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

Vittrup, Dorthe Maria; Jensen, Andreas; Sørensen, Jesper Kiehn; Zimakoff, Anne Cathrine; Malon, Michelle; Charabi, Salma; Johansen, Marie Ryberg; Simões, Eric A F; Kirkby, Nikolai Søren; Buus, Søren; Svensson, Jannet; Stensballe, Lone Graff

Vittrup, Dorthe Maria; Jensen, Andreas; Sørensen, Jesper Kiehn; Zimakoff, Anne Cathrine; Malon, Michelle; Charabi, Salma; Johansen, Marie Ryberg; Simões, Eric A F; Kirkby, Nikolai Søren; Buus, Søren; Svensson, Jannet; Stensballe, Lone Graff.

Afiliação

Vittrup DM; The Child and Adolescent Department, The University Hospital Herlev, Denmark.
Jensen A; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital "Rigshospitalet", Denmark.
Sørensen JK; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital "Rigshospitalet", Denmark.
Zimakoff AC; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital "Rigshospitalet", Denmark.
Malon M; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital "Rigshospitalet", Denmark.
Charabi S; The Child and Adolescent Clinic, The Juliane Marie Centre, The Danish National University Hospital "Rigshospitalet", Denmark.
Johansen MR; Department of Cardiology, Nordsjaellands Hospital, Hilleroed, Denmark.
Simões EAF; Department of Gynecology and Obstetrics, Nykoebing Falster Hospital, Denmark.
Kirkby NS; School of Medicine, and Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.
Buus S; Dept. of Microbiology, The Danish National University Hospital "Rigshospitalet", Denmark.
Svensson J; Dept. of Immunology, University of Copenhagen, Denmark.
Stensballe LG; The Child and Adolescent Department, The University Hospital Herlev, Denmark.

EClinicalMedicine ; 68: 102421, 2024 Feb.

Article em En | MEDLINE | ID: mdl-38292039

ABSTRACT

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 11 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, 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.