Meningococcal C Conjugate Vaccine Research Articles

Relation between the immunization rate by the meningococcal C-conjugate vaccine (MncC) and the Covid-19 pandemic in the population aged up to 1 year.

Relation between the immunization rate by the meningococcal C-conjugate vaccine (MncC) and the Covid-19 pandemic in the population aged up to 1 year.

Impact of meningococcal C conjugate vaccine on incidence of invasive meningococcal disease in an 18-year time series in Brazil and in distinct Brazilian regions.

To evaluate the impact of meningococcal C conjugate (MCC) vaccine in Brazil. Ecological study assessing all invasive meningococcal disease (IMD) and meningococcal C disease (MenC) cases reported in all age groups, from 2001 to 2019. MCC was implemented in 2010. Data were collected on the DATASUS platform. Joinpoint regression was performed to assess the annual percent change (APC) of the incidence rate. Invasive meningococcal disease incidence decreased in all Brazilian regions from 2001 onwards, without apparent additional reduction attributable to MCC vaccine in the North, Northeast and South. The higher and statistically significant APC reduction in all age groups, in the North and South, and in children <5years, in the Northeast, occurred between 2001 and 2011 (-15.4%), 2004 and 2012 (-14.4%), and 2001 and 2013 (-10.3%), respectively, before MCC vaccine implementation. Annual incidence of MenC in children under 5years significantly fell in the North (-6.8%; 2011-2018), Southeast (-40.6%; 2010-2015) and Midwest (-48.6%; 2010-2014), which may be attributable to MCC implementation. Invasive meningococcal disease and MenC behaved differently after MCC vaccine implementation in Brazil during this 18-year time-series analysis. This suggests that the control of IMD should be based on multiple public health care measures and considered on a regional basis.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES:To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC).METHODS:HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits.RESULTS:The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells.CONCLUSION:The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Systematic literature review of the impact and effectiveness of monovalent meningococcal C conjugated vaccines when used in routine immunization programs

BackgroundMonovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed.MethodsWe conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017.ResultsForty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3–4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules.ConclusionsMCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.

The epidemiological and clinical profile of meningococcal disease in a Public Secondary Hospital, São Paulo, Brazil

Introduction: Meningococcal meningitis is a widespread cause of community-acquired bacterial meningitis in children. In Brazil, meningococcal infection is endemic and usually strikes young individuals with clinical manifestations that may range from transient fever and bacteremia to fulminant disease, progressing over a matter of hours to death. The meningococcal C conjugate vaccine (MCC) was introduced in the Brazilian National Immunization Program in November 2010, scheduled at three and five months, with a booster dose at 12–15 months of age and an additional catch-up program targeting adolescents. In 2009 and 2010, notification …

A Comparison of Pyrogen Detection Tests in the Quality Control of Meningococcal Conjugate Vaccines: The Applicability of the Monocyte Activation Test

The meningococcal C conjugate vaccine (MenCC) is an interesting model with which to test the efficacy of the Monocyte Activation Test (MAT) as an alternative method of pyrogen testing in the quality control of vaccines. The MenCC that has been produced by Bio-Manguinhos in Brazil is in the final development stage, and, as recommended in the guidelines for MenCC production, its pyrogen content must be determined by using the Limulus Amoebocyte Lysate (LAL) assay and the Rabbit Pyrogen Test (RPT). This represents an ideal opportunity to compare LAL and RPT data with data obtained by using a MAT system with cryopreserved whole blood and IL-6/IL-1β as marker readouts. In order to assess the compatibility of the MAT with MenCC, endotoxin and non-endotoxin pyrogen content was quantified by using MenCC samples spiked with lipopolysaccharide (LPS), lipoteichoic acid or zymosan standards. The presence of the aluminium-based adjuvant interfered with the MAT, increasing the readout of IL-1β in LPS-spiked MenCC batches. This infringed the product-specific validation criteria of the test, and led to IL-6 being chosen as the more suitable marker readout. No pyrogenic contaminants were identified in the MenCC batches tested, demonstrating consistency among the different systems (MAT, RPT and the LAL assay). In conclusion, the introduction of the MAT during MenCC development could contribute to the elimination of animal tests post-licensing, ensuring human protection based on an effective non-animal based method of quality control.

Impact of meningococcal C conjugate vaccination programs with and without catch-up campaigns in adolescents: Lessons learned from Bahia, Brazil

ABSTRACTThe significant increase in the incidence rates and ongoing outbreaks of serogroup C meningococcal (MenC) disease, associated with the sequence type-103 complex, motivated the incorporation of the meningococcal C conjugate (MCC) vaccine in the routine immunization program in the State of Bahia, Brazil in early 2010, targeting children younger than 5 years of age. In its capital, Salvador, the program also included a catch-up campaign for individuals 10–24 years of age. We performed an observational, ecological study, analyzing data collected from 2007 to 2015, to compare the impact of these two immunization strategies on meningococcal disease incidence and mortality rates.In Salvador, following the vaccination program, a dramatic early impact on MenC disease and mortality rates could be observed, with significant reductions in incidence rates of MenC disease in all age groups, including individuals that were too old to have been vaccinated, indicating the presence of herd protection. Compared to the pre-vaccine period, a virtual disappearance of MenC disease was observed in 2015. However, in the state of Bahia (excluding the city of Salvador), no herd protection could be observed, with significant impact only among vaccine-eligible children within 5 years of introduction of the MCC vaccination program.These results highlight the importance of catch-up campaigns, including adolescents and young adults, to induce herd protection compared to immunization strategies restricted to infants and young children. This information is crucial for identifying optimal immunization policies and future strategies, focused on adolescents, to optimize the impact of MCC vaccination programs.

Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis mortality among children under five years of age in Brazil

ABSTRACTThe 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12–15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12–15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0–23 months and 2–4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0–23 months and 2–4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012–2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319) for children aged 0–23 months and 99 (95%CI 56–144) for those aged 2–4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.

Impact of meningococcal C conjugate vaccination four years after introduction of routine childhood immunization in Brazil

BackgroundRoutine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12–15months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program. MethodsWe performed an ecological quasi-experimental design from 2008 to 2014 using a deterministic linkage between the National Notification and the National Reference Laboratory databases for meningitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post-vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of São Paulo. ResultsA total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged <12months and no second incident peak was observed for adolescents. For Brazil, MenC rates were reduced by 67.2% (95%CI 43.0–91.4%) for infants <12months of age, 92.0% (77.3–106.8%) for the age-group 12–23months, and 64.6% (24.6–104.5%) for children aged 2–4years. For children 5–9years old, MenC rates reduced 19.2% (9.5–28.9%). Overall, 955 MenC cases were averted in Brazil in individuals aged <40years after MCC vaccination. Results from São Paulo State, mirror the patterns seen in Brazil. ConclusionAfter four years of infants and toddlers vaccination start, MenC invasive disease reduced in the target population. This investigation provide a robust baseline to ascertain how much the upcoming catch-up dose in 12–13years of age will accelerate the decrease in MenC incidence rates among youths in Brazil.

The epidemiology of invasive meningococcal disease in EU/EEA countries, 2004–2014

BackgroundInvasive meningococcal disease (IMD) is a major cause of bacterial meningitis and septicaemia although infection by some serogroups may be prevented through vaccination. We aimed to describe the epidemiology of IMD in EU/EEA countries during 2004–2014 to monitor serogroup- and age-specific trends, and compare country trends by the period of meningococcal C conjugate (MCC) vaccine introduction. MethodsWe analysed IMD surveillance data by age, gender, serogroup, country and outcome. We estimated the percentage change in annual notification rate (NR), using linear regression analysis of the log of the annual NR. We grouped countries by the year they introduced MCC vaccination into their routine immunisation programmes. ResultsThe overall NR was 0.9/100 000 population, and decreased 6.6% (95%CI: −8.0%;−5.1%) annually. Infants had the highest NR (16.0/100 000), and there were decreasing trends in all age groups <50years. Serogroup B (SgB) caused 74% of all cases, and the majority of cases in all age groups. There were decreasing trends in SgB and serogroup C (SgC) and an increasing trend in serogroup Y. Countries that introduced MCC vaccination before, and between 2004 and 2014, had decreasing trends in NR of SgC, but not countries without routine MCC vaccination. ConclusionsOur findings support evidence that routine MCC vaccination was the driving force behind the decreasing SgC trend. Vaccinating against SgB in the first year of life could help reduce the burden of IMD due to this serogroup. Changing serogroup-specific NR trends highlight the need for high-quality surveillance data to accurately assess the changing epidemiology of IMD, the effectiveness and impact of implemented vaccines, and the need for future vaccines.

