title: A randomized trial to assess safety and immunogenicity of alternative formulations of a quadrivalent meningococcal (A, C, Y, and W-135) tetanus protein conjugate vaccine in toddlers.
abstract: BACKGROUND
  Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use.
  
  
  METHODS
  We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups--5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization.
  
  
  RESULTS
  All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers ≥ 8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator.
  
  
  CONCLUSIONS
  Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci.
authors.affiliation: Murdoch Children's Research Institute and Melbourne School of Population Health, The University of Melbourne, Melbourne, Australia. j.mcvernon@unimelb.edu.au
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.forename: Peter
authors.initials: P
authors.lastname: Richmond
authors.forename: Graham
authors.initials: G
authors.lastname: Reynolds
authors.forename: Michael
authors.initials: M
authors.lastname: Nissen
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Lambert
authors.forename: Helen
authors.initials: H
authors.lastname: Marshall
authors.forename: Thomas
authors.initials: T
authors.lastname: Papa
authors.forename: Christine
authors.initials: C
authors.lastname: Rehm
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001315:Australia; D004311:Double-Blind Method; D006801:Humans; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology; D038582:Neisseria meningitidis, Serogroup W-135 / Q000276:immunology; D038581:Neisseria meningitidis, Serogroup Y / Q000276:immunology; D011817:Rabbits; D058248:Serum Bactericidal Antibody Assay; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate