Meningococcal Serogroup C Conjugate Research Articles

Evaluation of Meningococcal Serogroup C Bactericidal Antibodies after Primary Vaccination: A Multicentre Study, Italy.

Here, we evaluated over time in different cohorts of children vaccinated against serogroup C Neisseria meningitidis, the presence of antibodies with neutralizing activity. A total of 348 sera samples of enrolled children by year since vaccination (<1 year- up to 5 years), starting from February 2016 to December 2017, were collected in three collaborating centers. Meningococcal serogroup C (MenC) antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA) following standard operating procedures. The cut-off of rSBA titer ≥ 8 is considered the correlate of protection. We observed a significantly declining of bactericidal rSBA titers by 23% every year, for every 1-year from vaccination (Adjusted PR = 0.77, 95% CI: 0.71–0.84). The proportions of children with bactericidal antibodies, immunized with the meningococcal serogroup C conjugate (MCC) vaccine, declined from 67.7% (95% CI: 48.6–83.3%) one year after vaccination, to 36.7% (95% CI: 19.9–56.1%) five years after vaccination (chi-square for linear trend, p < 0.001). Children vaccinated with the tetravalent meningococcal serogroup ACWY vaccine resulted in a high proportion of bactericidal rSBA MenC titer ≥ 1:8 (90.6%, 95% CI: 79.3–96.9%) after a mean time of seven months. Overall, the results provide some evidences on the evaluation of meningococcal serogroup C bactericidal antibodies after primary vaccination.

Diversity of meningococci associated with invasive meningococcal disease in the Republic of Ireland over a 19 year period, 1996-2015.

This study examined the capsular phenotype and genotype of invasive meningococcal disease (IMD)-associated Neisseria meningitidis recovered in the Republic of Ireland (RoI) between 1996 and 2015. This time period encompasses both pre- (when IMD was hyperendemic in the RoI) and post- meningococcal serogroup C conjugate (MCC) vaccine introduction. In total, 1327 isolates representing over one-third of all laboratory-confirmed cases of IMD diagnosed each epidemiological year (EY), were characterised. Serogroups B (menB) and C (menC) predominated throughout, although their relative abundance changed; with an initial increase in the proportion of menC in the late 1990s followed by their dramatic reduction post-MCC vaccine implementation and a concomitant dominance of menB, despite an overall decline in IMD incidence. While the increase in menC was associated with expansion of specific clonal-complexes (cc), cc11 and cc8; the dominance of menB was not. There was considerable variation in menB-associated cc with declines in cc41/44 and cc32, and increases in cc269 and cc461, contributing to a significant increase in the clonal diversity of menB isolates over the study. This increase in diversity was also displayed among the serosubtyping data, with significant declines in proportions of menB isolates expressing p1.4 and p1.15 antigens. These data highlight the changing diversity of IMD-associated meningococci since 1996 in the RoI and emphasise the need for on-going surveillance particularly in view of the recent introduction of a menB vaccine.

Immunogenicity and safety of a new hexavalent vaccine (DTaP5-IPV-HB-Hib) administered in a mixed primary series schedule with a pentavalent vaccine (DTaP5-IPV-Hib)

