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A Randomized Controlled Trial

Noni E. MacDonald, MD, FRCPC; Scott A. Halperin, MD; Barbara J. Law, MD, FRCPC; Bruce Forrest, MB, MD; Lisa E. Danzig, MD; Dan M. Granoff, MD

JAMA. 1998;280:1685-1689.

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.

From the University of Ottawa, Ottawa, Ontario (Dr MacDonald); Dalhousie University, Halifax, Nova Scotia (Dr Halperin); University of Manitoba, Winnipeg (Dr Law); Chiron Vaccines, Chiron Corp, Emeryville, Calif (Drs Forrest, Danzig, and Granoff); and Children's Hospital, Oakland Research Institute, Oakland, Calif (Dr Granoff).

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