Persistence of group C anticapsular antibodies two to three years after immunization with an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine

Abstract

Background: An investigational quadrivalent (A, C, Y and W-135) meningococcal conjugate (MC-4) vaccine was reported to be more immunogenic in 2-year-olds than the currently licensed meningococcal polysaccharide vaccine, but persistence of serum antibody beyond 6 months after conjugate vaccination is unknown.

Objective: Determine persistence and the immunologic basis of protective activity of group C anticapsular antibodies in sera obtained 2-3 years after MC-4 vaccination.

Design: Group C antibody concentrations, bactericidal activity and passive protective activity were measured in sera from 48 children, ages 4-5 years, who had been immunized 2-3 years earlier with an MC-4 vaccine and from 47 children who had not been previously vaccinated.

Results: Serum antibody concentrations were higher in the vaccinated than the unvaccinated children (geometric means, 0.30 and 0.09 mug/mL, respectively, P < 0.0001). Bactericidal titers > or =1/4 (considered protective) were infrequent in both vaccinated and unvaccinated children (14.6 and 6.4%, respectively, P = 0.3). Passive protective activity against bacteremia in the infant rat model was more frequent in sera from vaccinated (37.5%) than sera from unvaccinated children (12.5%, P < 0.02). The proportion of sera with passive protective activity increased with increasing anticapsular antibody concentrations (P < 0.0001).

Interpretation: Serum group C antibody concentrations remained elevated for 2-3 years after MC-4 vaccination, and passive protective activity was more frequent in vaccinated than unvaccinated children. However, serum antibody concentrations in many vaccinated children were no longer sufficient to activate complement-mediated bacteriolysis in vitro or to confer passive protection against experimental group C disease.

FIGURE 1

A, Reverse cumulative distributions of anticapsular antibody concentrations in sera obtained 2–3 years after MC-4 vaccination administered at a mean age ± SD of 2.6 ± 0.5 years (N = 48; ——) and from unvaccinated children (N = 47; – – – –). B, Anticapsular antibody concentrations in relation to passive protective activity against group C meningococcal bacteremia in the infant rat model. Each circle represents the antibody concentration of an individual child. , Sera with passive protective activity (P); ○, sera that were not protective (NP). Horizontal bars represent the geometric mean antibody concentrations of the different groups.