DTaP5-IPV-HB-Hib vaccine is a fully-liquid, combination hexavalent vaccine. This phase III, open-label, multicentre study conducted in Spain, evaluated the immune response to all DTaP5-IPV-HB-Hib antigens when the vaccine was used in a mixed hexa/penta/hexa primary series. Infants (who had received one dose of hepatitis B vaccine at birth) received a mixed schedule including DTaP5-IPV-HB-Hib (PRP-OMP conjugate) at 2 and 6months of age, DTaP5-IPV-Hib at 4months, meningococcal serogroup C conjugate (MCC) vaccine at 2 and 4months, and routine rotavirus and pneumococcal vaccination. One month post-dose 3 of the mixed schedule, response rates were considered acceptable if the lower bound of the two-sided 95% confidence interval around the post-vaccination response rate was >90% for hepatitis B and >80% for Haemophilus influenzae type b (Hib). Secondary immunogenicity objectives included description of the antibody response to all hexavalent antigens one month after completion of the mixed schedule, and to MCC antigen one month after the second MCC dose. The safety profile after each dose of study vaccine was described. Of 385 healthy infants enrolled, 384 completed the study. The primary objective was achieved for both hepatitis B and Hib; the lower bound of the 2-sided 95% CI of the response rates (97.2% and 99.0%, respectively) were greater than the pre-specified acceptability thresholds. One month post-dose 3 of the mixed schedule, all participants were seroprotected against diphtheria, tetanus and polio. The mixed schedule induced a robust immune response to all hexavalent antigens. The co-administration of the hexavalent vaccine in a mixed schedule with MCC vaccine did not reduce the immune response to vaccine antigens. Vaccines were well tolerated. In conclusion, the acceptability of response rates against Hib and hepatitis B were demonstrated one month post-dose 3 of the mixed schedule; robust immune responses against all other hexavalent antigens were observed.clinicaltrial.gov: NCT01839188; EudraCT: 2012-004221-25

What Would be the Best Schedule for Prevention of Meningococcal Disease in All Ages? The UK Experience.

Meningococcal disease is a major global public health problem, and vaccination is the optimal means of prevention. Meningococcal vaccination programmes have significantly evolved, for example, in the UK, since their introduction in 1999. The UK, the first country to introduce meningococcal serogroup C conjugate (MCC) vaccination, commenced this in 1999 with a primary infant series at 2, 3 and 4 months of age, together with a catch-up campaign of a single dose for children aged 1-18 years. Subsequent changes to the schedule have occurred in response to increasing knowledge about how MCC vaccines work, together with improved knowledge of meningococcal transmission. Firstly, in 2006, the schedule was refined from a three-dose to a two-dose priming schedule with the addition of a booster in the second year of life. This was followed by a further change in 2013, when the number of priming doses was further reduced to a single priming dose along with a booster maintained at 12 months of age and the introduction of an adolescent MCC booster dose. This in 2015 was changed from monovalent serogroup C to quadrivalent A, C, W and Y in response to an outbreak of serogroup W.

Vacuna conjugada frente al meningococo C: impacto del programa de vacunación y efectividad a largo plazo en Navarra, 2000-2014

BackgroundSince 2000, when the meningococcal serogroupC conjugate vaccine (MenCC) was introduced in the childhood immunization schedule in Spain, several changes in the schedule and catch-up campaigns have been performed. We aim to estimate the impact and effectiveness of this vaccine in Navarra up to 2014. MethodsThe impact of the vaccination program was analysed by comparing incidence, mortality and lethality rates of disease before (1995-1999) and after (2004-2014) the introduction of the MenCC. Vaccine effectiveness was estimated using the screening method (Farrington) and the indirect cohort method (Broome). Data on cases were obtained from the active surveillance of meningococcal disease. ResultsDuring 1995-1999 the mean annual incidence of meningococcalC disease was 1.32 per 100,000, and 7.18 per 100,000 in children younger than 15years. The fall of meningococcalC disease incidence was significant in cohorts targeted for vaccination from the beginning and progressive in the general population. No cases were reported between 2011 and 2014. The estimated vaccine effectiveness was 96% by the screening method, and 99% by the indirect cohort method. ConclusionThe MenCC vaccination program has been successful in decreasing the incidence rate of serogroupC meningococcal disease in Navarra, and schedule changes have maintained high vaccine effectiveness throughout the study period.

Primary Meningococcal-C Conjunctivitis in a Vaccinated Child

Meningococcal conjunctivitis is classified into primary (direct inoculation of the bacteria into the palpebral conjunctiva from an exogenous source) and secondary (as an unusual complication of systemic meningococcal disease). Primary meningococcal conjunctivitis (PMC) is an uncommon cause of bacterial conjunctivitis. It is important to establish an early diagnosis in view of the potential for invasive meningococcal disease. Vaccination with meningococcal serogroup C conjugate (MCC) vaccines reduces the carriage of serogroup C meningococci and protects against invasive infection. We report a case of a meningococcal C conjunctivitis in a vaccinated child.

