title: Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial.
abstract: BACKGROUND
  Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem.
  
  
  OBJECTIVE
  To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine.
  
  
  METHODS
  A multicenter, randomized, observer-blinded controlled trial.
  
  
  METHODS
  Urban and suburban family medicine or pediatric practices.
  
  
  METHODS
  Two hundred eleven healthy toddlers aged 15 to 23 months.
  
  
  METHODS
  Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later.
  
  
  METHODS
  IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody.
  
  
  RESULTS
  In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses.
  
  
  CONCLUSIONS
  Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.
authors.affiliation: University of Ottawa, Ontario, Canada. macdonaldvn@cheo.on.ca
authors.forename: N E
authors.initials: NE
authors.lastname: MacDonald
authors.forename: S A
authors.initials: SA
authors.lastname: Halperin
authors.forename: B J
authors.initials: BJ
authors.lastname: Law
authors.forename: B
authors.initials: B
authors.lastname: Forrest
authors.forename: L E
authors.initials: LE
authors.lastname: Danzig
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D007156:Immunologic Memory; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control*; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012703:Serotyping; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate