Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complement-mediated killing of invasive NmB isolates in a serum bactericidal assay with human complement (hSBA). The vaccine consists of two factor H binding proteins (fHBPs) representing divergent subfamilies to ensure broad coverage. Although it is the surrogate of efficacy, an hSBA is not suitable for testing large numbers of strains in local laboratories. Previously, an association between the in vitro fHBP surface expression level and the susceptibility of NmB isolates to killing was observed. Therefore, a flow cytometric meningococcal antigen surface expression (MEASURE) assay was developed and validated by using an antibody that binds to all fHBP variants from both fHBP subfamilies and accurately quantitates the level of fHBP expressed on the cell surface of NmB isolates with mean fluorescence intensity as the readout. Two collections of invasive NmB isolates (n = 1,814, n = 109) were evaluated in the assay, with the smaller set also tested in hSBAs using individual and pooled human serum samples from young adults vaccinated with bivalent rLP2086. From these data, an analysis based on fHBP variant prevalence in the larger 1,814-isolate set showed that >91% of all meningococcal serogroup B isolates expressed sufficient levels of fHBP to be susceptible to bactericidal killing by vaccine-induced antibodies.IMPORTANCE Bivalent rLP2086 (Trumenba) vaccine, composed of two factor H binding proteins (fHBPs), was recently licensed for the prevention of N. meningitidis serogroup B (NmB) disease in individuals 10 to 25 years old in the United States. This study evaluated a large collection of NmB isolates from the United States and Europe by using a flow cytometric MEASURE assay to quantitate the surface expression of the vaccine antigen fHBP. We find that expression levels and the proportion of strains above the level associated with susceptibility in an hSBA are generally consistent across these geographic regions. Thus, the assay can be used to predict which NmB isolates are susceptible to killing in the hSBA and therefore is able to demonstrate an fHBP vaccine-induced bactericidal response. This work significantly advances our understanding of the potential for bivalent rLP2086 to provide broad coverage against diverse invasive-disease-causing NmB isolates.
- MeSH
- antibakteriální látky farmakologie MeSH
- antigeny bakteriální analýza MeSH
- bakteriální proteiny analýza MeSH
- baktericidní aktivita krve MeSH
- lidé MeSH
- meningokokové vakcíny imunologie MeSH
- mikrobiální viabilita účinky léků MeSH
- Neisseria meningitidis séroskupiny B chemie účinky léků izolace a purifikace fyziologie MeSH
- protilátky bakteriální farmakologie MeSH
- průtoková cytometrie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
- MeSH
- antigeny bakteriální analýza genetika imunologie MeSH
- bakteriální proteiny analýza genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- meningokokové infekce epidemiologie imunologie mikrobiologie prevence a kontrola MeSH
- meningokokové vakcíny aplikace a dávkování imunologie MeSH
- mladiství MeSH
- Neisseria meningitidis chemie imunologie izolace a purifikace MeSH
- předškolní dítě MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
