ReviewEffectiveness of meningococcal serogroup C vaccine programmes
Introduction
Bacterial meningitis is a life-threatening disease that is caused by bacterial infection of the meninges. Neisseria meningitidis is the most common cause of bacterial meningitis and a major cause of septicaemia [1], [2], [3]. In Europe, the US and other developed countries, meningococcal disease incidence is typically between 1 and 10 per 100,000 population, with occasional ‘hyperendemic’ periods of persistent disease caused by particular strains. The incidence of meningococcal disease is highest among infants; the rates drop after infancy but increase during adolescence and early adulthood.
There are 12 serogroups of N. meningitidis, defined on the basis of different immunochemical variants of the polysaccharide capsule that surrounds the bacteria but only six (A, B, C, W, X, Y) cause life-threatening disease [4]. While large meningococcal serogroup A outbreaks have been prevalent in Africa, serogroup B and C meningococci cause most disease in Europe, where most cases are sporadic, with small case clusters periodically occurring [5]. In 2008 (n = 4978) and in 2009 (n = 4637), a total number of 9615 cases of invasive meningococcal disease were reported in Europe with an overall notification rate of 0.99 per 100,000 population in 2008 and 0.92 in 2009 [6].
A major advance in meningococcal disease prevention has been the development of meningococcal glycoconjugate vaccines including meningococcal serogroup C (MenC) glyconjugate (MCC) vaccines. MCC vaccines were implemented to combat the increase in serogroup C disease due to the ST11 clonal complex which, before reaching the UK, had spread through Canada, Spain and the Czech Republic [7]. The UK was the first country to introduce MCC vaccination in 1999, incorporating MCC vaccines into the routine infant schedule at 2, 3 and 4 months of age. An extensive single-dose catch-up campaign was implemented for 1- to 18-year olds [7]. Other European countries, Australia and Canada followed suit and have all subsequently observed substantial reduction in MenC disease [8], [9], [10], [11], [12]. In addition to MCC vaccines, quadrivalent conjugate vaccines against serogroups A, C, Y, and W are available and recently, a four-component recombinant serogroup B vaccine has been licensed in Europe.
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Concepts of vaccination
Several underlying concepts of vaccination (summarized in Table 1) are important for fully understanding the impact of MCC vaccination programmes. Within medical communities in some territories there is a danger that the current low incidence of MCC disease may lead to a misconception that scheduled vaccination programmes can be halted or scaled back. This view is erroneous and there is a need to increase awareness of MCC vaccination and emphasize the importance of continued vaccination.
MCC vaccines: the clinical evidence
Commercially available vaccines that contain serogroup C comprise monovalent conjugate vaccines, quadrivalent conjugate vaccines, polysaccharide vaccines and a combination MenC-Haemophilus influenzae type b (Hib) conjugate vaccine. Their formulation, adjuvants used and antigenic content are summarized in Table 2.
Polysaccharide vaccines are effective in the short term but are not used in routine vaccination campaigns because they do not induce a T-cell-dependent immune response, and are
Toddler priming
In a study of toddlers (n = 226) aged 12–18 months, a single dose of the three licensed MCC conjugate vaccines resulted in a high SBA GMT and rates of SBA ≥8. NeisVac-C induced higher SBA GMTs and higher seroprotection rates, 1 month and 6 months after vaccination. Challenge with a plain AC polysaccharide vaccine demonstrated the induction of immunologic memory of all three vaccines. Again the NeisVac-C group reached a significantly higher SBA GMT [26].
In 2002, a single MCC (NeisVac-C)
Concluding remarks
A considerable body of evidence exists for the clinical effectiveness of MCC vaccines and the success of routine vaccination programmes. All of the available MCC vaccines, however, show significantly greater long-term effectiveness when administered to toddlers than to infants. Of the currently licensed MCC vaccines, NeisVac-C shows the greatest longevity of immune response. However, the protective antibody titre of all MCC vaccines has been found to drop within 18 months of vaccination,
Author disclosures
RB has performed contract research on behalf of Pubic Health England (formerly Health Protection Agency) that was funded by Pfizer, Novartis Vaccines, Baxter Bioscience, GlaxoSmithKline, Sanofi Pasteur, Alexion Pharmaceuticals Inc., Emergent Europe, and Merck. JAV has acted as a consultant for and received travel support from GlaxoSmithKline, and Sanofi Pasteur, and has undertaken contract research on behalf of the National Institute of Health Carlos III, Madrid, Spain, for GlaxoSmithKline,
Acknowledgments
This paper was supported by an educational grant from Baxter Healthcare. Representatives of Baxter Healthcare had no role in gathering, analysing, or interpreting the information presented. Editorial assistance was provided by Touch Medical Communications.
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