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.
It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one-or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n ؍ 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of >8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of >8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.In November 1999, the United Kingdom introduced universal meningococcal C conjugate (MCC) vaccination at 2, 3, and 4 months of age, on the basis of safety and immunogenicity studies (15). A prelicensure study in 83 infants in the United Kingdom (18) who were given one of the three candidate MCC vaccines, a tetanus toxoid conjugate (MCC-TT) (14), at 2, 3, and 4 months of age demonstrated that the vaccine was highly immunogenic after a single dose at 2 months of age, with all infants achieving a putative protective antibody titer of Ն8 (bactericidal antibody levels in serum were measured with baby rabbit complement [rSBA]) (1a, 3). There was a further significant increase in antibody levels after a second dose of MCC-TT vaccine but no further increase after the third dose at 4 months of age. Antibody levels fell by 14 months of age, but booster antibody responses to meningococcal C polysaccharide and MCC vaccines provided evidence of successful priming for immunologic memory after the full course of three doses (18).The excellent response to this MCC-TT vaccine among infants at 2 months of age and the modest response to the third dose of vaccine raise the possibility that a one-or two-dose schedule in infants may be sufficient to provide protection from meningococcal C disease. Demonstration of priming for immune memory by the one-or two-dose schedules suggests that these regims could also provide long-term protection. This could be assessed by examining antibody responses to meningococcal C polysaccharide vaccination in the second year of life since children do not normally respond to polysaccharide ...
An immunization campaign with meningococcal ACYW135 polysaccharide vaccine was conducted in 2003 by the Saudi Arabian Ministry of Health and included a study to evaluate the immune responses in children under 5 years of age in the Al Qassim region of Saudi Arabia. Children who were >24 months old were given one dose of tetravalent polysaccharide vaccine, while younger children were given two doses with an interval of 2 to 3 months. Blood samples were collected prevaccination and 1 month after the second dose for children younger than 24 months old and 1 month after the single dose for older children. Serogroup-specific antibody responses were determined by serum bactericidal antibody (SBA) assays and a tetraplex immunoglobulin G (IgG) bead assay. Significant increases in the proportions of individuals who were >24 months old with SBA titers of >8 were observed pre-to postvaccination for all serogroups. Age-dependent increases in the percentage of individuals with SBA titers of >8 1 month postvaccination were observed for each serogroup. Age-dependent increases in postvaccination IgG levels were observed for serogroup A (menA), serogroup W135 (menW), and serogroup Y (menY) but not for serogroup C (menC). Two doses of tetravalent polysaccharide vaccine in individuals who were <18 months old were poorly immunogenic for menC, menW, and menY. However, for menA, 42% of the children who were 18 months old were putatively protected with SBA titers of >8. A high percentage of subjects who were >2 years of age were putatively protected for menA; a similar level was observed for menY for children who were 4 years of age but not for younger children. However, for menC and menW poor levels of putative protection were still evident at 4 years of age.
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