Review
Meningococcal polysaccharide–protein conjugate vaccines

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Summary

It is now 5 years since the UK became the first country to introduce the serogroup C meningococcal polysaccharide–protein conjugate vaccines (MenC) into its routine immunisation schedule. This article reviews the global use of MenC with particular reference to the range of immunisation strategies used internationally. To date, concerns that MenC may result in an increase in meningococcal disease due to non-C serogroups have not been realised. The vaccine has proved to be highly safe and effective; however, concerns have arisen regarding the duration of vaccine effectiveness. Although booster doses of MenC may potentially extend the duration of protection offered by the vaccine, there are, as yet, no studies assessing this option. Clinical trials are underway to assess new combination conjugate vaccines (containing A, C, Y, and W polysaccharides), and it is probable that these more broadly protective vaccines will become available in the near future.

Section snippets

Serogroup C Neisseria meningitidis

Despite occasional epidemics in sub-Saharan Africa,1, 2 serogroup C meningococcal disease has generally been associated with endemic disease. In the late 1980s, however, a hyperinvasive clone bearing the meningococcal C polysaccharide capsule emerged in Ontario, Canada.3 Serologically, this clone was typed as C2a:P1·5,2,4 and was identified by multilocus enzyme electrophoresis (MLEE) as ET15, a member of the ET37 complex (panel 1).

The ET15 clone was first identified in 1986, at which time it

Development of MenC

The limitations of meningococcal serogroup C polysaccharide vaccines are well documented and thought to arise because the antigenic structure of the polysaccharide structure is not recognised by the T-cell receptor (T-independent antigen). Although immunogenic in most adults,29, 30 polysaccharide vaccines do not induce immunological memory and are poorly immunogenic in infants less than 2 years old.31

The improved immunogenicity of polysaccharide capsules when conjugated to protein carriers,

MenC efficacy/effectiveness

Although the above trials demonstrated promising immunogenicity, there was still no formal efficacy data for MenC. However, the combination of rising ST11 disease rates in the UK, safety and immunogenicity data, and the availability of in vitro correlates of protection provided support for the introduction of MenC. This introduction was facilitated by the political will engendered by public and media concern over the threat of meningococcal infection, and in October 1999 the UK became the first

MenC immunisation campaigns

Although the combination of factors that led to the introduction of MenC in the UK was unique, the impact of vaccine introduction on meningococcal disease rates in other countries and the cost-effectiveness of MenC programmes could now be deduced and introduction elsewhere has followed.

Ireland was the next country to introduce routine MenC immunisation, combining a mass immunisation campaign with incorporation into their routine 2, 4, and 6 month schedule in 2000.73 Similar campaigns were

Capsule switching

Capsule switching, the change in the association of a particular clone from one capsular polysaccharide to a different meningococcal polysaccharide, is well described in Neisseria meningitidis.88, 89 Indeed in the 1960s and 1970s the ST11 clone predominantly expressed serogroup B, before changing, apparently spontaneously, to serogroup C.90 Similarly during the ST11 serogroup C outbreaks in Canada, ST11 serogroup B isolates were reported91 and both serogroup B and W135 ST11 strains have been

The future of meningococcal prevention

Despite the effectiveness of the MenC vaccine campaign, only a portion of the worldwide meningococcal disease burden can be addressed by its use. In view of the difficulties in producing a serogroup B meningococcal (MenB) vaccine,117 attention has focused on the development of conjugate vaccines providing the possibility of protecting against serogroup A, C, Y, and W135 meningococci (MenACYW).118 This vaccine offers the potential for addressing epidemic meningococcal disease in sub-Saharan

Search strategy and selection criteria

Data for this review were identified by searches of MEDLINE, references from relevant articles, and the reports of the health agencies of the relevant countries. Search terms were “meningococcal”, “serogroup C”, “vaccination”, “immunisation”, “prevention”, and “conjugate”. Only English language papers were reviewed, with the exception of papers reporting epidemiological data from non-English speaking countries if English language alternatives were not available.

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