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Randomized Controlled Trial Comparative Study
Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12-15 months: A phase III, randomized, non-inferiority trial.
- MMR-161 Study Group.
- Vaccine. 2018 Sep 11; 36 (38): 5781-5788.
BackgroundThe potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation.MethodsIn this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMR-RIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and anti-mumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT).ResultsEach formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (-10.94%) was beyond the pre-defined limit of -10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles.ConclusionsOne dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a non-inferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-year-old children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.Copyright © 2018. Published by Elsevier Ltd.
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