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

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.

Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): A review of its immunogenicity, safety, co-administration, and antibody persistence

“…In the 6-10 years strata, using exploratory analysis, pain was reported more in the group receiving Men-PS (30%) compared to Men-ACWY-TT (20%) (P-value < 0.05). Moreover, in another phase III trial, involving children aged 2-10 years from Germany and France, solicited local AEs seemed to be more frequently reported than in the previously mentioned study 50 but similar to those reported by Knuf et al 42 Redness was the most common grade 3 solicited AE in both age strata. No statistically significant difference in local and general AEs was observed between those who received MenACWY-TT and those who received MenC-CRM with redness (35%) being the most common solicited AE in the 2-5 years strata and pain (44%) in the 6-10 years strata.…”

“…49 Again the immunogenicity of this vaccine in this same age group was evaluated in a phase III randomized study enrolling 415 subjects in Germany and France. 50 A single dose of MenACWY-TT was noninferior to MenC-CRM197 in terms of immunogenicity and vaccine response rates. 50 Moreover, MenACWY-TT was compared to another tetravalent conjugate vaccine MenACWY-DT in 1011 healthy 10 to 25 years old in a multi-centered phase II clinical trial in Canada and the United States.…”

“…50 A single dose of MenACWY-TT was noninferior to MenC-CRM197 in terms of immunogenicity and vaccine response rates. 50 Moreover, MenACWY-TT was compared to another tetravalent conjugate vaccine MenACWY-DT in 1011 healthy 10 to 25 years old in a multi-centered phase II clinical trial in Canada and the United States. Vaccine response was found non-inferior in the MenACWY-TT group.…”

“…None of the SAEs reported were considered related to vaccination. 50 In another randomized trial by Vesikari et al, 309 Finnish children aged 2 to 10 years were randomized to either receive MenACWY-TT or MenACWY PS vaccine. 49 Pain was the most common local solicited AE but the incidence was lower in those who received MenACWY-TT.…”

Prevention of Meningococcal Infection

“…У участни-ков исследования наблюдали значительное повышение среднего геометрического титров (СГТ) бактерицидных антител. Во всех серогруппах у 86-100% участников при исходно неопределяемых значениях титров СБА (<1:8) была отмечена сероконверсия, определяемая как 4-крат-ное (или более) увеличение титров антител спустя 28 дней после вакцинации [5,6] .…”