Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis

BACKGROUND: Despite 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. METHODS: In 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. FINDINGS: We 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; I(2)=91·1%) for measles, 93·3% (91·1–95·2; I(2)=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4–94·1; I(2)=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3–99·2; I(2)=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005–0·016; I(2)=85·2%) for measles, 0·024 (0·016–0·039; I(2)=94·7%) for mumps, and 0·012 (0·010–0·014; I(2)=93·3%) for rubella. INTERPRETATION: Our 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. FUNDING: European Research Council.