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

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.