Vaccines
Table 1: Total Cases of Serogroup C Disease, with the Incidence in the Year with the Highest Level of Disease in the First Eight European Countries to Introduce a Meningococcal C Conjugate Vaccine (derived from EU-IBIS data)
Belgium Germany Iceland Ireland
Netherlands Portugal Spain
England and Wales *Between 1999 and 2005.
1999 2000 2001 2002 2003 2004 2005 Population (millions) Year Introduced Highest Annual Incidence* 77
88 10
85 96 9
— 29 179 89
135 139 35 87
12 14
47
2 5
21
3 5
18
107 277 223 44 50
78 51
17 15
1 5 4
10.2
118 174 165 122 108 82.2 13
0.3 3.6
16 28
16.8 9.9
356 370 147 218 178 146 122 39.4 1082 797 348 184 106 65
51.8
2002 2006 2002 2000 2002 2006 2000 1999
1.8 0.2 3.7 3.9 1.6 0.8 0.9 2.1
Figure 1: Case Fatality Ratios by Age and Serogroup for all European Countries Reporting to EU-IBIS for which Outcome Data were Available, 2006
10 15 20 25 30
0 5
<1 year
BC 1–4
5–9 years years
10–14 years
15–19 years
20–24 years
25–44 years
W135
Serogroup C Meningococcal Conjugate Vaccines
The first serogroup C meningococcal conjugate (MenC) vaccine was licensed in the UK in September 1999 and was introduced from 1 November 1999.2
Prior to this, well-established, licensed
polysaccharide vaccines against meningococcal disease were already available as bivalent serogroup A and C and tetravalent A, C, W135 and Y preparations. Such plain polysaccharide vaccines are made from small sections of the polysaccharide capsule and invoke a T-cell-independent immune response in which antibody is produced through direct interaction with B lymphocytes. T-cell-independent responses are age-dependent, not generally occurring before 18 months of age, and do not induce immunologicl memory.8
Licensed polysaccharide vaccines were therefore poorly effective at protecting young children, who are at the highest risk of invasive meningococcal disease, and could not provide long-term protection when given at any age. In addition repeated use of polysaccharide vaccines has been shown to lead to antibody hyporesponsiveness, when an immune response of lower magnitude is elicited following a second or subsequent dose of vaccine as opposed to the initial dose.9 However, the clinical relevance of this is unknown and no increased risk of invasive disease has been shown to follow widespread use of polysaccharide vaccines.10
The polysaccharide vaccines also have only
a temporary impact on meningococcal colonisation or transmission and therefore limited ability to induce herd immunity in a population.11,12
130
45–64 years
Y
65+ years
These recognised limitations with plain polysaccharide vaccines and the concerning changes in serogroup C disease epidemiology from the mid-1990s helped to drive the development of new MenC vaccines. These vaccines use conjugation techniques that had already been successfully employed in vaccines against Haemophilus influenzae type b (Hib) disease and had led to good control in a number of countries.13–15
Conjugate vaccines
consist of capsular polysaccharides conjugated or joined to a carrier protein. This conjugation enhances the immunogenicity of the polysaccharide antigen because proteins are taken in by antigen-processing cells and processed to form peptides.16 The peptides are expressed on the cell surface with major histocompatibility complex class II molecules that are recognised by T lymphocytes. A T-cell-dependent response is thereby elicited, with the production of a full range of high-affinity antibodies and the production of memory B cells.
Clinical trials of MenC vaccines demonstrated their immunogenicity and safety in all age groups, including infants, generally with lower reactogenicity than other vaccines given at comparable ages.2,17–21 MenC vaccines were subsequently shown to prime for immune memory up to four years after completion of infant immunisation and were therefore expected to confer long-term protection against meningococcal C disease.22
Three MenC vaccines were licensed and used in the UK. The vaccines manufactured by Wyeth (now Pfizer) and Chiron (now Novartis) are conjugated to the altered diphtheria CRM197 protein, while the vaccine manufactured by Baxter is conjugated using a tetanus toxoid protein. Each vaccine was licensed and introduced at a different time and used in specific age groups.
The Introduction of Serogroup C Meningococcal Conjugate Vaccines On 1 November 1999, the UK became the first country in the world to introduce a MenC vaccine both into the routine infant schedule and as a staggered mass catch-up campaign for all children up to 18 years of age.2
From 2000 onwards, MenC vaccines were introduced to the routine childhood schedules in a number of other European countries and by October 2007 these comprised Belgium, Germany, Iceland, Ireland, The Netherlands, Portugal, and Spain. The total numbers of cases of serogroup C disease, with the incidence in the year with the highest level of disease in these first eight European countries, are summarised in Table 1. The vaccine was also introduced on a voluntary or selective basis from 2001 onwards in the Czech Republic, Greece, Hungary, Italy, Norway, Poland, Sweden and Switzerland.7
EUROPEAN INFECTIOUS DISEASE
Percentage
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