A Short Review of Serogroup C Meningococcal Conjugate Vaccines
of subjects with protective levels of antibody was between 22 and 43 %, depending on the priming MenC vaccine used, inicating that additional booster doses of MCC vaccine may be required in the future to maintain protective antibody levels.33
Serogroup Replacement and Capsule Switching Prior to the introduction of the MenC vaccine, concerns were raised that the vaccine might exert selection pressure on meningococcal organisms and lead to capsule switching, which results from meningococcal clones changing the type of capsule they express.46
If
capsular switching occurred, an increase in common serogroup C serosubtypes would be expected in other serogroups. This has been carefully monitored and the emergence of such serosubtypes has not been apparent. The data available on ST have shown that serosubtype 2a is the best routinely available phenotypic marker for ST-11, the major serogroup C hypervirulent lineage. Serogroup B:2a incidence has therefore been carefully monitored and there has been no change following the introduction of the MenC vaccine.32,34
Replacement disease was also considered a possible outcome of immunisation against serogroup C; this would result in an increase in the incidence of another serogroup or serogroups with the potential to reduce the overall impact of the programme. There has been no evidence to suggest an increase in serogroup B disease in European countries that have adopted a MenC programme (see Figure 4).34 The overall incidence of meningococcal disease has fallen since the introduction of the MenC vaccine in England and Wales (see Figure 4). No individual serogroup has shown a sustained increase during the post-vaccine period. A short-term increase in the number of cases of serogroup W135 occurred in 2001–2002, and the number of serogroup Y cases doubled from 29 in 20072008 to 58 in 2008–2009. It is unlikely that either change was due to the impact of conjugate vaccination, but both underline the importance of continued surveillance.
Vaccine Safety
Studies of MenC vaccines under trial conditions have found them to be safe and generally less reactogenic than other childhood vaccines given at similar ages, with no serious adverse reactions identified.2,17,18,20,21 No association between local reactogenicity and the presence of pre-vaccination diphtheria or tetanus antibody following immunisation with either the DT/Td or MCC vaccines has been found.47
A formal safety
review on completion of the MenC immunisation campaign in the UK covered the period from introduction to 28 February 2001, during which around 18 million doses of MenC vaccines were distributed and around 13,000 spontaneous suspected adverse drug reaction reports submitted.48
The safety profiles of the first two vaccines used in the campaign (Meningitec™ and Menjugate™) were reported to be broadly similar, no new serious effects were identified and the balance of risks and benefits for MCC vaccines was considered overwhelmingly favourable.
1. World Health Organization, Epidemics of meningococcal disease, African meningitis belt, 2001, Weekly Epidemiological Record, 2001;37:282–8.
2. Miller E, Salisbury D, Ramsay M, Planning, registration and implementation of an immunization campaign against meningococcal serogroup C disease in the UK: a success story, Vaccine, 2001;20(Suppl. 1):S58–67.
3. Kremastinou J, Tzanakaki G, Kansouzidou A, et al., Recent emergence of serogroup C disease in Greece, FEMS Immunol Med Microbiol, 1999;23:49–55.
4. Berron S, De La Fuente L, Martin E, et al., Increasing incidence of meningococcal disease in Spain associated with a new variant of serogroup C,
Studies to investigate postulated links between the MenC vaccine and an increased risk of purpura, relapse of nephritic syndrome,49 encephalitis and/or convulsion have been undertaken. These did not identify a causal association between the MenC vaccine and any of these conditions.50–52
of viral or invasive bacterial infections in the 90 days after co-administration of MenC with the combined measles, mumps and rubella vaccine.53
The Future of Serogroup C Meningococcal Conjugate and Other Vaccines
Most countries do not currently recommend a MenC booster dose during adolescence, but the need for this has been advocated.54 Modelling does not currently support the need for a further booster55 in countries such as England and Wales. However, in the future it is possible that a later dose for those entering adolescence, in whom disease and carriage was previously highest, may be considered. Higher antibody levels are required to prevent carriage than to protect against disease and, as a better antibody response is generated at older ages, an adolescent booster could potentially have more impact on transmission.56
Continued high-quality post-licensure
surveillance and modelling are key to inform these and other decisions about vaccine programmes.34
In countries that include MenC vaccine in their infant schedule, with the current low levels of disease it may be possible to maintain control with fewer doses of vaccine. For example, the use of a single dose of MenC in infancy followed by a booster at disease 12 months has the potential to sustain the excellent level of control by optimising the effect of indirect protection. Studies of NeisVac-C™ (MenC conjugated to tetanus toxoid) have found that antibody levels after a single dose in infancy are comparable to those obtained in two-dose schedules.57,58
Priming for immunological
memory was also demonstrated after either one or two doses. The ability of reduced schedules of conjugate vaccination to provide high levels of population protection bodes well for the use of conjugate serogroup A vaccines in Africa, where campaign approaches may be able to reach larger numbers of individuals than routine programmes.
Vaccines based on conserved subcapsular antigens have been developed and are nearing licensure. Such vaccines could offer simultaneous protection against specific strains of all meningococcal serogroups, including serogroup B. If these vaccines do become widely available, it is possible that a continuing need for a serogroup-C-specific vaccine may be reduced in the childhood immunisation programme. However, major issues to consider will be whether such vaccines can protect against carriage and therefore sustain herd immunity and whether they can provide sufficient coverage against a wide range of strains for all serogroups. n
Eur J Clin Microbiol Infect Dis, 1998;17:85–9.
5. Cafferkey M, Murphy K, Fitzgerald M, et al., Epidemiology of meningococcal disease in Ireland: a report on laboratory confirmed cases, July 1999 to June 2000, EPI-INSIGHT, 2000;1:2–3.
6. EU-IBIS Network, Surveillance network for invasive Neisseria meningitidis in Europe – 1999 and 2000. Commission of the European Communities. Available at:
www.euibis.org/ documents/19992000_meningo.pdf (accessed 1 September 2011).
7. EU-IBIS Network, Invasive Neisseria meningitidis in Europe 2003/2004. Health Protection Agency, London 2006. Available at:
www.euibis.org
8. Pollard AJ, Goldblatt D, Immune response and host- pathogen interactions. In: Pollard AJ, Maiden MCJ (eds), Meningococcal vaccines: Methods and protocols, Totowa, New Jersey: Humana Press, 2001;23–40.
9. Borrow R, Joseph H, Andrews N, et al., Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults, Vaccine, 2000;19:1129–32.
10. De Wals P, De Serres G, Niyonsenga T, Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec, JAMA, 2001;85:177–81.
11. Hassan-King MKA, Wall RA, Greenwood BM, Meningococcal carriage, meningococcal disease and vaccination, J Infect, 1988;16:55–9.
There was no significant increase in the risk
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