Prevalence of Serum Bactericidal Antibody to Serogroup C Neisseria meningitidis in England a Decade after Vaccine Introduction

Immunisation Department, Health Protection Agency, Colindale, London, United Kingdom.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.47). 05/2012; 19(8):1126-30. DOI: 10.1128/CVI.05655-11
Source: PubMed


Serogroup C meningococcal disease incidence and carriage declined rapidly in the United Kingdom after infant serogroup C conjugate vaccination was introduced in 1999, with catch-up vaccination for children under 18 years. Antibody levels and effectiveness waned quickly in children vaccinated at 2, 3, and 4 months of age. Therefore, in 2006, the current revised schedule of doses at 3, 4, and 12 months was introduced. This study assessed age-specific protection in 2009 compared with data from historical prevaccination and early postvaccination studies. Rabbit complement serum bactericidal antibody (SBA) was measured in anonymously banked serum samples collected in England in 2009 (n = 1,174), taking titers of ≥ 8 as protective. Age-stratified proportions of SBA titers that were ≥ 8 and geometric mean titers were compared. SBA titers varied markedly by birth cohort and time since vaccination. Overall, 35% of samples (95% confidence interval [CI], 33 to 38%) had titers that were ≥ 8. Only in cohorts eligible for catch-up vaccination did the majority of individuals have protective antibody levels. Antibody levels were higher in children eligible for vaccination at primary and secondary school ages, compared to those eligible below the age of 5 years. In those eligible for completed vaccination under the current schedule, protective levels were very modest and there was no evidence of superiority to cohorts that were eligible for the previous schedule. This supports a need for older childhood or adolescent booster vaccination in those previously eligible for vaccination during the infant, toddler, or preschool periods, to maintain direct protection and potentially enhance population immunity.

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    • "The incidence of IMD in the US is currently very low, and evidence to demonstrate herd protection based on a reduction in IMD cases in unvaccinated groups is therefore much more challenging. In response to evidence of waning immunity to MenC in adolescents[65], in 2013 the UK moved one dose of MCC from infants to adolescents 14-15 years of age[66]. In a more recent development in response to an increase in severe disease due to an epidemic serogroup W clone in England and Wales, the UK Joint Committee on Vaccination and Immunisation recommends adolescent vaccination with MenACWY-TT to commence in August 2015[8]. "
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    ABSTRACT: Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable.
    No preview · Article · Dec 2015 · Expert Review of Vaccines
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    • "Investigation of the immunogenicity of the MenC vaccine component was complicated as trial subjects were laboratory workers, who had previously received meningococcal vaccination. Consequently, 79% of subjects had baseline MenC rSBA titres ≥ 8 which is at least double, than previously reported in the UK general population ≥ 25 years of age in 2009 [23]. At enrolment, subjects with prior vaccination against MenC had been vaccinated with MCC vaccine either through the MCC catch-up campaign during 1999 to 2000 [2], a MCC staff trial [24] and/or through the Occupational Health Department with multivalent polysaccharide vaccines. "
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    ABSTRACT: Background Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. Methods A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. Results At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 μg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. Conclusions Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.
    Full-text · Article · Jul 2014 · Journal of Occupational Medicine and Toxicology
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    • "As with the earlier Hib vaccine, the UK MCC vaccination introduction was dramatically successful, with rapid reductions in meningococcal serogroup C disease in vaccinated and unvaccinated individuals [76] that have been sustained for more than a decade [77] (figure 2). This success stimulated the introduction of MCC vaccines in a number of other countries and provides the prospect of serogroup C meningococcal disease control [78–80]. "
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    ABSTRACT: The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.
    Full-text · Article · Aug 2013 · Philosophical Transactions of The Royal Society B Biological Sciences
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