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

Abstract

Background: 4CMenB (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.

Objective: To experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting.

Methods and results: We 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.

Conclusion: MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents.

Keywords: 4CMenB vaccine strain coverage; CC; ELISA; FN; FP; HPA; Health Protection Agency; IMD; MATS; MLST; MenB; Meningococcal Antigen Typing System; NHBA; NadA; Neisseria meningitidis serogroup B; Neisserial adhesin A; Neisserial heparin binding antigen; OMV; PBT; PorA; RP; SBA; ST; Serum bactericidal antibody assay; Stratified proportional sampling; TN; TP; capsular group B meningococcus; clonal complex; enzyme-linked immunosorbent assay; fHBP; factor H binding protein; false negatives; false positives; hSBA; invasive meningococcal disease; multilocus sequence typing; outer membrane vesicle; porin A; positive bactericidal threshold; relative potency; sequence type; serum bactericidal antibody; serum bactericidal antibody assay with human complement; true negatives; true positives.