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

Pediatr Infect Dis J. 2012 Jan;31(1):e15-23. doi: 10.1097/INF.0b013e31823e1e34.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Australia
  • Double-Blind Method
  • Humans
  • Infant
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines* / administration & dosage
  • Meningococcal Vaccines* / adverse effects
  • Meningococcal Vaccines* / immunology
  • Neisseria meningitidis, Serogroup A / immunology
  • Neisseria meningitidis, Serogroup C / immunology
  • Neisseria meningitidis, Serogroup W-135 / immunology
  • Neisseria meningitidis, Serogroup Y / immunology
  • Rabbits
  • Serum Bactericidal Antibody Assay
  • Tetanus Toxoid* / administration & dosage
  • Tetanus Toxoid* / adverse effects
  • Tetanus Toxoid* / immunology
  • Treatment Outcome
  • Vaccination
  • Vaccines, Conjugate* / administration & dosage
  • Vaccines, Conjugate* / adverse effects
  • Vaccines, Conjugate* / immunology

Substances

  • Antibodies, Bacterial
  • Meningococcal Vaccines
  • Tetanus Toxoid
  • Vaccines, Conjugate