Antibody persistence after serogroup C meningococcal conjugate vaccine in children with sickle cell disease

BackgroundA decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed.MethodsSCD patients (n = 141) previously immunized with MCC vaccines had blood drawn 2–8 years after the last priming dose. They were distributed according to age at primary immunization into groups: <2 years and 2–13 years and evaluated by years since vaccination (2–3, 4–5 and 6–8). Serum bactericidal antibodies with baby rabbit complement (rSBA) and serogroup C-specific IgG concentrations were measured. The correlate of protection was rSBA titer ⩾8. Subjects with rSBA <8 received a booster dose and antibody levels re-evaluated after 4–6 weeks.ResultsFor children primed under 2 years of age rSBA titer ⩾8 was demonstrated in 53.3%, 21.7% and 35.0%, 2–3, 4–5, 6–8 years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2–13 years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers ⩾8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM₁₉₇ [Menjugate® (33.3%) or Meningitec® (35.7%)] (p = 0.033). After a booster, 98% achieved rSBA titer ⩾8.ConclusionImmunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC-CRM₁₉₇.     

The bivalent factor H binding protein meningococcal serogroup B vaccine elicits bactericidal antibodies against representative non-serogroup B meningococci

MenB-FHbp (Trumenba®; bivalent rLP2086) is a meningococcal serogroup B vaccine containing 2 variants of the recombinant lipidated factor H binding protein (FHbp) antigen. The expression of FHbp, an outer membrane protein, is not restricted to serogroup B strains of Neisseria meningitidis (MenB). This study investigated whether antibodies elicited by MenB-FHbp vaccination also protect against non-MenB strains. Immunological responses were assessed in serum bactericidal assays using human complement (hSBAs) with non-MenB disease-causing test strains from Europe, Africa, and the United States. Importantly, FHbp variant distribution varies among meningococcal serogroups; therefore, strains that code for serogroup-specific prevalent variants (ie, representative of the 2 antigenically distinct FHbp subfamilies, designated subfamily A and subfamily B) and with moderate levels of FHbp surface expression were selected for testing by hSBA. After 2 or 3 doses of MenB-FHbp, 53% to 100% of individuals had bactericidal responses (hSBA titers ≥ 1:8) against meningococcal serogroup C, W, Y, and X strains, and 20% to 28% had bactericidal responses against serogroup A strains; in fact, these bactericidal responses elicited by MenB-FHbp antibodies against non-MenB strains, including strains associated with emerging disease, were greater than the serological correlate of protection for meningococcal disease (ie, hSBA titers ≥ 1:4). This is in comparison to a quadrivalent polysaccharide conjugate vaccine, MCV4 (Menactra®, targeting meningococcal serogroups A, C, W, and Y), which elicited bactericidal responses of 90% to 97% against the serogroup A, C, W, and Y strains and had no activity against serogroup X. Together, these results provide clinical evidence that MenB-FHbp may protect against meningococcal disease regardless of serogroup.     

Evaluation of meningococcal serogroup C conjugate vaccine programs in Canadian children: interim analysis

Background

To assess antibody titers afforded by meningococcal C- (MenC) tetanus toxoid conjugate vaccine at 12 months of age in three different immunization schedules.

Methods

This prospective study included three similar cohorts of healthy infants from 1-dose, 2-dose and 3-dose MenC infant immunization programs. Infants were enrolled at 12 months of age and given the final scheduled dose of MenC-tetanus toxoid conjugate vaccine with sera collected prior to and 1 month after the vaccination. Serum bactericidal activity (SBA) titers ≥ 1:8 were considered protective.

Results

Before the 12 month dose, participants had significantly different protective titers according to the number of prior doses received: 100% (95% CI 97.6–100%) of infants who had 2 prior doses (at 2 and 4 months) were protected compared to 84.0% (76.7–89.3%) of participants with one dose (at 2 months) and 27.6% (21.0–35.4%) of unvaccinated infants. All subjects were protected after the 12 month MenC dose, but titers were higher with prior priming.

Conclusions

Two MenC doses given in infancy afford optimal protection during the first year of life; however, substantial protection was seen after one dose at 2 months.     

Multicomponent meningococcal serogroup B vaccination elicits cross-reactive immunity in infants against genetically diverse serogroup C,W and Y invasive disease isolates

BackgroundThe multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains.MethodsA total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB.ResultsSerogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%.ConclusionThis is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination.     

Impact of mass vaccination with polysaccharide conjugate vaccine against serogroup C meningococcal disease in Spain

During the fourth quarter of 1997, a vaccination campaign using the meningococcal C polysaccharide vaccine was carried out in 14 autonomous regions of Spain. The remaining three regions did not participate. In the last quarter of the year 2000, a mass vaccination campaign using the meningococcal C conjugated vaccine was carried out in all regions. In the year 2001 the incidence decreased in all regions, although the decrease was greater in regions that did not vaccinate in 1997. In contrast, case fatality rates did not decrease. During 2001, the incidence rate of meningococcal C disease was still lower (0.32 per 100000 persons-year) in the regions that vaccinated in 1997 with the polysaccharide vaccine than in those that did not (0.64 per 100000 persons-year).     

Long-term persistence of protective antibodies in Dutch adolescents following a meningococcal serogroup C tetanus booster vaccination

IntroductionDue to waning immunity, infant vaccination with meningococcal serogroup C conjugated (MenCC) vaccines is insufficient to maintain long-term individual protection. Adolescent booster vaccination is thought to offer direct protection against invasive meningococcal disease (IMD) but also to reduce meningococcal carriage and transmission and in this way establish herd protection in the population. Previously, we studied antibody levels after adolescent MenCC booster vaccination. In the present study, the adolescent vaccinees were revisited after three years to determine antibody persistence and to predict long-term protection.MethodsMeningococcal serogroup C tetanus toxoid conjugated (MenC-TT) vaccine was administered to 10-, 12- and 15-year old participants who had been primed nine years earlier with a single dose of MenC-TT vaccine. Blood samples were collected before, 1 month, 1 year and 3 years after the adolescent booster vaccination. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (rSBA). Meningococcal serogroup C polysaccharide and tetanus toxoid specific antibody levels were measured using fluorescent-bead-based multiplex immunoassay. Long-term protection was estimated using longitudinal multilevel antibody decay modeling.ResultsOf the original 268 participants, 201 (75%) were revisited after 3 years. All participants still had an rSBA titer above the protective threshold of ⩾8 and 98% ⩾128. The 15-year-olds showed the highest antibody titers. Using a bi-exponential decay model, the median time to fall below the protection threshold (rSBA titer <8) was 16.3 years, 45.9 years and around 270 years following the booster for the 10-, 12- and 15-year-olds, respectively.ConclusionsAfter a first steep decline in antibody levels in the first year after the booster, antibody levels slowly declined between one and three years post-booster. A routine MenC-TT booster vaccination for adolescents in the Netherlands will likely provide long-term individual protection and potentially reduce the risk of resurgence of MenC disease in the general population.     

血清杀菌试验和酶联免疫吸附试验测定C群脑膜炎奈瑟菌血清抗体滴度比较

目的 比较血清杀菌试验(SBA)和酶联免疫吸附试验(ELISA)测定两种C群脑膜炎奈瑟菌(Nm)疫苗免疫后血清抗体滴度的差异.方法 采用SBA测定75名未免疫健康成年人(40～70岁)血清、143名3～8月龄婴儿及194名3～5岁儿童NmA和C群结合疫苗或A+C群多糖疫苗免疫前后血清中Nm杀菌抗体水平,然后用ELISA测定相应血清的Nm特异性IgG含量,并利用线性相关与回归分析两种测定结果的相关性.结果 未免疫健康成年人血清中Nm杀菌抗体水平和特异性IgG含量之间的相关性较高(r=0.814 33,P＜0.001);3～8月龄婴儿和3～5岁儿童接种结合/多糖疫苗前,Nm杀菌抗体水平和特异性IgG含量之间相关性较差(3～8月龄:r=0.140 64,P＞0.l00/r=0.2899,P＜0.05;3 ～5岁:r=0.540 40,P＜0.05/r=0194 36,P＜0.05),接种1剂结合疫苗后,杀菌抗体水平和特异性IgG含量之间的相关性较好(r=0.809 38,P＜0.001和r=0.837 23,P＜0.001);接种多糖疫苗后,杀菌抗体水平和特异性IgG含量之间的相关性较差(r＜0.500 00).结论 健康成年人血清和结合疫苗免疫后的婴幼儿血清中特异性C群Nm IgG含量可以间接反映血清杀菌抗体水平,ELISA方法可以替代SBA.但ELISA检测方法不适用于3～8月龄婴儿多糖疫苗免疫后的效果评价.     

Impact of vaccination during an epidemic of serogroup C meningococcal disease in Salvador, Brazil

To combat rising incidence of serogroup C meningococcal disease in the city of Salvador, Brazil, the Bahia state immunization program initiated routine childhood immunization with meningococcal C conjugate vaccine (MenC) in February 2010, followed by mass MenC vaccination of city residents 10-24 years of age from May through August 2010. We analyzed trends in incidence of reported cases of meningococcal disease and serogroup distribution among meningococcal isolates identified in hospital-based surveillance in Salvador from January 2000 to December 2011 and estimated vaccine effectiveness using the screening method. Annual incidence of serogroup C meningococcal disease increased from 0.1 cases per 100,000 population during 2000-2006 to 2.3 in 2009 and 4.1 in 2010, before falling to 2.0 per 100,000 in 2011. Estimated coverage of mass vaccination reached 80%, 67% and 41% among 10-14, 15-19 and 20-24 year olds, respectively. Incidence in 2011 was significantly lower than average rates in 2008-2009 among children <5 years, but reductions among 10-24 year olds were not significant. Among 10-24 year olds, a single dose of MenC vaccine was 100% effective (95% confidence interval, 79-100%) against serogroup C meningococcal disease. Low coverage in the population targeted for mass vaccination may have limited impact on ongoing transmission of serogroup C meningococcal disease despite high vaccine effectiveness.     

Impact of a mass vaccination campaign against Serogroup B meningococcal disease in the Saguenay-Lac-Saint-Jean region of Quebec four years after its launch

In the Saguenay-Lac-Saint-Jean region of Quebec, 83% of the population ≤20 years (n ≅ 59,500) was immunized in 2014 with the four-component Serogroup B meningococcal vaccine to control a long-lasting outbreak caused by a virulent ST-269 Serogroup B Neisseria meningitidis clone. Following the campaign, invasive meningococcal B disease (B-IMD) incidence fell sharply in the target population from 11.4/100,000 in 2006–2014 to 0.4/100,000 in 2014–2018 (p < 0.0001). Five B-IMD cases occurred in the region from July 2014 to June 2018, including one vaccinated child, one unvaccinated young adult and 3 unvaccinated elderly adults. Estimate of direct vaccine protection was 79% [95%CI:−231%;99%]. The overall campaign impact in the region taking into account the decrease in B-IMD incidence at provincial level was a 86% [95%CI:−2%;98%] decrease in B-IMD risk. The campaign impact was mostly seen in the target age-group suggesting no herd effect among unvaccinated older adults.     

Meningococcal C conjugate vaccine effectiveness before and during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C/cc11, Tuscany,Italy

IntroductionIn Tuscany, Italy, where a universal immunization program with monovalent meningococcal C conjugate vaccine (MCC) was introduced in 2005, an outbreak of invasive meningococcal disease (IMD) due to the hypervirulent strain of Neisseria meningitidis C/cc11 occurred in 2015–2016, leading to an immunization reactive campaign using either the tetravalent (ACWY) meningococcal conjugate or the MCC vaccine. During the outbreak, IMD serogroup C (MenC) cases were also reported among vaccinated individuals. This study aimed to characterize meningococcal C conjugate vaccines (MenC-vaccines) failures and to estimate their effectiveness since the introduction (2005–2016) and during the outbreak (2015–2016).MethodsMenC cases and related vaccine-failures were drawn from the National Surveillance System of Invasive Bacterial Disease (IBD) for the period 2006–2016. A retrospective cohort-study, including the Tuscany' population of the birth-cohorts 1994–2014, was carried out. Based on annual reports of vaccination, person-years of MenC-vaccines exposed and unexposed individuals were calculated by calendar-year, birth-cohort, and local health unit. Adjusted (by birth-cohort, local health unit, and calendar-year) risk-ratios (ARR) of MenC invasive disease for vaccinated vs unvaccinated were estimated by the Poisson model. Vaccine-effectiveness (VE) was estimated as: VE = 1-ARR.ResultsIn the period 2006–2016, 85 MenC-invasive disease cases were reported; 61 (71.8%) from 2015 to 2016. Twelve vaccine failures occurred, all of them during the outbreak. The time-interval from immunization to IMD onset was 20 days in one case, from 9 months to 3 years in six cases, and ≥7 years in five cases. VE was, 100% (95%CI not estimable, p = 0.03) before the outbreak (2006–2014) and 77% (95%CI 36–92, p < 0.01) during the outbreak; VE was 80% (95%CI 54–92, p < 0.01) during the overall period.ConclusionsIn Tuscany, MenC-vaccine failures occurred exclusively during the 2015–2016 outbreak. Most of them occurred several years after vaccination. VE during the outbreak-period was rather high supporting an effective protection induced by MenC-vaccines.     

Carrier priming effect of CRM197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM197 and diphtheria toxoid

Glycoconjugate vaccines are composed of capsular polysaccharides (CPSs) of a pathogenic bacteria covalently linked to carrier proteins. Pre-exposure to the carrier is known to influence the efficacy of the glycoconjugate, by inducing enhanced or suppressed anti-CPS response. Following our previous work on the immunogenicity of diphtheria toxin mutant CRM₁₉₇ and formaldehyde-treated diphtheria toxoid (DT) as carriers for meningococcal A (MenA) conjugates in mouse model, we further investigated the role of the carrier on the immunological response to glycoconjugate vaccines. We previously showed that high dosage DT priming could result in carrier-induced epitopic suppression (CIES), an event that did not occur for CRM₁₉₇ priming, and we observed that anti-DT IgGs could cross-react with DT based conjugates in vitro. Here, we confirmed the cross-reactivity of anti-carrier IgGs with DT conjugates in vivo. Furthermore, we analyzed the splenocytes of animals primed with the carrier and subsequently immunized with the MenA conjugate. Pre-exposure to the carrier protein, both CRM₁₉₇ and DT, resulted in increased carrier-specific plasma and memory B cell response. However, only for CRM₁₉₇ priming an enhanced carbohydrate-specific plasma cell response was observed. Analysis of circulating IgGs confirmed these observations. Memory to the CPS resulted to be non-influenced by carrier priming. Analysis of T helper response showed an enhancement effect for CRM₁₉₇ priming, while DT priming resulted in constrained T cell activation. Stimulation with CRM₁₉₇, which does not require formaldehyde detoxification, of splenocytes from animal immunized with DT suggested that the formaldehyde treatment used to produce DT might be the cause of limited presentation of the antigen to the T cells. We concluded that the dominant carrier-specific B cell response in case of limited T cell recruitment might explain the previously observed CIES phenomenon in case of DT priming.     

Immune responses following meningococcal serogroups A,C, Y and W polysaccharide vaccination in C2-deficient persons: Evidence for increased levels of serum bactericidal antibodies

Complement C2 deficiency (C2D) is associated with immunological diseases and increased susceptibility to invasive infections caused by encapsulated bacteria such as Neisseria menigitidis. In this study we evaluate the immunogenicity of vaccination against N. menigitidis in C2D.C2D patients (n = 22) and controls (n = 52) were given a tetravalent meningococcal polysaccharide vaccine. Serum bactericidal antibody (SBA) titres (serogroups A, C, Y and W) were analysed using a rabbit complement source. Levels of IgG, IgM, and IgA, factor B, and factor H, polymorphisms of MBL and Fc-gamma receptors were determined.The C2D patients responded with an increased SBA titre to all four serogroups (p < 0.001). The response rates define as SBA titres ≥8 were found to be between 85.7% and 92.5%. The post-vaccination titres for serogroups C, Y and W were equal to healthy controls. C2D patients with a history of invasive infection had a lower post-vaccination SBA titres both compared to healthy C2D persons (p = 0.03) and compared to controls (p < 0.0001). We found that the G2M*n/G2M*n genotype were associated with a higher SBA titres after immunization (p = 0.03). None of the other investigated immunological factors appear to be important in influencing the vaccine responses. Autoimmune diseases in C2D did not affect the vaccine response.In general, vaccination against meningococci gave rise to antibody responses in the C2D patients that equal healthy controls. The response rate was lower to serogroup A and among C2D patients with history of invasive infections. The presence of G2M*n/G2M*n genotype was associated with higher SBA titres after immunization.     