Characteristics and changes in invasive meningococcal disease epidemiology in France, 2006–2015

This work aimed to describe the epidemiology of invasive meningococcal disease (IMD) in France, 2006-2015, including group- and genotype-specific disease burden, incidence trends before and after introduction of meningococcal C conjugate vaccines (MCCV) in 2010, and factors influencing the case fatality rate. Mandatory notification data on incidence and IMD case characteristics were used. Genotyping of invasive strains and whole genome sequencing were performed by the French National Reference Center. Vaccination coverage was estimated from the National Health Insurance Information System's reimbursement data. The decrease in annual IMD incidence rates (per 100,000 inhabitants) from 1.23 in 2006 to 0.78 in 2016 was mainly related to the decrease in group B IMD. Group C incidence decreased from 0.29 in 2006 to 0.13 in 2010 but increased thereafter in age groups not targeted by MCCV. From 2010 onwards, MCCV coverage gradually increased but remained below 25% in 15-19 year-olds in 2015. Age, clinical presentation and, to a lesser extent, clonal complex 11 were the most significant factors determining mortality. The limited impact of vaccination on group C IMD incidence may be explained by the emergence of a new epidemic cycle in 2011 and the low vaccination coverage rates among adolescents and young adults.

A cross-sectional vaccination coverage study in preschool children attending nurseries-kindergartens: Implications on economic crisis effect

ABSTRACTVaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs. This study assessed full and timely vaccination coverage of preschool children aged 2–3 y attending nurseries-kindergartens (N-K) nationwide at the socioeconomic crisis onset. Geographically stratified cluster sampling was implemented considering prefectures as strata and N-K as clusters. The N-K were selected by simple random sampling from the sampling frame while their number was proportional to the stratum size. In total, 185 N-K (response rate 93.9%) and 2539 children (response rate 81.5%) participated. Coverage with traditional vaccines for diphtheria-tetanus-pertussis, polio and measles-mumps-rubella was very high (>95%), followed by Haemophilus influenzae type b and varicella vaccines. Despite very high final coverage, delayed vaccination was observed for hepatitis B (48.3% completed by 12 months). Significant delay was observed for the booster dose of pneumococcal conjugate vaccines (PCV) and meningococcal C conjugate vaccines (MCC). Of the total population studied, 82.3% received 3 PCV doses by 12 months, while 62.3% received the fourth dose by 24 months and 76.2% by 30 months. However, 89.6% received at least one MCC dose over 12 months. Timely vaccinated for hepatitis A with 2 doses by 24 months were 6.1%. Coverage was significantly low for Rotavirus (<20%) and influenza (23.1% one dose). High vaccination coverage is maintained for most vaccines at the beginning of the crisis in Greece. Coverage and timeliness show an increasing trend compared to previous studies. Sustained efforts are needed to support the preventive medicine system as socioeconomic instability continues.

Reduction in Neisseria meningitidis infection in Italy after Meningococcal C conjugate vaccine introduction: A time trend analysis of 1994–2012 series

The incidence of invasive meningococcal disease (IMD) in Italy is among the lowest in Europe. Meningococcal C conjugate vaccine (MCC) was introduced in 2005 for 12 months old infants. The aim of this study was to describe the epidemiology of IMD in Italy from 1994 to 2012 and to evaluate the impact of MCC introduction. Data about Neisseria meningitidis (N. meningitidis) cases were drawn from the National Surveillance of Invasive Bacterial Diseases. The average incidence of IMD during 1994–2012 in Italy was 0.36 per 100,000 (95%CI 0.30; 0.40). N. meningitidis B was the most frequent serogroup and infants less than 12 months old were the most affected. Joinpoint analysis showed a statistically significant reduction in the incidence of N. meningitidis C related IMD after MCC introduction: the Annual Percentage Change declined from 21.8 (95%CI 15.1; 28.9) in 1994–2005 to −19.9 (95%CI −28.2; −10.7) afterwards. No changes were observed with respect to N. meningitidis B related IMD. Poisson regression showed a statistically significant reduction in the incidence of IMD both associated to N. meningitidis C (Incidence Rate Ratio 0.33; 95%CI 0.29; 0.37) and due to all serogroups (Incidence Rate Ratio 0.70; 95%CI 0.65; 0.75) in the post-vaccination period compared to the pre-vaccination one. On the other hand, the incidence of N. meningitidis B related IMD did not decrease. Our results suggest that MCC had an impact in decreasing the incidence of N. meningitidis C related IMD. However, data on typing are incomplete and efforts are needed to make them available for studying the need and the impact of other meningococcal vaccines.

