Objective: to assess the optimal age to vaccinate with the quadrivalent meningococcal group A, C W and Y vaccine conjugated to tetanus toxoid (MenACWY).
Design: the study was part of a phase IV, open-label, randomized, controlled trial with a 1-year followup whose aim was to compare the immunogenicity of the monovalent meningococcal C (MenC) and the MenACWY conjugate vaccines.
Setting: single centre in Utrecht (Netherlands).
Study sample: the study included healthy children aged 10, 12 and 15 years (n = 83, 82 and 81, respectively) that had been vaccinated with the MenC vaccine between ages 14 months and 3 years.
Exclusion criteria: severe acute illness or fever at time of vaccination, antibiotic use in the 14 days prior to enrolment, chronic illness or medication that could interfere with results, allergy to vaccine components, history of invasive meningococcal disease (IMD), multiple meningococcal vaccinations, vaccinations in the prior month and pregnancy.
The study protocol consisted in the administration of the MenACWY vaccine with collection of blood samples for analysis before vaccination (T0) and 1 month (T1) and 1 year (T2) after vaccination.
Non-compliance with the study protocol occurred in four children aged 10 years, three aged 12 years and three aged 15 years that did not receive the MenACWY vaccine, and in six aged 10 years, 2 aged 12 years and 3 aged 15 years that did not adhere to the blood-sampling schedule. The losses to followup were less than 10% of the total children enrolled.
Outcome measurement: calculation of bactericidal geometric mean titres (GMTs) (≥ 1/8) and functional antibody titres (≥ 128). Measurement of MenA-, MenW- and MenY-specific IgE and MenW- and MenY-specific IgG1 and IgG2 levels. The authors described the laboratory methods used for the purpose. The within-group univariate statistical analysis consisted of linear regression adjusted for baseline values, using the Bonferroni correction for multiple comparisons and the χ2 test to compare proportions. The authors did not perform a multivariate analysis.
Main results: the baseline (T0) serum bactericidal assay using baby rabbit complement (rSBA) was ≥ 8 in 19.1%, 15.1% and 32% of the overall sample for MenA, MenW and MenY. The only difference based on age was in MenA, with higher SBA values at age 12 years. The GMTs had increased substantially at one month (T1) in all age groups (with higher titres against MenW and MenY in children aged 15 years). At 1 year (T2), all titres had decreased but remained significantly higher than baseline. Children aged 10 years had lower titres against MenW compared to those aged 12 and 15 years (P < .029 and P < .006, respectively). At 1 year, 95.1% of participants maintained titres ≥ 8 against all three serogroups, 2.2% against two serogroups and 2.7% against one serogroup.
Specific IgG levels were similar at T0, but at T1, while they increased in all age groups, they were higher for the three serogroups in 15-years group. One year later they had decreased, but they were still greater than baseline, and continued to be significantly higher for the 15-years group.
As for IgG subclasses, the trends were very similar to those observed for IgG.
Conclusion: the MenACWY vaccine induces robust immune responses up to 1 year after vaccination. The response was weaker in children vaccinated at age 10 years. To ensure individual protection as well as herd immunity, the authors recommend vaccination at age 12 years to protect against the rapid increase of MenW disease.
Conflicts of interest: one of the authors disclosed having received grants from GSK and Pfizer, and the others reported having no conflicts of interests.
Funding sources: Dutch Ministry of Health and grant from GSK; the funders had no role in study design, data collection and analysis, the decision to publish or the preparation of the manuscript.