We recruited a total of 999 participants from 22 educational institutions (median number of participants per school/campus 13, range 1-174). As outlined in table 1, we evaluated immunogenicity results for 987 participants. The mean age of these participants was 14.8 (SD 2.02) years, and the mean time since immunisation was 4.9 (SD 0.34) years. Table 2 shows further demographic details.
Table 2 Demographics and vaccine received for participants included in immunogenicity analysis. Values are numbers (percentages) unless stated otherwise
Antibody persistence in Menjugate recipients according to age at enrolment
Of the 987 participants, 708 (72%) had received Menjugate (mean age 15.0 (SD 2.04) years). Mean time since immunisation was 4.9 years and tended to be slightly longer in older age bands (4.7 years in 11-13 year olds, 5.0 years in 14-16 year olds, and 5.3 years in 17-20 year olds). Serum bactericidal antibody titres of at least 1:8 were shown by 83.3% (95% confidence interval 80.4% to 86.0%) of Menjugate recipients (table 3). When analysed according to age band, the geometric mean bactericidal antibody titres, geometric mean IgG concentrations, and percentage of participants with bactericidal antibody titres of at least 1:8 and at least 1:128 were all significantly lower in 11-13 year old Menjugate recipients than in 14-16 year olds and 17-20 year olds.
Table 3 Markers of immunogenicity for Menjugate recipients. Values in parentheses are 95% confidence intervals
Antibody persistence in Menjugate recipients according to age at immunisation
In order to assess more directly the influence of age on the immune response, we analysed the above measures of immunogenicity according to year of immunisation (fig 1, tables 4 and 5). Whereas the geometric mean bactericidal antibody titres were relatively consistent for participants immunised at age 6-9 years, we saw a marked increase in geometric mean bactericidal antibody titres in those immunised at age 10 (table 4). This was then again relatively consistent for those immunised at older ages. We saw similar, although less marked, trends in seroprotection levels. We also saw a trend to increasing geometric mean serogroup C meningococcal IgG concentrations with increasing age at immunisation (table 4), with a less clear demarcation in antibody concentration between years 9 and 10 than was seen with the geometric mean bactericidal antibody titres.
Fig 1Meningococcal serogroup C (MenC) specific serum bactericidal antibody geometric mean titre (SBA GMT) after Menjugate immunisation, by age of immunisation
Table 4 Multiple regression analysis for meningococcal serogroup C specific serum bactericidal antibody geometric mean titres and IgG geometric mean concentrations after immunisation with Menjugate at ages 6-7, 8, 9, 10, and 11 years, compared with immunisation (more ...)
Table 5 Logistic regression analysis for percentage of participants achieving serum bactericidal antibody titres ≥1:128 after immunisation with Menjugate at ages 6-7, 8, 9, 10, and 11 years, compared with immunisation at 12-15 years
We further analysed this trend by multiple regression analysis, adjusting for sex, time since immunisation, the batch number of Menjugate received, and the clustering effect of school/campus attended. As shown in table 4, even after adjustment for these factors, participants immunised at age 6-7, 8, or 9 years of age had significantly lower geometric mean bactericidal antibody titres than those immunised at ages 12-15 years. By contrast, we found no significant difference in the geometric mean bactericidal antibody titres between participants immunised at 10 and 11 years and those immunised at 12-15 years, again supporting an increment in serogroup C meningococcal bactericidal antibodies in those immunised with Menjugate at 10 years of age or above, independent of sex, time since immunisation, batch number received, or clustering effects of school/campus attended. We saw the same increment when we analysed the percentage of participants achieving bactericidal antibody titres of at least 1:128 by logistic regression (again correcting as above) (table 5).
We considered receipt of the “school leaver” combined diphtheria and tetanus vaccine as another possible confounding factor. For those Menjugate recipients for whom we had data, only 20 of 66 aged 9 years at serogroup C meningococcal immunisation had received a booster dose of diphtheria and tetanus vaccine before enrolment, compared with 100 of 108 children aged 10 years at time of immunisation. The close relation between age at immunisation and likelihood of receipt of the school leaver vaccine before enrolment meant that we could not analyse the relation between the receipt of this vaccine and the geometric mean bactericidal antibody titres and geometric mean IgG concentrations independent of age at immunisation.
Antibody persistence in all serogroup C meningococcal vaccine recipients according to age at enrolment
We extended analysis of immunogenicity to all 987 participants with confirmed history of receipt of any of the three serogroup C meningococcal vaccines. This showed a meningococcal serogroup C bactericidal antibody titre of at least 1:8 in 830 participants (84.1%, 81.6% to 86.3%). Table 6 shows further measures of immunogenicity for all ages and according to age band (irrespective of vaccine received).
Table 6 Percentage with serogroup C meningococcal specific serum bactericidal antibody (SBA) titres ≥1:8 and ≥1:128, SBA geometric mean titres (GMT), and IgG geometric mean concentrations (GMCs) of all participants included in immunogenicity (more ...)
In further analysis for impact of age at enrolment on these measures in non-Menjugate recipients, we saw a non-significant tendency to lower geometric mean bactericidal antibody titres in 11-13 year olds than in 14-16 year olds and 17-20 year olds for Meningitec recipients and to lower geometric mean bactericidal antibody titres in 11-13 year olds than 14-16 year olds for NeisVac-C recipients (fig 2).
Fig 2Meningococcal serogroup C (MenC) serum bactericidal antibody geometric mean titre (SBA GMT) after receipt of MenC vaccine, by age band at blood sampling and vaccine received. No participants in 17-20 year age band received NeisVac-C
We also analysed the geometric mean titres of serogroup C meningococcal bactericidal antibody and geometric mean concentrations of IgG for each vaccine separately within each age band (figs 2 and 3). For 11-13 year olds we saw a tendency for Menjugate recipients to have a lower geometric mean bactericidal antibody titres (124, 95% confidence interval 91 to 170) than recipients of NeisVac-C (256, 151 to 433) or Meningitec (243, 120 to 493). However, analysis of the impact of vaccine received on geometric mean titres of serogroup C meningococcal bactericidal antibody within this age group revealed no significant differences (P=0.1 for Menjugate compared with NeisVac-C and P=0.3 for Menjugate compared with Meningitec). This trend was less obvious when we compared the percentage of participants with bactericidal antibody titres of at least 1:128 (fig 4) or those with bactericidal antibody titres of at least 1:8 (data not shown) or geometric mean IgG concentrations (fig 3).
Fig 3Meningococcal serogroup C (MenC) specific IgG geometric mean concentration (GMC) after receipt of MenC vaccine, by age band at blood sampling and vaccine received. No participants in 17-20 year age band received NeisVac-C
Fig 4Percentage of participants with serum bactericidal antibody (SBA) titres ≥1:128 after meningococcal serogroup C (MenC) immunisation, by age band and vaccine received. No participants in 17-20 year age band received NeisVac-C