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

BackgroundAntibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels.MethodsMeasurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier.ResultsThe number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster.ConclusionsCirculating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC.

Present situation and new perspectives for vaccination against Neisseria meningitidis in Tuscany, Central Italy.

In Italy one third of bacterial meningitis are caused by Neisseria meningitidis. In March 2005, the Regional Health Authority of Tuscany included the meningococcal serogroup C conjugate (MCC) vaccine in the recommended vaccination program with a schedule of three doses to all newborns at 3, 5 and 13 months of age (from 2008 amended to a single dose at 13 months) and a single catch-up dose until age 6. To evaluate the impact of the current national and regional immunization strategies against N. meningitidis and to highlight new perspectives for meningococcal disease prevention with the existing tetravalent meningococcal vaccine (ACWY) and with the future incoming meningococcal B vaccines. Meningitis incidence rates in Italy and in Tuscany were calculated for the period 1994-2011 and 2005-2011,respectively. Immunization coverage with MCC vaccine in Tuscany and vaccination status of meningitis cases were reported. Literature review on meningococcal conjugate vaccine use and recommendation was performed. A decrease in incidence rates of meningococcal meningitis was observed in all age groups involved in the immunization campaign. Immunization coverage with MCC increased progressively year by year in Tuscany. A herd immunity effect was measured in unvaccinated age groups. Since 2006 no cases of invasive meningococcal C infection in vaccinated subjects were observed in Tuscany. Implementation of MCC vaccination in Tuscany was effective in preventing meningococcal C disease, confirming the effectiveness of the vaccine. A new tetravalent (ACWY) conjugate vaccine is now available and its use in all Italian Regions should be considered.

Age-Related Immunity to Meningococcal Serogroup C Vaccination: An Increase in the Persistence of IgG2 Correlates with a Decrease in the Avidity of IgG

BackgroundAll children and adolescents between 1 and 19 years of age in The Netherlands received a single meningococcal serogroup C conjugate (MenCC) vaccine in 2002. During follow-up 4–5 years later, the persistence of MenC polysaccharide-specific IgG was found to be dependent on age of vaccination with higher IgG levels in the oldest immunized age categories.Methods and FindingsTwo cross-sectional population-based serum banks, collected in 1995/1996 and in 2006/2007, were used for this study. We measured MenC polysaccharide-specific IgM, the IgG1 and IgG2 subclasses and determined the avidity of the IgG antibodies. We report that the age-related persistence of IgG after immunization with the MenCC vaccine seemed to result from an increase of IgG2 levels with age, while IgG1 levels remained stable throughout the different age-cohorts. Furthermore, an age-related increase in IgM levels was observed, correlating with the persistence of IgG antibodies with age. It is noteworthy that the increase in IgG2 correlated with a reduced IgG-avidity with age.ConclusionThese date indicate that the classical characteristics of a T-cell-dependent antibody response as elicited by protein based vaccines might not be completely applicable when conjugate vaccines are administered to older children and adolescents up to 18 years of age. The response elicited by the MenCC vaccine seemed to be more a mixture of both T cell dependent and T cell independent responses in terms of humoral immunological characteristics.

WITHDRAWN: Conjugate vaccines for preventing meningococcal C meningitis and septicaemia.

Meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection. To assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia. We searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library 2005, issue 3); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population-based observational studies about effectiveness were included. Two authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them. The studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important. The MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically effective.

Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

Functional T-Cell Deficiency in Adolescents Who Experience Serogroup C Meningococcal Disease despite Receiving the Meningococcal Serogroup C Conjugate Vaccine

