Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infants

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Citations (Scopus)
12 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number102421
JournalEClinicalMedicine
Volume68
Number of pages12
ISSN2589-5370
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • Early immunization
  • Immunogenicity
  • Measles vaccination
  • MMR
  • Reactogenicity

Cite this