Vaccine coverage estimation using a computerized vaccination registry with potential underreporting and a seroprevalence study

ObjectiveTo develop a method to estimate vaccination coverage using both a computerized vaccine registry with an unknown underreporting rate and a seroprevalence study. A real example of a meningococcal C conjugate vaccine (MCCV) coverage estimation is studied to illustrate the proposed methodology. MethodsWe reviewed the Vaccine Information System of Valencia (Sistema de Información Vacunal, SIV) for the MCCV status of 1430 subjects aged 3–29 years as part of a seroprevalence study. When MCCV was not registered in SIV, subjects were classified into three groups (MCCV non-registered, no vaccination records and missing information) depending on the registry of other vaccines. A Bayesian model was developed to ascertain the percentage of MCCV-vaccinated subjects based on the meningococcal C seroprotection levels from the seroprevalence study. ResultsThe seroprotection levels in subjects with no MCCV registered in SIV (358) were similar to those in subjects with MCCV registered (1072). This indicated a large proportion of vaccinated subjects with no MCCV registered. The estimated vaccine coverage was over 80% in all age groups, except >22 years, where it was 67.6% (95% CI: [54.0–80.4]), which corresponded to those aged over 13 years at the time of the catch-up campaign. An underreporting rate of 23.5–73.4%, depending on the age group, was estimated in those vaccinated in the 2002 catch-up campaign. ConclusionThe Bayesian model allowed for a more realistic estimation of MCCV uptake. In this example, we quantified the underreporting of a vaccine registry, especially occurring during a catch-up campaign that occurred at the establishment of the registry.

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Immunogenicity of a Single Dose of Meningococcal Group C Conjugate Vaccine Given at 3 Months of Age to Healthy Infants in the United Kingdom

From 1999, in the United Kingdom, meningococcal C conjugate (MCC) vaccines from 3 manufacturers were introduced to the infant immunization schedule at 2, 3 and 4 months of age. In 2006, the schedule was refined to a 2-dose primary schedule at 3 and 4 months of age, with a combined MCC/Haemophilus influenzae type b (MCC/Hib-TT) booster at 12 months of age. Recent data have demonstrated that 2 of the 3 MCC vaccines showed potential for use as a single priming dose in infancy. A randomized trial was undertaken with 2 MCC vaccines; one using tetanus toxoid carrier protein (MCC-TT) and one using CRM197 carrier protein (MCC-CRM197). Infants were immunized with MCC at 3 months of age followed by an MCC/Hib-TT booster at 12 months of age. The serum bactericidal antibody geometric mean titers 1 month after a single dose of MCC-TT or MCC-CRM 197 were 223.3 (95% confidence interval [CI]: 162.9-306.1) and 95.8 (95% CI: 66.4-138.2) with 100% and 95.5% of infants having serum bactericidal antibody titers ≥ 8, respectively. Before boosting, antibody titers had declined, and 1 month after the MCC/Hib-TT booster, serum bactericidal antibody geometric mean titers rose to 2251.0 (95% CI: 1535.3-3300.3) and 355.9 (95% CI: 235.4-538.1) for children primed with MCC-TT and MCC-CRM 197, respectively. In conclusion, a single priming dose of either MCC-TT or MCC-CRM197 administered at 3 months of age can be used together with the Hib/MCC-TT booster in the second year of life.

A critical appraisal of the recommendations for the use of meningococcal conjugate vaccines.