Some individuals have experienced meningococcal disease despite receiving the meningococcal serogroup C conjugate (MCC) vaccine in adolescence. We sought to determine whether this is due to subclinical functional B- or T-cell immunodeficiency. Of 53 vaccine failures identified by enhanced surveillance of England and Wales from 1999 to 2004, 15 received MCC vaccine in adolescence, 9 of whom were recruited 2 to 6 years following convalescence from meningococcal disease. Their peripheral blood mononuclear cells (PBMCs) were incubated with polyclonal activators designed to mimic T-cell-independent B-cell stimulation by bacterial polysaccharides and the T-cell stimulation provided by the protein component of the conjugate vaccine. Subsequent proliferation and activation of T and B lymphocytes were measured, along with T-cell help to B cells. Compared to age-, sex-, geographically, and ethnicity-matched controls, CD4 T-cell proliferation rates in response to both anti-CD3 (T-cell receptor [TCR]) stimulation and anti-CD3 in the presence of B cells activated through anti-IgD conjugated to dextran (alpha-delta-dex) were lower in PBMCs derived from vaccine failures (P = 0.044 and P = 0.029, respectively). There was reduced CD4 cell activation of the patient cells compared to controls following stimulation by CD3 (P = 0.048). B-cell activation during incubation of PBMCs with the T-cell stimuli, anti-CD3 (P = 0.044), or anti-CD3 plus anti-CD28 (P = 0.018) was relatively impaired in patients. Anti-tetanus toxoid IgG concentrations were lower in the vaccine failure group (P = 0.0385). There was a relative defect of T-cell responsiveness to T-cell-dependent antigen stimulation in MCC vaccine failures, which was manifested in reduced T-cell help to B cells.

Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults

In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults ( n = 21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC polysaccharide vaccine. Blood samples were collected prior to immunization and at 6 additional time points, from 3 to 25 days post-immunization. Secondary immunization resulted in 5–10-fold higher IgG titers compared to the primary immunization group, 25 days post-immunization. Prior to the secondary immunization, but 5 years after the first immunization, protective bactericidal antibodies and levels of MenC-specific IgG and IgM were still present. Furthermore, IgG antibodies present before secondary immunization were of higher avidity compared to antibodies produced one month after primary immunization. In addition, secondary immunization with nonconjugated MenC polysaccharide seemed to induce a higher IgG2 response compared to MenCC immunization. The kinetics of the observed secondary immune responses were not really faster than the observed primary responses. However, the rate of increase in antibodies seemed faster than the primary responses, representing a booster response. As the course of infection by Neisseria meningitidis can be very rapid, these data support the idea that sustainment of high antibody levels induced by MenCC are important for immediate protection.

Absence of Neisseria meningitidis Serogroup C-Specific Antibodies during the First Year of Life in The Netherlands: an Age Group at Risk?

In The Netherlands, a single meningococcal serogroup C conjugate (MenCC) vaccination is administered to children at the age of 14 months. Here, we report the levels of MenC polysaccharide-specific antibodies in children at birth and at 3, 11, and 12 months of age and the presence of functional antibodies at 11 months of age, before infants receive their MenCC immunization. We observed a rapid decline in polysaccharide-specific antibodies after birth and no induction of naturally elicited polysaccharide-specific antibodies. Furthermore, at 11 months of age, no bactericidal antibodies are observed. These data indicate that these infants may be at risk in the period prior to MenCC immunization, if Neisseria meningitidis serogroup C starts to (re)circulate.

Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programs

Effective vaccines provide direct protection to immunized individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and thereby lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunized individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK, targeting teenagers for immunization was crucial in maximizing indirect effects, as most meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunization strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new meningococcal vaccines.

Antibody persistence in UK pre-school children following primary series with an acellular pertussis-containing pentavalent vaccine given concomitantly with meningococcal group C conjugate vaccine, and response to a booster dose of an acellular pertussis-containing quadrivalent vaccine

This open-label, randomised, controlled study examined antibody persistence following infant vaccination at 2, 3 and 4 months of age with either an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Haemophilus influenzae type b (DT 5aP-IPV-Hib; Pediacel ®) or a whole-cell pertussis (DTwP//Hib + oral poliomyelitis vaccine [OPV]) combination vaccine, given concomitantly with meningococcal serogroup C conjugate (MCC) vaccine, followed by a Hib booster at approximately 15 months of age. Immune responses were sustained to 3.5–4.5 years of age for all antigens contained in Pediacel. Administration of an acellular pertussis-containing quadrivalent pre-school booster (Td 5ap-IPV; Repevax ®), with or without measles, mumps and rubella (M-M-R™II) vaccine, induced robust antibody responses indicative of protection, regardless of the vaccine used for the primary series. Reactogenicity of Repevax was acceptable and consistent with previous experience.

