A rapid and simple method for the simultaneous quantitation of serum immunoglobulin G (IgG) antibodies specific for Neisseria meningitidis serogroups A, C, Y, and W-135 was developed and evaluated. Four bead sets were generated, each conjugated with one of the meningococcal capsular polysaccharides (A, C, Y, or W-135) and serologically assessed by the use of antimeningococcal international reference sera. Cross-reactivity studies demonstrated no inhibition between monoplex and multiplex assays, and the assay was linear over a 24-fold serum dilution range. Inhibition studies demonstrated that the assay is specific, with <25% heterologous inhibition occurring. The assay was also found to have low intra-and interassay variations and limits of detection <650 pg/ml. A comparison of the meningococcal bead assay with the standardized meningococcal enzyme-linked immunosorbent assay showed a good correlation between the IgG concentrations obtained by each assay. The tetraplex assay has the potential to be an important addition to the serologic evaluation of meningococcal capsular polysaccharide conjugate vaccines.

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Two-year-old children were vaccinated with 1 dose of meningococcal A/C conjugate (MACC) or meningococcal A/C polysaccharide (MACP) vaccine. Meningococcal serogroup A (MenA)-specific IgG geometric mean avidity indices (GMAIs) increased 1 month after vaccination with MACC (GMAI, 210; 95% confidence interval [CI], 140-300) and MACP (GMAI, 190; 95% CI, 120-310). One year after vaccination, the GMAI of the MACP-vaccinated cohort decreased to 130 (95%, CI 100-170), but a constant GMAI was maintained in the MACCvaccinated cohort (210; 95% CI, 140-300), despite declining MenA-specific IgG antibody levels.Meningococcal A/C polysaccharide (MACP) vaccines are effective for short-term control of meningococcal serogroup A (MenA) disease [1] and have been used extensively for controlling outbreaks and epidemics. MenA polysaccharide, unlike meningococcal serogroup C (MenC) polysaccharide, is immunogenic in children !2 years old [2]. MACP vaccines fail to induce immunological memory, and antibody levels progressively decline to preimmunization levels within 3 years after vaccination [3]. Immunological hyporesponsiveness-that is, impaired serum antibody responses to revaccination 6-12 months later-has been documented for MenA [4,5]. The clinical relevance of this phenomenon is unclear; revaccination is not believed to cause disadvantages for vaccinated individuals, compared with unvaccinated individuals, but it raises questions about the value of revaccination as a control measure.Conjugate vaccine technology circumvents the low immunogenicity of pure polysaccharide vaccines by inducing a T celldependent immune response, rather than a T cell-independent response. Studies of meningococcal A/C conjugate (MACC) vaccine have demonstrated these vaccines to be safe and immunogenic in children [4,6,7]. The development of immunological memory may be demonstrated by the measurement of antibody avidity indices (AIs) and has been used recently to study both meningococcal A and C conjugate vaccines [8][9][10].The primary aim of the present study was to investigate MACC and MACP vaccine responses by the use of AIs. The sample size chosen was to investigate trends in the AIs between MACP-and MACC-vaccinated cohorts.Methods. The study population consisted of 49 children, 2-3 years old, selected from a larger study of 207 children recruited from participating general practices in Oxfordshire, United Kingdom, who were randomly assigned to receive either MACC or MACP vaccine. A subset of children was selected randomly from each study cohort for AI analysis: 25 from the MACC cohort and 24 from the MACP cohort.The experimental MACC vaccine used was a 0.5-mL dose containing 4 mg each of MenA and MenC polysaccharide and 48 mg of diphtheria toxoid (polysaccharide-to-protein weight ratio, 1:4) formulated into 10 mM sodium phosphate-buffered physiological saline and a licensed MACP vaccine containing 50 mg each of MenA and MenC polysaccharides (Mengivac; Pasteur Merieux). The polysaccharides used to prepare the MACC vaccine were the same as those used t...