Immunogenicity and safety of the quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) in 2-10-year-old children: results of an open, randomised, controlled study

Markus Knuf, Olivier Romain, Klaus Kindler, Uta Walther, Phu-My Tran, Heidemarie Pankow-Culot, Thomas Fischbach, Dorothee Kieninger-Baum, Véronique Bianco, Yaela Baine, Jacqueline Miller, Markus Knuf, Olivier Romain, Klaus Kindler, Uta Walther, Phu-My Tran, Heidemarie Pankow-Culot, Thomas Fischbach, Dorothee Kieninger-Baum, Véronique Bianco, Yaela Baine, Jacqueline Miller

Abstract

In Europe, the introduction of monovalent meningococcal serogroup C (MenC) conjugate vaccines has resulted in a significant decline in MenC invasive disease. However, given the potential for strain evolution and increasing travel to areas of high endemicity, protection against additional serogroups is needed. In this study, the immunogenicity, measured by a serum bactericidal activity assay using rabbit complement (rSBA), and the safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were compared to that of a licensed monovalent MenC conjugate vaccine (MenC-CRM₁₉₇) in children 2-10 years of age. Children were randomised (3:1) to receive a single dose of either MenACWY-TT or MenC-CRM₁₉₇. Non-inferiority of the immunogenicity of MenACWY-TT versus MenC-CRM₁₉₇ in terms of rSBA-MenC vaccine response was demonstrated. Exploratory analyses suggested that rSBA-MenC geometric mean titres adjusted for pre-vaccination titres were lower in children vaccinated with MenACWY-TT compared to MenC-CRM₁₉₇. Nevertheless, at 1 month post-vaccination, ≥99.3 % of the children who received MenACWY-TT had rSBA titres ≥1:128 for each of the four vaccine serogroups, which is the more conservative correlate of protection. The reactogenicity and safety profile of MenACWY-TT was clinically acceptable and no serious adverse events considered related to vaccination were reported throughout the study.

Conclusion: When administered to European school-age children, MenACWY-TT has a clinically acceptable safety profile and, when compared with MenC-CRM₁₉₇, the potential to broaden protection against meningococcal disease caused by serogroups A, W-135 and Y while maintaining protection against MenC. This study has been registered at www.clinicaltrials.gov NCT00674583.

Figures

Fig. 1
Fig. 1
Participant flow. ACWY-TT group of children who received one dose of MenACWY-TT at month 0, MenC-CRM group of children who received one dose of MenC-CRM197 at month 0, ATP according to protocol, TVC total vaccinated cohort, N number of children
Fig. 2
Fig. 2
Reverse cumulative curves for the ACWY-TT and MenC-CRM groups for rSBA-MenA (a), rSBA-MenC (b), rSBA-MenW-135 (c) and rSBA-MenY (d) (ATP cohort for immunogenicity). ACWY-TT group of children who received one dose of MenACWY-TT at month 0, MenCCRM group of children who received one dose of MenC-CRM197 at month 0. PRE pre-vaccination at month 0, PI(M1) post-vaccination at month 1
Fig. 3
Fig. 3
Percentage of children in the 2–5 years age stratum (a) and in the 6–10 years age stratum (b) experiencing solicited local and general symptoms within the 4-day post-vaccination period (total vaccinated cohort). ACWY-TT group of children who received one dose of MenACWY-TT at month 0, MenC-CRM group of children who received one dose of MenC-CRM197 at month 0. Error bars represent 95 % confidence intervals

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