Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

JAMA. 1998 Nov 18;280(19):1685-9. doi: 10.1001/jama.280.19.1685.


Context: 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.

Design: A multicenter, randomized, observer-blinded controlled trial.

Setting: Urban and suburban family medicine or pediatric practices.

Participants: Two hundred eleven healthy toddlers aged 15 to 23 months.

Intervention: 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.

Main outcome measures: 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.

Publication types

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

MeSH terms

  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Hepatitis B Vaccines / immunology
  • Humans
  • Immunization, Secondary
  • Immunoglobulin G / analysis
  • Immunoglobulin G / immunology*
  • Immunologic Memory
  • Infant
  • Meningococcal Infections / prevention & control*
  • Neisseria meningitidis / classification
  • Neisseria meningitidis / immunology*
  • Polysaccharides, Bacterial / immunology*
  • Serotyping
  • Vaccination
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology*


  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Hepatitis B Vaccines
  • Immunoglobulin G
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate