A Multi-country Evaluation of Neisseria meningitidis Serogroup B Factor H–Binding Proteins and Implications for Vaccine Coverage in Different Age Groups

Abstract

Recombinant vaccines containing factor H-binding protein (fHBP) have been developed for the purpose of protection from invasive meningococcal serogroup B disease. Neisseria meningitidis fHBP sequences can be divided into 2 genetically and immunologically distinct subfamilies (A and B); thus, cross protection is conferred within but not between subfamilies. A comprehensive understanding of fHBP epidemiology is required to accurately assess the potential vaccine impact when considering different vaccination implementation strategies. Systematically collected invasive meningococcal serogroup B isolates from England, Wales, Northern Ireland, the United States, Norway, France and the Czech Republic were previously characterized for fHBP sequence. This study expanded the evaluation with additional meningococcal serogroup B disease isolates from Spain (n = 346) and Germany (n = 205). This expanded set (n = 1841), collected over a 6-year period (2001 to 2006), was evaluated for fHBP sequence and fHBP subfamily relative to patient age. All 1841 isolates contained fhbp. fHBP sequences from Spain and Germany fell within the previously described subfamilies, with 69% of isolates belonging to subfamily B and 31% to subfamily A; prevalent sequence variants were also similar. Stratification of data by age indicated that disease in infants <1 year of age was caused by a significantly higher proportion of isolates with fHBP subfamily A variants than that seen in adolescents and young adults 11-25 years (47.7% versus 19.5%, P < 0.0001, respectively). These observations highlight a difference in epidemiology of fHBP subfamilies in different age groups, with fHBP subfamily A strains causing more disease in vulnerable populations, such as infants, than in adolescents.