TY - JOUR

T1 - Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting

T2 - study protocol for a randomized controlled trial

AU - Vittrup, Dorthe Maria

AU - Laursen, Anne Cathrine Lund

AU - Malon, Michelle

AU - Soerensen, Jesper Kiehn

AU - Hjort, Jakob

AU - Buus, Soren

AU - Svensson, Jannet

AU - Stensballe, Lone Graff

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Immunogenicity

KW - Indirect effects of vaccines

KW - Measles

KW - MMR

KW - Vaccine efficacy

KW - Vaccine safety

KW - Vaccine schedule

KW - Vaccinology

U2 - 10.1186/s13063-020-04845-7

DO - 10.1186/s13063-020-04845-7

M3 - Journal article

C2 - 33303011

AN - SCOPUS:85097413787

VL - 21

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 1015

ER -