Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

In the Netherlands, the increase in MenC disease in 2000-2002 was the reason to implement the MenC conjugate vaccine into the Dutch immunisation programme (Table 2). In 2000, 105 patients (an annual incidence rate of 0.7 per 100.000 inhabitants of the Netherlands) with a culture-proven serogroup C meningococcal infection were reported and in 2001 this number increased to 276 patients (an annual incidence rate of 1.7 per 100.000 inhabitants of the Netherlands). In the Spring of 2002, just prior to the implementation of the MenC vaccine into the immunisation programme, a vaccination campaign was initiated including all children aged from 14 months up to and including 18 years was started. Subsequently, the MenC vaccine, i.e. a conjugated MenC vaccine with tetanus toxoid as carrier protein, was introduced for children at the age of 14 months into the immunisation programme of the Netherlands from September 2002 onwards.

During this vaccination campaign approximately 3.5 million vaccinations were given, which together with the vaccinations given prior to the campaign resulted in a vaccination rate of 94% of the target population. At present, the vaccination rate among children receiving a single MenC conjugate vaccine dose at the age of 14 months according to the Dutch immunisation programme has been reported to be as high as ≥ 95% (birth cohort 2007) [7].

In the Netherlands, surveillance of MenC disease is performed by a central laboratory that receives nation-wide meningococcal isolates from more than 90% of all cases with invasive meningococcal disease. Strikingly, since the introduction of MenC conjugate vaccine in the Netherlands there has been no report of any case of MenC disease among immunocompetent vaccinees (Table 2). In addition, the MenC disease incidence among non-vaccinees showed a clear reduction due to herd immunity. From 2004 onwards, a maximum of 2 cases of MenC disease per year occurred at the age < 1 year (all infant cases occurred at the age ≥ 6 months, < 1 year). Apparently, the routine childhood vaccination and the initial catch-up campaign resulted in a reduction of circulating serogroup C meningococci which in turn has led to a decreased transmission. It is important to note that replacement by meningococci with other serogroups, i.e. serogroup A, B, Y, W135, was not observed. On the contrary, the incidence of serogroup B meningococcal disease decreased from 1998 onwards and continued to decline since the introduction of the MenC conjugate vaccine in 2002 [5]. However, this is considered to be based on coincidence, since the MenC vaccine does not induce cross-reactive immunity to meningococcal serogroup B bacteria. This is confirmed by a study in the United Kingdom, whereby the prevalence of carriage of meningococci associated with serogroup B disease was unaffected by the introduction of the MenC conjugate vaccine [8]. As expected, in this latter study a decline in prevalence of carriage of serogroup C meningococci was reported from 1999, the year of introduction of MenC conjugate vaccine in UK. This finding was consistent with the observed herd immunity in the non-vaccinated teenage population in the UK [8].

Recently, MenC-specific immunity before and after implementation of the MenC conjugate vaccine in 2002 in the Netherlands has been analysed using two large cross-sectional serum banks each obtained from a nation-wide Dutch population [9]. These serum banks contain samples from participants 0-79 years of age that were collected in two cross-sectional serosurveillance studies performed in 1995/6 and 2006/7 [10, 11]. From these serum banks, polysaccharide specific IgG concentrations against serogroup C meningococci and functional antibody titers obtained with the SBA have been determined and described earlier [9]. Here we show the SBA titres from respectively 735 and 1220 serum samples before and after the introduction of the MenC conjugate vaccine (Table 3). These data illustrate that, more than 4 years after vaccination (serum bank 2006/7), the MenC-specific SBA titres were still remarkably high (SBA geomean titre (GMT) ≥ 8) in individuals who were vaccinated at the age of 5 year or older during the vaccination campaign (aged 9/10 years in 2006/7) (Table 3). A single MenC conjugate vaccine administration above 5 years of age seems to induce persistent protective SBA antibody levels, gradually increasing with age of vaccination. In contrast, MenC-specific SBA levels in serum samples from individuals that have been vaccinated against MenC disease at the age of 14 months, i.e. according to the Dutch routine immunisation programme, showed a rapid decline within a few years after vaccination. Apparently, high functional antibody levels against serogroup C meningococci persist longer in persons who were vaccinated at an age of 5 year or older [9].

These findings are consistent with results from a study in the United Kingdom, showing that 5 years after vaccination children vaccinated at an age of 10 years or older exhibited higher functional (SBA) antibody levels against serogroup C meningococci compared to younger children [12]. Although, at present SBA is the best correlate of protection for evaluating the immune response to meningococcal serogroup C vaccines, for long-term protection SBA levels alone may not be ideal [13]. A better predictor for long-term protection may be a combination of SBA levels with the number of MenC-specific memory B cells [14]. At present, failures of long-term protection in children immunised with a single dose of MenC conjugate vaccine at the second year of life have not been documented [3]. The question that thus remains is whether the existing antibody response and/or B cell memory response in the individuals vaccinated with a single dose at the age of 14 months will be strong enough to prevent disease in case of exposure to serogroup C meningococci at later ages. High SBA levels may be necessary, because meningococci have the potential of rapid multiplication leading to fast progression of MenC disease [15, 16]. This is probably why some countries (i.e. Austria and Switzerland) have implemented a booster dose at adolescent age in addition to the vaccine dose in the second year of life (Table 1). So far, no breakthroughs of MenC disease have occurred in immunocompetent vaccinated individuals in the Netherlands. This is most probably due to diminished circulation of serogroup C meningococci as a consequence of herd immunity induced by vaccination. On the other hand, it might be that all vaccinated individuals are protected, despite the low SBA levels in those who have been vaccinated at younger ages.