In the 2009 survey, results were available for 1,174 samples, of which 415 (35%; 95% CI, 33 to 38%) had evidence of seroprotection (shown by attaining putatively protective SBA titers of ≥8).
The data were first categorized into the same age-bands used in our two previous similarly designed surveys of samples taken prior to MCC introduction (in 1996 to 1999) and shortly after introduction of MCC (in 2000 to 2004) (21
) (). This showed that protective levels were similar in those aged 0 to 4 years in 2009 compared with 2000 to 2004, but strikingly, the secondary peak of high levels seen in adolescent age groups in 2000 to 2004 (representing those eligible for catch-up vaccination from primary school age forwards) has shifted into the older age groups. Thus, levels in those aged 5 to 9 and 10 to 14 years in 2009 are lower than in 2000 to 2004, although still higher than in the prevaccine study. Among the adults, seroprotection levels had seemed to decline following vaccine introduction. The latest survey, however, shows seroprotection levels that are very similar to those of the prevaccine era.
Fig 1 Seroprotection against serogroup C meningococci measured by proportions with serum bactericidal antibody (SBA) titers of ≥8. Shown is a comparison of current levels (2009) with the periods before (1996 to 1999) and shortly after (2000 to 2004) (more ...)
In further analysis according to vaccine schedule (), cohorts that were eligible for single-dose catch-up vaccination at the outset of the MCC program in 1999 and 2000 showed declining levels of antibody in all age groups. The percentage decline in GMTs from 2000 to 2004 to 2009 was highest in the cohorts with the highest initial levels, with the GMTs declining from 89.7 (95% CI, 66 to 122) (n = 394) to 28.3 (95% CI, 19 to 42) (n = 101) in those eligible for vaccination at secondary school, from 104.2 (95% CI, 74 to 147) (n = 266) to 27.5 (95% CI, 18 to 43) (n = 132) in those eligible for primary school vaccination, and from 12.6 (95% CI, 10 to 16) (n = 392) to 7.2 (95% CI, 5 to 11) (n = 165) in those eligible for preschool vaccination (). Seroprotection levels remained much higher in those who were eligible for vaccination at primary or secondary school age (born between 1982 and 1994 and approximately between 6 and 18 years old at the time of the catch-up campaign) compared to those eligible for toddler/preschool single-dose catch-up vaccination (born in 1995 to 1997 and 3 to 5 years old during that period). Protection was especially low in children born in 1998, who were eligible for the single catch-up vaccine dose in early 2000 and were approximately 1 year old then.
Proportions of samples with protective levels of antibody by birth cohort and vaccination schedule
Those 4 to 10 years old at sampling in 2009 (born in 1999 to 2005) had eligibility for routine vaccination with infant doses only (before the addition of a booster to the schedule in 2006). Only about a quarter of these subjects had protective antibody levels (26.0%; 95% CI, 20 to 33%).
Children born between 2006 and 2008 (approximately 1 to 3 years old when sampled), who were eligible for the current routine schedule of two infant primary doses plus a booster at age 12 months, also had only modest seroprotection, with less than one-third showing a protective SBA titer (31.6%; 95% CI, 24 to 40%). The youngest groups (infants born in 2009, up to 11 months old at sampling) showed notable seroprotection levels, but as they were either yet to commence or to complete their vaccination under the current schedule, they were not readily comparable to other groups.
GMTs followed a similar pattern to that described for proportions of seroprotection ( and ), across all of the vaccinated and the older unvaccinated age groups. GMT levels remained relatively high for those targeted for catch-up vaccination as older children than those who were eligible for the routine schedules. Similar to the seroprotection proportions, high GMTs in infants of 2000 to 2004 fell sharply—as seen in the comparator 5- to 9-year-old band of 2009.
Geometric mean titer (GMT) of serum bactericidal antibody (SBA) against group C meningococci. Shown are current levels (2009) compared with the period shortly after vaccine introduction (2000 to 2004).
Between the ages of 1 and 3 years, antibody levels were similar in children eligible for vaccination according to both the old schedule (doses at 2, 3, and 4 months) and the current schedule (3, 4, and 12 months). At the ages of 1, 2, and 3 years, respectively, GMT measurements in the 2000-to-2004 survey were 13.7 (95% CI, 9 to 20) (n = 138), 7.5 (95% CI, 5 to 11) (n = 109), and 5.7 (95% CI, 4 to 8) (n = 83), compared to 13.1 (95% CI, 7 to 25) (n = 49), 6.1 (95% CI, 3 to 11) (n = 51), and 3.3 (95% CI, 2 to 5) (n = 33) in 2009.
Within a year and around 2 years after vaccination, antibody levels were comparable to or higher than those in children eligible for a single-dose catch-up in the second year of life (without having been primed as infants) and those eligible for the booster at age 12 months. In the 1998 birth cohort (eligible for single-dose catch-up in 2000 and sampled in 2001), the GMT was 4.7 (95% CI, 2 to 9) (n = 40). This compared with 6.1 (95% CI, 3 to 11) (n = 51) in the 2007 birth cohort (eligible for the 12-month booster in 2008 and sampled in 2009). Around 2 years after vaccination, the levels in the catch-up group (born in 1998, eligible for a single-dose catch-up in 2000, and sampled in 2002) were higher (13.4; 95% CI, 7 to 26; n = 43) than in those eligible for the current routine schedule (born in 2006, eligible for the 12-month booster in 2007, and sampled in 2009) (3.3; 95% CI, 2 to 5; n = 33).