Comparison of the live attenuated mumps vaccine (Miyahara strain) with its preattenuated parental strain

Abstract

Live attenuated mumps vaccines have been developed by passaging the field isolates in cells that differ from the natural host. To study mumps viral (MuV) attenuation at the genomic level, we compared a live attenuated mumps vaccine (Miyahara strain) to its preattenuated parental strain. These two strains exhibited several phenotypic differences. The parental strain grew faster, reached a higher titer, and formed larger plaques and syncytia in Vero cells compared to the vaccine strain. In addition, intracranial injection of parental strain in neonatal rats resulted in greater ventricular enlargement than that caused by the vaccine strain. Four nucleotide changes leading to amino acid substitutions were found between the two viral genomes. One change is present in the N and L genes, respectively, and two in the F gene. The fusogenic activity of the cloned parental F gene evaluated by a cell-cell fusion assay was weaker than that of the vaccine F gene, and did not correspond to the activity caused by the living parental and vaccine strains. The transcriptional activities of N and L proteins were monitored by a CAT minigenome assay. Cloned parental N gene produced almost the same CAT activity as vaccine N, and cloned parental L gene produced significantly higher CAT activity than vaccine L. Thus among four nucleotide changes, the three occurring in N and F were not found to relate to the viral outcome, but we confirmed that at least one change in the L protein was involved in the growth phenotype of parental MuV.