Dataset Information

Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study.

ABSTRACT:

Background

MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose.

Methods

In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines.

Results

Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected.

Conclusions

If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage.

SUBMITTER: Klein NP

PROVIDER: S-EPMC7192400 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study.

Klein Nicola P NP Abu-Elyazeed Remon R Povey Michael M Macias Parra Mercedes M Diez-Domingo Javier J Ahonen Anitta A Korhonen Tiina T Tinoco Juan-Carlos JC Weiner Leonard L Marshall Gary S GS Silas Peter E PE Sarpong Kwabena O KO Ramsey Keith P KP Fling John A JA Speicher David D Campos Maribel M Munjal Iona I Peltier Christopher C Vesikari Timo T Baccarini Carmen C Caplanusi Adrian A Gillard Paul P Carryn Stephane S Henry Ouzama O

Journal of the Pediatric Infectious Diseases Society 20200401 2

<h4>Background</h4>MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose.<h4>Methods</h4>In this phase III, observe ...[more]

PMID: 30849175

Similar Datasets

Project description:BackgroundThe reported coverage of the measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months.MethodsCross-sectional serological surveys of MMR antibodies were conducted by collecting epidemiological data in Zhejiang province, China in 2011. In total, 1015 participants were randomly selected from two surveillance sites. Serum MMR-specific immunoglobulin G levels were tested by enzyme-linked immunosorbent assay. The geometric mean titers and seroprevalence with 95% confidence intervals (CIs) were calculated by age and gender. Proportions of different dose of vaccine by age by vaccine were also identified. Statistically significant differences between categories were assessed by the Chi-square test.ResultsOver 95% seroprevalence rates of measles were seen in all age groups except <7 months infants. Children aged 5-9 years were shown lower seropositivity rates of mumps while elder adolescences and young adults were presented lower rubella seroprevalence. Especially, rubella seropositivity was significantly lower in female adults than in male. Nine measles cases were unvaccinated or unknown vaccination history. Among them, 66.67% (6/9) patients were aged 20-29 years while 33.33% (3/9) were infants aged 8-12 months. In addition, 57.75% (648/1122) patients with mumps were children aged 5-9 years, and 50.54% (94/186) rubella cases were aged 15-39 years.ConclusionsA timely two-dose MMR vaccination schedule is recommended, with the first dose at 8 months and the second dose at 18-24 months. An MR vaccination speed-up campaign may be necessary for elder adolescents and young adults, particularly young females.

Project description:BackgroundAssessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6-12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking.MethodsA commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5-7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019-2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).FindingsMeasles IgG levels compared to PRNT antibodies had a Pearson's correlation coefficient between 0.10-0.24. Seroprotection rates measured by ELISA in young infants were 10-14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline.InterpretationThe correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

Project description:BackgroundDespite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines.MethodsIn this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705.FindingsWe identified 3615 unique studies, 62 (1·7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·5-97·4; I2=91·1%) for measles, 93·3% (91·1-95·2; I2=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4-94·1; I2=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3-99·2; I2=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005-0·016; I2=85·2%) for measles, 0·024 (0·016-0·039; I2=94·7%) for mumps, and 0·012 (0·010-0·014; I2=93·3%) for rubella.InterpretationOur meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake.FundingEuropean Research Council.

Project description:ObjectiveTo test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months.DesignRandomised, double blinded, placebo controlled trial.SettingDenmark, a high income setting with low exposure to MMR.Participants6540 Danish infants aged 5 to 7 months.InterventionsInfants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only).Main outcome measuresHospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated.Results6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16).ConclusionFindings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months.Trial registrationEU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov NCT03780179.

Dataset Information

Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study.

Background

Methods

Results

Conclusions

Publications

Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets