attenuated rubella virus vaccine, Cendehill strain
