This is the first study to describe, within a single cohort of children, the kinetics of the decline in bactericidal antibody until early adolescence following immunization with a MenC conjugate vaccine at 1 to 3 years of age. In our cohort, only 15% of 11- to 13-year-old children had protective levels of antibody, slightly higher than the 6.9% of 10 to 14 year olds with rSBA titers of ≥1:8 in the prevaccine era (samples taken between 1996 and 1999) (23
), and the rate of decline in antibody titers was independent of the age at vaccination. Since the children in our study had been immunized between 1 and 3 years of age, these results may underestimate the decline in bactericidal antibody in children immunized in infancy. Borrow et al. found that doubling the time from vaccination resulted in a two-thirds reduction in MenC SBA titers. This decay was similar following 3 doses of MenC vaccine at 2, 3, and 4 months of age compared to after a two-dose course of MenC followed by a 12-month booster dose of a Hib-MenC vaccine (3
), similar to the current United Kingdom immunization schedule. Importantly, the current study shows that this pattern of antibody waning is maintained over at least 10 years.
A rapid decline in the incidence of MenC disease was noted in the United Kingdom following institution of routine MenC vaccination of children in 1999, and between 1999 and 2009 there was a 99% reduction in the number of confirmed cases (6
). This was probably mostly due to the immunization of adolescents and young adults in the nationwide campaign of 1999 to 2000 (2
). Carriage of N. meningitidis
is low in the first few years of life, rising sharply during adolescence to a peak of 10 to 35% in 20 to 24 year olds (8
). Cross-sectional studies have demonstrated that a small proportion of meningococcal isolates are serogroup C (14
); however, this may underestimate the proportion of young people who are exposed to the organism due to rapid transmission, short duration of carriage, and reacquisition over time. Adequate immunity in adolescents and young adults prevents nasopharyngeal carriage of MenC and transmission of the organism within the population, establishing herd immunity (14
). Interpretation of mathematical models of herd immunity effects following the national immunization campaign in the United Kingdom has suggested that this could last for several years (6
). However, in the absence of continued vaccination of adolescents, persistence of antibody following infant or early childhood immunization may not be sufficient to maintain this in the long term. Our results demonstrate that the current cohorts of children entering adolescence are unlikely to have protective levels of antibody, and thus, herd immunity may also start to wane. Furthermore, children in this study mainly received a MenC-CRM197
conjugated vaccine, which was found to be the least immunogenic of the three licensed MenC conjugate vaccines (3
). It was in wide use during the national immunization campaign, so these results could be generalized to a large group of United Kingdom adolescents.
Waning effectiveness has been demonstrated beyond 1 year after infant immunization with MenC conjugate vaccines and is associated with a fall in SBA titers over the same period (6
). Decreases in SBA titers over time have also been demonstrated in other age groups, with more marked waning in children immunized at younger ages (3
) and much better persistence demonstrated following immunization of older children and adolescents (19
). A study evaluating MenC SBA titers in 11 to 20 year olds in the United Kingdom, approximately 5 years after immunization with a conjugate MenC vaccine, demonstrated that higher SBA titers were observed in children who had been vaccinated at age 10 years or older than in children who had been vaccinated at a younger age (21
). Similar findings were observed in Greece, where 5 years after vaccination with a MenC conjugate vaccine, SBA titers in most children immunized at less than 6 years of age were below the threshold for protection, whereas protective levels were seen in the majority of children immunized at over 10 years of age (19
Our results demonstrate an overall waning of antibody levels throughout childhood and into early adolescence. It is thus unlikely that exposure to cross-reactive antigens (such as Escherichia coli
]) could boost levels of MenC bactericidal antibody in older children and adolescents. The evidence suggests that age-dependent differences noted between young children and adolescents are probably due to a better immune response with less rapid decline in antibody levels caused by immunological maturity in older children and adolescents. Our GMT results () suggest that the greatest decline in antibody titers occurs in the first year after vaccination. No clear decline is noted between 2003 (5 years of age) and 2004 to 2005 (7 years of age); however, there is then a persistent decline in antibody titers over the subsequent 5 years of the study. The same results viewed on a log10
scale (data not presented) show a more linear decay over time, and the regression analysis to determine the rate of change over time was performed with this assumption.
In the United States, young adolescents have been targeted for immunization with the quadrivalent serogroup A, C, W-135, and Y meningococcal (MenACWY) conjugate vaccine since 2005. However, even in this age group, waning of effectiveness has been observed (preliminary data), and the Advisory Committee on Immunization Practices in the United States now recommends that a booster dose of vaccine be administered to adolescents at 16 years of age, following the first dose given at around 12 years (9
). The routine childhood immunization schedule in Canada has also recently been modified to include a booster dose of vaccine (either a MenC or a MenACWY conjugate vaccine) at 12 years of age, following infant immunization (16
). The results of this study provide evidence to support these changes and suggest that similar changes may be necessary in the United Kingdom. However, these results should be considered in conjunction with those obtained from nasopharyngeal carriage studies and vaccine effectiveness data.
MenC bactericidal antibody titers wane rapidly following vaccination in early childhood, without evidence of natural boosting of antibody levels through exposure to cross-reactive antigens. In the United Kingdom, consideration should be given to a routine adolescent booster of MenC conjugate vaccine to protect this cohort of children who are entering the potentially high-risk period of adolescence. Such a booster will help to maintain herd immunity through ongoing prevention of nasopharyngeal carriage.