Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation

AbstractSerogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8–30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates

Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W Meningococcal Disease, England, 2015–2016

During the first 12 months of an emergency meningococcal ACWY vaccination program for teenagers in England, coverage among persons who left school in 2015, the first cohort to be vaccinated, was 36.6%. There were 69% fewer group W meningococcal cases than predicted by trend analysis and no cases in vaccinated teenagers

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage

AbstractBackground4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology.ObjectiveTo experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting.Methods and resultsWe used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007–2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P=0.022). MATS predicted coverage of 70% (95% CI, 55–85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72–95%). MATS had 78% accuracy and 96% positive predictive value against hSBA.ConclusionMATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents

Knowledge, beliefs and practices regarding prevention of bacterial meningitis in Burkina Faso, 5 years after MenAfriVac mass campaigns.

BACKGROUND: To adapt communications concerning vaccine prevention, we studied knowledge, beliefs and practices around meningitis risk and prevention in a young adult population in Burkina Faso in 2016, 5 years after the MenAfriVac® mass campaign and one year before the vaccine's inclusion in the infant immunization schedule. METHODS: In a representative sample of the population aged 15 to 33 years (N = 220) in Bobo-Dioulasso, Burkina Faso, study nurses administered a standardized paper questionnaire consisting of predominantly open questions, collecting information on meningitis risk factors and prevention, and on exposure to dry air and kitchen fire smoke. We identified themes and analyzed their frequency. We created a meningitis knowledge score (range 0 to 4) based on pre-defined best responses and analyzed the determinants of knowledge score levels ≥2 (basic score) and ≥3 (high score) using multivariate logistic regression. RESULTS: Biomedically supported facts and good practices were known by the majority of participants (eg vaccine prevention, 84.5%). Younger women aged 15-20 years had a higher frequency of low scores <2 (17.0%) compared to older women aged 21-33 years (6.3%) and men of both age groups (3.8%). Junior secondary School attendance explained the differences between the two groups of women, the gender gap for the older, but not the young women, and explained score differences among young women. Local understandings and practices for risk and prevention were commonly reported and used (risk from unripe mango consumption and prevention through nasal application of shea nut butter). DISCUSSION: This study shows a gender gap in knowledge of meningitis risk and prevention, largely due to education-level inequalities. Women below 21 years had particularly low levels of knowledge and may need interventions outside schools and perinatal care. Our study suggests a strong adherence to local understandings of and practices around meningitis risk and prevention, which should be taken into account by vaccination promotion

Neisseria meningitidis nasopharyngeal carriage during the Hajj: A cohort study evaluating the need for ciprofloxacin prophylaxis

Background The annual Muslim pilgrimage has the potential of increase risk for acquisition of Neisseria meningitidis. Here, we evaluate the Hajj impact on the prevalence of N. meningitidis carriage in a paired and non-paired cohort of pilgrims. Secondary objectives were to calculate the compliance with recommended vaccination. Methods This is a prospective paired (arriving and departing), non-paired arriving and non-paired departing cohort study with the collection of nasopharyngeal samples at the start and the end of the Hajj. Results The study included unpaired arriving pilgrims at King Abdul Aziz International Airport (N = 1055), unpaired departing cohort (N = 373), and a paired cohort (N = 628) who were tested on arrival and departure. Meningococcal vaccination was received by all pilgrims, 98.2% received quadrivalent polysaccharide vaccine (ACWY), and 1.8% received meningococcal quadrivalent conjugate vaccine (MCV4). Only 1.61% and 23.03% received pneumococcal and influenza vaccines, respectively. Of the 1055 arriving unpaired pilgrim, 36 (3.4%) tested positive for nasopharyngeal carriage of N. meningitidis, and 24 (66.7%) of these were serogroup B, the remainder were non-groupable. Haemophilus influenza was detected among 45 (4.3%), and 11 (1%) carriers were positive for both N. meningitidis and H. influenzae. Out of 373 in the unpaired departing cohort, 6 (1.61%) tested positive for N. meningitidis, and 34 (9.1%) were positive for H. influenzae. Of the 628 paired cohort pilgrims, 36 (5.7%) pilgrims were positive for N. meningitidis at arrival and 16 (2.5%) pilgrims were positive after the hajj. Conclusion This the largest study of the epidemiology of N. meningitidis among pilgrims. The study showed a significant difference in the carriage between pilgrims from high endemicity and other pilgrims with a predominance of serogroup B. The continued use of ciprofloxacin as prophylactic antibiotics should be reconsidered as well as the consideration to add serogroup B as a required vaccination

Temporal associations between national outbreaks of meningococcal serogroup W and C disease in the Netherlands and England: an observational cohort study.

Since 2009, the incidence of meningococcal serogroup W disease has increased rapidly in the UK because of a single strain (the so-called original UK strain) belonging to the hypervirulent sequence type-11 clonal complex (cc11), with a variant outbreak strain (the so-called 2013 strain) emerging in 2013. Subsequently, the Netherlands has had an increase in the incidence of meningococcal serogroup W disease. We assessed the temporal and phylogenetic associations between the serogroup W outbreaks in the Netherlands and England, and the historical serogroup C outbreaks in both countries

Using the Indirect Cohort Design to Estimate the Effectiveness of the Seven Valent Pneumococcal Conjugate Vaccine in England and Wales

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2, 3 and 13 month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD. METHODS AND FINDINGS: We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%. CONCLUSIONS: This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine

Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali.

BACKGROUND: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. METHODS: Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. RESULTS: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination. CONCLUSIONS: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity

Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England

Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain