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

Abstract

PurposeThis 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 MethodsHealthy 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%.ResultsOf 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.ConclusionBased 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.

A 16-year review of seroprevalence studies on measles and rubella

“…Of these six, two [59,86] also evaluated the rubella antibody response to vaccination. A further five measles and three rubella studies reviewed the levels of protection in populations stratified into different age groups.…”

“…Six of the measles surveys [10,59,60,77,86,89] evaluating vaccination programmes compared the efficacy of different vaccines and/or vaccine schedules. Of these six, two [59,86] also evaluated the rubella antibody response to vaccination.…”

Risk of febrile seizure after measles–mumps–rubella–varicella vaccine: A systematic review and meta-analysis

“…Within a smaller risk window of 7-10 days after first vaccine dose, 11 febrile seizure cases and 9 vaccine related febrile seizure cases were reported respectively in 13,129 and 25,433 vaccinated children aged 9-24 months [26][27][28][29][30][33][34][35][37][38][39][40][41][42][43][45][46][47][48][49][50]. In 16 studies informed the prognosis [27][28][29][30][31][32][33][34][35][36][37]39,40,45,48,49], a total of 42 febrile seizures were reported, and these cases all recovered without any sequelae.…”

“…Twenty-three clinical trials were published and the others [26,27] were unpublished. Twenty-nine clinical trials [26][27][28][29][30][31][32][33][34][35][37][38][39][40][41][42][43][44][45][46][47][48][49][50] reported the incidence of febrile seizure or vaccine related febrile seizure within 0-28, 0-42 or 0-56 days (0-28/42/56 days) after first MMRV vaccine dose in healthy children aged 9-24 months, twenty-five of them [26][27][28][29][30][33][34][35][37][38][39][40][41][42][43][45][46][47][48][49][50] also reported the incidence within a smaller risk window of 7 to 10 days (7-10 days) after vaccination. Children in 17 clinical trials …”

“…Twenty-one RCTs [26][27][28][29][30][31][32][33][34][35][39][40][41]43,47,49,50] were included in the meta-analysis to analyze the incidence of febrile seizure and vaccine related febrile seizure within 0-28/42/56 days after first MMRV vaccine dose in healthy children aged 9-24 months ( Table 2), nineteen of them [26][27][28][29][30][33][34][35][39][40][41]43,47,49,50] compared the incidence in a risk window of 7-10 days after vaccination. During 0-28/42/56 days after first MMRV dose, pooled incidence of febrile seizure was under 2.51‰ in all groups.…”