Maintenance of immune response throughout childhood following serogroup c meningococcal conjugate vaccination in early childhood

Abstract

The objectives of this study were to evaluate the kinetics of antibody decline through childhood in a longitudinal study of a single cohort following serogroup C meningococcal (MenC) vaccine immunization in early childhood and to calculate the proportion of 11 to 13 year olds with protective levels of bactericidal antibody 10 years after immunization. United Kingdom children aged 11 to 13 years in 2010 who had previously taken part in a longitudinal study at the Oxford Vaccine Group had blood samples drawn between 2001 and 2010. Sera from each time point were analyzed for the MenC serum bactericidal antibody titer using a baby rabbit complement (rSBA) assay. The median age at MenC immunization was 21 months (range, 1 year 3 months to 3 years 9 months). The MenC rSBA geometric mean titer (GMT) at age 3.5 to 5 years was 8.0 (95% confidence interval, 6.5 to 9.9; n ‫؍‬ 287). By age 11.5 to 13.5 years, the rSBA GMT had declined to 3.3 (2.5 to 4.4; n ‫؍‬ 98). The percentage of children with rSBA titers of >1:8 (the threshold for protection) also declined from 38% (35% to 41%) to 15% (12% to 19%). We concluded that MenC rSBA titers wane rapidly following vaccination in early childhood and continue to decline into the second decade of life. Since nasopharyngeal colonization in adolescents probably provides the major reservoir for MenC in the population, declining immunity in this cohort is of concern. Sustaining high levels of antibody through booster vaccination in this cohort is likely necessary to avoid a resurgence of disease in the decade ahead.

Serum bactericidal antibody assays – The role of complement in infection and immunity

“…Only in catch-up cohorts, in other words in those older than infants, were protective levels evident. A similar observation had been made by the Oxford Vaccine Group in a 10 year follow-up study of individuals vaccinated with MCC vaccines at a median age of 21 months using rabbit complement [88]. The percentage of children with rSBA titres of >8 had declined from 38% (range 35-41%) to 15% (range 12-19%).…”

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age

“…19,29 Others have, however, estimated a slower annual 23% decline (95% CI: [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] in odds of protection after Meningitec vaccination at age 13-45 months. 30 This study also provided long-term (12-14 years) postprimary antibody persistence data in individuals primed at preschool age. Approximately one-third to one-half of participants (depending on primary vaccine) were still putatively seroprotected, with significantly higher preboost MenC titers in those primed with MCC-TT.…”

“…The age at primary vaccination may be crucial for the differential effect, as 5-year persistence after priming in older age cohorts (6-15 years) did not significantly differ between TT-conjugated and CRM-conjugated MCC vaccine groups. 29 Previous studies of postprimary persistence in teenagers did not compare different vaccine carrier proteins and involved cohorts that were primed at older ages (≥9 years) 17,20 or younger (1-3 years) 30 (and therefore with different immunologic backgrounds) than our participants. Similar to the postbooster analysis, there are limitations in our primary persistence data as only a modest proportion of the original trial cohort could be included in this study, given the practical challenges of recruiting teenage participants from a previous childhood study of over a decade earlier.…”

Long-term seroprotection after an adolescent booster meningococcal serogroup C vaccination

“…The majority of children starting school have SBA below the level which has been correlated with protection 8. By 11.5–13.5 years of age, only 15% of children immunised at 1–4 years of age with a single dose of glycoconjugate vaccine had protective antibody levels (SBA ≥8, assayed using rabbit complement) 9. This waning of SBA titres may adversely affect the direct protection of adolescents, and also threatens the herd protection achieved by reduced nasopharyngeal carriage acquisition rates of MenC following immunisation with glycoconjugate vaccines, as the age groups most likely to carry and transmit meningococci are adolescents and young adults 10–12.…”