Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context
Summary: Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5–7-month-old Danish infants were assigned in a 1...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2024-02-01
|
Series: | EClinicalMedicine |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023005989 |
_version_ | 1797348628814102528 |
---|---|
author | Dorthe Maria Vittrup Andreas Jensen Jesper Kiehn Sørensen Anne Cathrine Zimakoff Michelle Malon Salma Charabi Marie Ryberg Johansen Eric A.F. Simões Nikolai Søren Kirkby Søren Buus Jannet Svensson Lone Graff Stensballe |
author_facet | Dorthe Maria Vittrup Andreas Jensen Jesper Kiehn Sørensen Anne Cathrine Zimakoff Michelle Malon Salma Charabi Marie Ryberg Johansen Eric A.F. Simões Nikolai Søren Kirkby Søren Buus Jannet Svensson Lone Graff Stensballe |
author_sort | Dorthe Maria Vittrup |
collection | DOAJ |
description | Summary: Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5–7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.gov NCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4–5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3–1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9–1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8–4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5–7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark. |
first_indexed | 2024-03-08T12:08:27Z |
format | Article |
id | doaj.art-35db6baeff7f48ec949ea6820e497017 |
institution | Directory Open Access Journal |
issn | 2589-5370 |
language | English |
last_indexed | 2024-03-08T12:08:27Z |
publishDate | 2024-02-01 |
publisher | Elsevier |
record_format | Article |
series | EClinicalMedicine |
spelling | doaj.art-35db6baeff7f48ec949ea6820e4970172024-01-23T04:16:11ZengElsevierEClinicalMedicine2589-53702024-02-0168102421Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in contextDorthe Maria Vittrup0Andreas Jensen1Jesper Kiehn Sørensen2Anne Cathrine Zimakoff3Michelle Malon4Salma Charabi5Marie Ryberg Johansen6Eric A.F. Simões7Nikolai Søren Kirkby8Søren Buus9Jannet Svensson10Lone Graff Stensballe11The Child and Adolescent Department, The University Hospital Herlev, Denmark; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, Denmark; Corresponding author. Department for Children and Adolescents, The Danish National University Hospital “Rigshospitalet”, The Juliane Marie Center, Blegdamsvej 9, Copenhagen East 2100, Denmark.The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, DenmarkThe Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, DenmarkThe Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, DenmarkThe Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, DenmarkDepartment of Cardiology, Nordsjaellands Hospital, Hilleroed, DenmarkDepartment of Gynecology and Obstetrics, Nykoebing Falster Hospital, DenmarkSchool of Medicine, and Colorado School of Public Health, University of Colorado, Aurora, Colorado, USADept. of Microbiology, The Danish National University Hospital “Rigshospitalet”, DenmarkDept. of Immunology, University of Copenhagen, DenmarkThe Child and Adolescent Department, The University Hospital Herlev, Denmark; Steno Diabetes Centre Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, DenmarkThe Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital “Rigshospitalet”, Denmark; Department of Clinical Medicine, University of Copenhagen, DenmarkSummary: Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5–7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.gov NCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4–5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3–1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9–1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8–4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5–7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.http://www.sciencedirect.com/science/article/pii/S2589537023005989MMRMeasles vaccinationEarly immunizationImmunogenicityReactogenicity |
spellingShingle | Dorthe Maria Vittrup Andreas Jensen Jesper Kiehn Sørensen Anne Cathrine Zimakoff Michelle Malon Salma Charabi Marie Ryberg Johansen Eric A.F. Simões Nikolai Søren Kirkby Søren Buus Jannet Svensson Lone Graff Stensballe Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context EClinicalMedicine MMR Measles vaccination Early immunization Immunogenicity Reactogenicity |
title | Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context |
title_full | Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context |
title_fullStr | Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context |
title_full_unstemmed | Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context |
title_short | Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infantsResearch in context |
title_sort | immunogenicity and reactogenicity following mmr vaccination in 5 7 month old infants a double blind placebo controlled randomized clinical trial in 6540 danish infantsresearch in context |
topic | MMR Measles vaccination Early immunization Immunogenicity Reactogenicity |
url | http://www.sciencedirect.com/science/article/pii/S2589537023005989 |
work_keys_str_mv | AT dorthemariavittrup immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT andreasjensen immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT jesperkiehnsørensen immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT annecathrinezimakoff immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT michellemalon immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT salmacharabi immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT marierybergjohansen immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT ericafsimoes immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT nikolaisørenkirkby immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT sørenbuus immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT jannetsvensson immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext AT lonegraffstensballe immunogenicityandreactogenicityfollowingmmrvaccinationin57montholdinfantsadoubleblindplacebocontrolledrandomizedclinicaltrialin6540danishinfantsresearchincontext |