Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine: an open-labeled, randomized trial in healthy Korean children.

PURPOSE: This study (NCT00751348) evaluated the immunogenicity and safety of a combined measles-mumps-rubella-varicella (MMRV) vaccine compared to co-administration of measles-mumps-rubella and varicella (MMR+V) vaccines in Korean children during their second year of life. MATERIALS AND METHODS: Healthy children aged 11-24 months received one dose of MMRV or MMR+V. Antibody titers against measles, mumps and rubella were measured using enzyme-linked immunosorbent assay and against varicella using an immunofluorescence assay. Parents/guardians recorded adverse events in diary cards for up to 43 days post-vaccination. The primary objective was to demonstrate non-inferiority of MMRV to MMR+V for all antigens in terms of seroconversion rates (SCRs), defined as a group difference with a lower limit of the 95% confidence interval (CI)>-10%. RESULTS: Of 474 subjects enrolled, 458 (MMRV, 301; MMR+V, 157) were included in the according-to-protocol cohort. For measles (98.0% vs. 99.4%), rubella (99.7% vs. 100%) and varicella (98.9% vs. 100%) SCRs, the lower limits of the 95% CIs for group differences were greater than -10%; however, for mumps SCRs (88.8% vs. 94.2%), it was -10.40%. The primary objective of non-inferiority in mumps SCRs was therefore not met, although the observed group difference in a post-hoc analysis of anti-mumps antibodies using a plaque reduction neutralization assay was 0.39% with a 95% CI lower limit of -4.03%. Adverse events occurred at comparable frequencies for both groups, except for more frequent fever in MMRV recipients. CONCLUSION: Based on the pre-specified non-inferiority criterion, SCRs of the MMRV vaccine were non-inferior to that elicited by MMR+V vaccines for all antigens except mumps.