Expanding prevention of invasive meningococcal disease

Invasive meningococcal disease due to serogroups A, C, Y and W-135 is a serious, vaccine-preventable, worldwide public-health problem. Despite early treatment and advances in medical care, morbidity and mortality rates have essentially remained unchanged. Monovalent, meningococcal serogroup C conjugate (MCC) vaccines against Neisseria meningitidis are effective in children under 2 years of age. MCC vaccines also provide indirect protection to unvaccinated individuals through herd immunity by reducing nasopharyngeal carriage in immunized individuals. Evidence from MCC and other conjugate vaccine initiatives supports immunization initiated as a late infancy/toddler program for prevention of disease caused by serogroups C, Y and W-135. We propose that a meningococcal vaccination program focused on later infancy and the early second year of life should be the preferred approach, providing comparable effectiveness to an early-infant strategy with fewer overall doses and greater cost–effectiveness.

Seroprevalence of Antibodies against Serogroup C Meningococci in England in the Postvaccination Era

The United Kingdom introduced meningococcal serogroup C conjugate (MCC) vaccines in 1999, resulting in substantial declines in serogroup C disease and carriage. Here, we measured the age-specific prevalence of serum bactericidal antibodies (SBA) to Neisseria meningitidis serogroup C and immunoglobulin G (IgG) concentrations to serogroups A, C, W-135, and Y in 2,673 serum samples collected in England between 2000 and 2004. We compared the seroprevalence of SBA titers of > or =8 in the postvaccination era with results from an earlier prevaccination study conducted using the same methods. We found that the percentages of individuals with protective SBA titers were higher in 2000 to 2004 in all of the age groups targeted for MCC vaccination. In the postvaccine era, the prevalence of protective titers was high (75%) in children who had recently been offered routine immunization, but this fell to 36% more than 18 months after scheduled immunization. In the cohorts targeted in the catch-up campaign, the percentage achieving SBA titers of > or =8 was higher in children offered the vaccine at ages 5 to 17 years than in children offered the vaccine at ages 1 to 4 years. The geometric mean concentration (GMC) IgG for serogroup C followed a similar pattern, corresponding to the age at and time since scheduled MCC vaccination. Serogroup-specific IgG GMCs for W-135 and Y were low and showed little variation by age. Serogroup A IgG GMCs were higher, possibly reflecting exposure to cross-reacting antigens. Although the incidence of serogroup C disease remains low due to persisting herd effects, population antibody levels to serogroup C meningococci should be monitored so that potentially susceptible age groups can be identified should herd immunity wane.

Impact of Meningococcal Serogroup C Conjugate Vaccines on Carriage and Herd Immunity

In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.

Cochrane review: Conjugate vaccines for preventing meningococcal C meningitis and septicaemia

AbstractBackgroundMeningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins (‘conjugating’), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection.ObjectivesTo assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia.Search strategyWe searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies.Selection criteriaRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population‐based observational studies about effectiveness were included.Data collection and analysisTwo authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them.Main resultsThe studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo‐responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important.Authors' conclusionsThe MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically effective.Plain language summaryTraditional meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease (caused by Neisseria meningitidis), but do not produce an immune response in infants less than two years of ageThis limitation can be overcome by linking C polysaccharide to carrier proteins (‘conjugating’), to create meningococcal serogroup C conjugate (MCC) vaccines. This review looks at MCC vaccines to protect young children against Serogroup C disease. Trials found that MCC induces an immune response against serogroup C in all age groups, but especially younger children for whom the immune response is greater than that of the traditional MPLS. It appears to be safe. Clinical efficacy of MCC could not be assessed from randomised controlled clinical trials (there were none). However, weaker evidence from observational studies showed a decrease in meningococcal C disease and meningococcal C carriage in countries where vaccines have been widely used.