Concomitant administration of a fully liquid,ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants.This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46–74 days (n = 350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n = 175) or without MenC vaccine (Group 2; n = 175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines.The proportion of participants with an anti-HBs concentration ⩾10 mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1–99.3] in the coadministration group and 96.1% [95%CI: 91.8–98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved.Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups.ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.     

Effectiveness of a single dose of the quadrivalent meningococcal conjugate vaccine,MenACWY-CRM,in the Korean Armed Forces

Conjugate vaccines are widely used to overcome the disadvantages of polysaccharide vaccines in the prevention of meningococcal disease. However, limited studies have examined the clinical effectiveness of single-dose meningococcal quadrivalent conjugate vaccines in adults. We assessed the effectiveness of the meningococcal vaccination program in the Republic of Korea Armed Forces, since 2013. Following vaccination program implementation, meningococcal disease cases decreased from 0.52/100,000 to 0.06/100,000 and the number of deaths declined from four to zero. Two meningococcal cases that developed post-implementation were identified as serotype B and X. The effectiveness of single-dose conjugate vaccination in recruits, expressed as the incidence rate ratio, was 0.88 during a 19–23-month observation period. These results indicate that meningococcal infections can be prevented by single-dose administration of the quadrivalent conjugate vaccine in at-risk groups, such as soldiers, travelers, and students in dormitories. Continuous investigation is needed to determine serogroup change, including B serogroups.     

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.     

Interchangeability of meningococcal group C conjugate vaccines with different carrier proteins in the United Kingdom infant immunisation schedule

An open, non-randomised study was undertaken in England during 2011–12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (P < 0.001) according to MCC vaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39–173; n = 14) compared to those receiving two MCC-CRM (418; 95% CI, 325–537; n = 82), two MCC-TT (277; 95% CI, 223–344; n = 79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322–949; n = 18). The same group also had the lowest Hib geometric mean concentrations (0.60 μg/mL, 0.27–1.34) compared to 1.85 μg/mL (1.23–2.78), 2.86 μg/mL (2.02–4.05) and 4.26 μg/mL (1.94–9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible.     

Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel

Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYW_D) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYW_D or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYW_D from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5–7, 11–13, 17–19, 23–25, 29–31, or 35–37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWY_D group. rSBA GMT increased to 703 at 5–7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWY_D group at 5–7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWY_D recipients achieving an rSBA titer of ≥8 decreased from 87% at 5–7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ≥8 at any time-point. GMC for the MenACWY_D group was 0.14 μg/mL at baseline, 1.07 μg/mL at 5–7 months, and 0.66 μg/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYW_D; a booster dose is needed to maintain protective levels of circulating antibody.     

Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease.     

Seroprevalence of IgG antibodies against 13 vaccine Streptococcus pneumoniae serotypes in the Netherlands

In this study the seroprevalence of IgG antibodies against 13 vaccine serotypes of the pneumococcus was assessed in the Netherlands. Sera from 7904 persons obtained in a cross-sectional population-based study were analysed. The 13 serotype specific IgG concentrations were assessed simultaneously using a fluorescent bead-based multiplex immuno assay (MIA).Overall, the geometric mean IgG concentrations (GMCs) against the 13 serotypes in unvaccinated individuals increased with age up to 5 years and remained at a plateau thereafter. The data also show that individuals develop antibodies against an increasing number of different serotypes with increasing age. The highest GMCs were found for antibodies directed against serotype 14 and 19F, whereas antibodies against serotypes 4 and 5 had the lowest GMCs. There was no uniform relationship between the occurrence of serotypes causing invasive pneumococcal disease (IPD) and the GMCs against these serotypes. Increased IPD incidence in the elderly did not seem to be the result of a decline in the concentration of IgG antibodies.