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The coadministration of the combined meningococcal serogroup C conjugate (MCC)/ Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and Haemophilus influenzae type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM 197 (Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of ≥8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years.

In response to the rising incidence of Haemophilus influenzae type b (Hib) disease in the United Kingdom, a national campaign to give a booster dose of single-antigen Hib conjugate vaccine to children aged 6 months to 4 years was undertaken in 2003. Children ( n = 386) eligible for Hib vaccine in the campaign were recruited. Hib antibody concentrations were measured before boost and at 1 month, 6 months, 1 year, and 2 years after boost and were analyzed according to children's ages at booster dose and whether a Hib combination vaccine containing acellular pertussis (aP) or whole-cell pertussis (wP) components was given in infancy. The geometric mean antibody concentrations (GMCs) before the booster declined as the time since primary immunization increased ( P < 0.001), and GMCs were threefold higher in recipients of wP-Hib than aP-Hib combination vaccines ( P < 0.001). GMCs 1 month after the booster increased with age ( P < 0.001) as follows: 6 to 11 months; 30 μg/ml (95% confidence interval [CI], 22 to 40); 12 to 17 months, 68 μg/ml (95% CI, 38 to 124); and 2 to 4 years, 182 μg/ml (151 to 220), with no difference according to the type of priming vaccine received. Antibody levels declined after the booster, but 2 years later, GMCs were more than 1.0 μg/ml for all age groups. By extrapolating data for the decline in antibody levels, we found the GMCs 4 years after boosting were predicted to be 0.6, 1.4, and 2.6 μg/ml for those boosted at 6 to 11 months, 12 to 17 months, and 2 to 4 years, respectively, with levels of at least 0.15 μg/ml in about 90% of individuals. A booster dose of Hib vaccine given after the first year of life should provide long-lasting protection.

Changes in the immunoglobulin G1 (IgG1)/IgG2 ratio following vaccination can indicate the activation of cellular control mechanisms typical of a T-cell-dependent response. We examined IgG subclass ratios in 17 healthy adults (26 to 55 years of age) before and 4 to 6 weeks following immunization with a quadrivalent meningococcal-polysaccharide diphtheria toxoid conjugate vaccine against serogroups A, C, Y, and W135. Serologic responses were determined by serum bactericidal antibody assay and serogroup-specific IgG, IgG1, and IgG2 enzyme-linked immunosorbent assay. Prevaccination serogroup A-specific IgG1/IgG2 ratios were

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naïve adults and prior MACP vaccinees. Laboratory staff (n= 113) were recruited; 73 were naïve to meningococcal vaccination, and 40 had previously received ≥1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of ≥8 or ≥128 were similar (P> 0.46); >94% of subjects achieved titers of ≥128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naïve (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P= 0.02), and similarly at 6 months (P< 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naïve and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.