A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2-10 years

Abstract

Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2-10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2-10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine.

Trial registration: ClinicalTrials.gov NCT00427908.

Keywords: bactericidal activity; child; conjugate vaccine; immunogenicity; persistence; polysaccharide vaccine; safety; tetravalent meningococcal vaccine.

Figure 1. Participants’ progression through the study. ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine; ATP, according to protocol; TVC, total vaccinated cohort; N, number of children; *Reasons for non-eligibility: suboptimal responder re-vaccinated with a monovalent meningococcal serogroup C vaccine (n = 41); suboptimal responder who did not come to the booster vaccination visit (n = 2); consent withdrawal (n = 1); and acute leukemia (n = 1)

Figure 2. Incidence (with 95% CI) of solicited local and general symptoms occurring within 4 d after the first vaccination in children aged 2–5 y (A) or 6–10 y (B) (total vaccinated cohort). ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine. Error bars represent 95% confidence intervals