Long-term protection in children with meningococcal C conjugate vaccination: lessons learned

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Abstract
Owing to an increase in group C disease, extensive prelicensure studies have been funded by both the UK Department of Health and vaccine manufacturers. These demonstrated the safety and immunogenicity of three candidate meningococcal group C conjugate (MCC) vaccines (two conjugated to CRM197 and one to tetanus toxoid) in the targeted age groups. Induction of immunological memory in infants and young children was also demonstrated by either a low dose of polysaccharide challenge following primary immunization with MCC or by an increase in avidity indices post-primary to pre-challenge. Immune memory after infant immunization persisted to at least 4 years of age, although antibody persistence in this age group was poor. MCC vaccine was introduced into the UK routine immunization schedule at 2, 3 and 4 months of age in 1999, with a catch-up as a single dose to all children aged 1–18 years with two doses for infants aged 5–11 months. The number of group C cases fell rapidly in the targeted age groups and early analyzes showed high vaccine effectiveness in all age groups together with significant herd immunity. However, when effectiveness was measured again more than 1 year after vaccination, there was a significant decline in all age groups, most marked in infants vaccinated in the routine infant immunization program, for whom there was no demonstrable efficacy after only 1 year and then in toddlers for whom efficacy declined to 61% (95% confidence interval: -327–94) from 88% (95% confidence interval: 65–96) in the first year. However, good disease control was maintained in the UK with only low numbers of vaccine failures. The assumption that immune memory was predictive of long-term protection is incorrect, at least after vaccination in infancy. Persistence of antibody and herd immunity may be more relevant for long-term disease control.