title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Childrens Hospital, Dr. Horst Schmidt Clinic, Ludwig-Erhard-Straße 100, 65199 Wiesbaden, Germany. markus.knuf@hsk-wiesbaden.de
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
authors.forename: Olivier
authors.initials: O
authors.lastname: Romain
authors.forename: Klaus
authors.initials: K
authors.lastname: Kindler
authors.forename: Uta
authors.initials: U
authors.lastname: Walther
authors.forename: Phu-My
authors.initials: PM
authors.lastname: Tran
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Pankow-Culot
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischbach
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kieninger-Baum
authors.forename: Véronique
authors.initials: V
authors.lastname: Bianco
authors.forename: Yaela
authors.initials: Y
authors.lastname: Baine
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Miller
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D005858:Germany; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*
chemical_list: D022401:Meningococcal Vaccines; C576777:tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine