Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial
Abstract Background 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 child...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-020-04845-7 |
| _version_ | 1818435360683720704 |
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| author | Dorthe Maria Vittrup Anne Cathrine Lund Laursen Michelle Malon Jesper Kiehn Soerensen Jakob Hjort Soren Buus Jannet Svensson Lone Graff Stensballe |
| author_facet | Dorthe Maria Vittrup Anne Cathrine Lund Laursen Michelle Malon Jesper Kiehn Soerensen Jakob Hjort Soren Buus Jannet Svensson Lone Graff Stensballe |
| author_sort | Dorthe Maria Vittrup |
| collection | DOAJ |
| description | Abstract Background 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. The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15 months, a timing chosen to avoid inhibition of the infant’s 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 months of age or earlier, thus increasing the risk of epidemics. Methods 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 N = 6500 infants aged 6 months 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 months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15 months of age, a blood sample is drawn from app. 10% (N = 600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12 months of age. Six weeks post randomization, all participants are interviewed regarding adverse events. Trial registration The trial is registered in the EU Clinical Trials Registry. EudraCT registration number: 2016-001901-18 . Registered on 14 February 2017. |
| first_indexed | 2024-12-14T16:51:39Z |
| format | Article |
| id | doaj.art-79e969b33f5549359fa951439eb2e690 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-14T16:51:39Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-79e969b33f5549359fa951439eb2e6902022-12-21T22:54:03ZengBMCTrials1745-62152020-12-012111810.1186/s13063-020-04845-7Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trialDorthe Maria Vittrup0Anne Cathrine Lund Laursen1Michelle Malon2Jesper Kiehn Soerensen3Jakob Hjort4Soren Buus5Jannet Svensson6Lone Graff Stensballe7The Child and Adolescent Department, The University Hospital HerlevThe Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital “Rigshospitalet”The Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital “Rigshospitalet”The Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital “Rigshospitalet”Department of Clinical Medicine, Health, Aarhus UniversityDepartment of Immunology and Microbiology, University of CopenhagenThe Child and Adolescent Department, The University Hospital HerlevThe Child and Adolescent Clinic, The Juliane Marie Center, The Danish National University Hospital “Rigshospitalet”Abstract Background 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. The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15 months, a timing chosen to avoid inhibition of the infant’s 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 months of age or earlier, thus increasing the risk of epidemics. Methods 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 N = 6500 infants aged 6 months 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 months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15 months of age, a blood sample is drawn from app. 10% (N = 600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12 months of age. Six weeks post randomization, all participants are interviewed regarding adverse events. Trial registration The trial is registered in the EU Clinical Trials Registry. EudraCT registration number: 2016-001901-18 . Registered on 14 February 2017.https://doi.org/10.1186/s13063-020-04845-7MeaslesMMRVaccinologyImmunogenicityIndirect effects of vaccinesVaccine efficacy |
| spellingShingle | Dorthe Maria Vittrup Anne Cathrine Lund Laursen Michelle Malon Jesper Kiehn Soerensen Jakob Hjort Soren Buus Jannet Svensson Lone Graff Stensballe Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial Trials Measles MMR Vaccinology Immunogenicity Indirect effects of vaccines Vaccine efficacy |
| title | Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial |
| title_full | Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial |
| title_fullStr | Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial |
| title_full_unstemmed | Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial |
| title_short | Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial |
| title_sort | measles mumps rubella vaccine at 6 months of age immunology and childhood morbidity in a high income setting study protocol for a randomized controlled trial |
| topic | Measles MMR Vaccinology Immunogenicity Indirect effects of vaccines Vaccine efficacy |
| url | https://doi.org/10.1186/s13063-020-04845-7 |
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