To assess the epidemiology of meningococcal disease (MD) in Brazil and the impact that recent evidence and lessons learned from the introduction of meningococcal C conjugate (MCC) vaccines into immunization programs may have on different strategies of vaccine use. Non-systematic review of the MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011. Meningococcal disease is endemic in Brazil, with periodic occurrence of outbreaks. Most cases are associated with serogroup C and the highest incidence rates are observed in infants, encouraging the introduction of MCC vaccine in the National Immunization Program in 2010 for children under 2 years old. The introduction of MCC vaccines into immunization programs in Europe, Canada and Australia proved to be effective, with dramatic reduction in the incidence of serogroup C meningococcal disease, not only in the vaccinated, but also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was dependent on a combination of antibody persistence, immunologic memory and herd protection. Recent evidence indicating that antibody persistence is not long-lasting in young immunized children, and that immunologic memory is not fast enough to protect them against the disease, emphasize the importance of herd protection to maintain the population protected. The rapid decline of antibody titers in children vaccinated in the first years of life suggests the need to incorporate booster doses before adolescence, especially in locations like Brazil, where the immunization program did not incorporate catch-up campaigns including adolescents, lacking the herd immunity effect.

No increased risk of relapse after meningococcal C conjugate vaccine in nephrotic syndrome

Objectives:To investigate whether meningococcal C conjugate vaccine (MCCV) caused relapse in children with steroid-responsive nephrotic syndrome.Design:A population-based study was conducted using an active surveillance system, developed to assess adverse events...

Immune response to conjugated meningococcal C vaccine in pediatric oncology patients

Following outbreaks of meningococcal disease in Quebec in 1991-1993 and 2000-2001, a mass vaccination campaign was performed. In 2001-2002, children aged 2 months to 20 years were immunized with the Meningococcal CRM197 vaccine (Menjugate). We examined the response of pediatric oncology patients during or following maintenance chemotherapy and post-bone-marrow transplantation to Meningococcal C vaccine. This was an open label descriptive study of a cohort of patients from the oncology clinic at the Montreal Children's Hospital. A positive vaccine response was defined as a fourfold increase in specific IgG from baseline and a bactericidal assay using human complement (hBCA) titer >1:4. Of the 25 patients with ALL, 13 had a serologic response (average 60-fold increase). The serologic responders had a higher mean B cell count (0.262) compared to non-responders 0.068 x 10.9/L [t(23) = 2.843 (P < 0.05)]. Eleven of the 12 non-responders and 4 of the responders were on maintenance chemotherapy. In addition, two of the five patients post-bone-marrow transplant, responded. Fifteen of the 34 patients (44%) had an adequate hBCA response (mean titer 61). The group included 14/18 serologic responders with hBCA response (P < 0.001) and 16/17 non-serologic responders with no hBCA response (P < 0.001). Meningococcal C-conjugate vaccine produced variable responses in children with common cancers. Proximity to chemotherapy and total B cell number may help predict likelihood of response.

Reactogenicity of Meningococcal C Conjugate Vaccines When Administered at the Same Time as, or a Month Prior to or After, Tetanus and Diphtheria Booster Vaccinations

Introduction: This single blind study was conducted to address safety concerns regarding co-administration of diphtheria/ tetanus (DT,Td) boosters and meningococcal C conjugate (MCC) vaccines containing diphtheria or tetanus conjugate proteins. Methods: 1754 subjects (835 preschoolers and 919 school leavers) were randomised to receive one of three MCC products a month before, after or at the same as routine DT or Td boosters. They (or their parents) completed a health diary for 10 days to record local reactions and systemic symptoms after each vaccination. The effect of antibody levels pre- and post-vaccination, pre-existing allergies and medication taken before and for up to ten days after vaccination on reactogenicity was assessed.Results: No relationship between pre-vaccination antibody levels and local reactions or systemic symptoms was found. Local reactions were more common after DT/Td than MCC vaccination and were related to post-vaccination diphtheria and tetanus antibody levels in younger children and to the post-vaccination tetanus only antibody levels in older children. Pre-existing allergies were not related to reactogenicity. Use of analgesics/ antipyretic medication significantly reduced the incidence of local reactions and of some systemic symptoms. In the first three days after vaccination there was an excess of some systemic symptoms including fatigue/ malaise and headache for all ages, and crying/ irritability for younger children and nausea/ vomiting and dizziness/ faintness for older subjects. Eleven serious adverse events were reported, none of which was deemed related to vaccination. Conclusion: MCC vaccines can be given under the above schedules and safely in the presence of raised diphtheria and tetanus antibody levels without materially altering reactogenicity profiles of either vaccine.