{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:04:45Z","timestamp":1783958685417,"version":"3.55.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["VACOP-8089-00019B"],"award-info":[{"award-number":["VACOP-8089-00019B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Measles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observed at increasing frequency.<\/jats:p><jats:p>The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15\u2009months, a timing chosen to avoid inhibition of the infant\u2019s immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6\u00a0months of age or earlier, thus increasing the risk of epidemics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Danish MMR trial is a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. Altogether<jats:italic>N<\/jats:italic>\u2009=\u20096500 infants aged 6\u00a0months will be randomly assigned to intramuscular vaccination with routine MMR (M-M-R VaxPro) or placebo (solvent only). According to the Danish Childhood vaccination program, all infants will receive a routine MMR vaccination at 15\u2009months of age. At randomization, 1\u00a0month later, and 1\u00a0month after routine MMR vaccination at 15\u2009months of age, a blood sample is drawn from app. 10% (<jats:italic>N<\/jats:italic>\u2009=\u2009600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1\u00a0month after MMR vaccination at 6\u00a0months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12\u2009months of age. Six weeks post randomization, all participants are interviewed regarding adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>The trial is registered in the EU Clinical Trials Registry. EudraCT registration number:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/trial\/2016-001901-18\/DK\">2016-001901-18<\/jats:ext-link>. Registered on 14 February 2017.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13063-020-04845-7","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T10:04:47Z","timestamp":1607594687000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Measles-mumps-rubella vaccine at 6\u2009months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6475-5224","authenticated-orcid":false,"given":"Dorthe Maria","family":"Vittrup","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Cathrine Lund","family":"Laursen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Malon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper Kiehn","family":"Soerensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Hjort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren","family":"Buus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannet","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lone Graff","family":"Stensballe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"4845_CR1","unstructured":"WHO. 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The legal guardians sign a written consent form before randomization. The informed consent is obtained by the special trained trial staff (doctors, nurses, medical students). If the child and biological mother participate in sample collection, two additional written consent forms are signed. The trial is not expected to be harmful in any way, but participants are insured by the Danish Act on the Right to Complain and Receive Compensation []. The trial is approved by the Danish Medicines Agency (EudraCT 2016-001901-18. J.no. 2016103428), the Committees on Biomedical Research Ethics (H-16041195) and by the Capital Region Data Regulation Unit (RH-2017-247, I-Suite no.: 05714). The trial is registered at ClinicalTrials.gov (NCT03780179) []. All protocol amendments are approved by the Committees on Biomedical Research Ethics before changes are implemented in the trial and the GCP-unit is notified when amendments are approved. The current version of the protocol is always available at the trial home page []. There will be made no changes in the protocol regarding the two co-primary outcomes or inclusion\/exclusion criteria. All analysis plans will be deposited with the DSMB prior to removal of blinding. There will be thoroughly accounted for analyses and findings in manuscripts regarding explorative analyses. Trial results (positive, negative and inconclusive) will be published in peer reviewed journals, and the results will be available on the trial homepage. Authorships will be awarded according to Vancouver rules.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The investigators have no financial or other competing interests. The financial sponsors have no influence on publications or termination of the trial.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1015"}}