Abstract
Studies of meningococcal evolution and genetic population structure, including the long-term stability of non-random associations between variants of surface proteins, are essential for vaccine development. We analyzed the sequence variability of factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisseria adhesin A (NadA), three major antigens in the multicomponent meningococcal serogroup B vaccine 4CMenB. A panel of invasive isolates collected in the Netherlands over a period of 50 years was used. To our knowledge, this strain collection covers the longest time period of any collection available worldwide. Long-term persistence of several antigen sub/variants and of non-overlapping antigen sub/variant combinations was observed. Our data suggest that certain antigen sub/variants including those used in 4CMenB are conserved over time and promoted by selection.
Highlights
Neisseria meningitidis is a major cause of invasive bacterial meningitis and septicemia worldwide
By MultiLocus Enzyme Electrophoresis (MLEE) [3] and subsequently by MultiLocus Sequence Typing (MLST) [4], show that meningococci are structured into clonal complexes [5,6]
We investigated the prevalence and sequence variation of factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisseria adhesin A (NadA) in a panel of 165 pathogenic meningococcal isolates randomly selected from those collected in the Netherlands over a period of 50 years
Summary
Neisseria meningitidis is a major cause of invasive bacterial meningitis and septicemia worldwide. Meningococcal populations are highly diverse, and engage in extensive genetic exchange [1,2]. Isolates belonging to the different clonal complexes exhibit different phenotypes and vary in their propensity to cause disease [7,8,9]. Meningococcal isolates belonging to the hypervirulent clonal complexes (cc), cc11, cc, cc41/44, cc, cc4 and cc, have a high capacity to cause invasive disease. Cc269 could be considered hypervirulent [10]. Strains belonging to the hypervirulent clonal complexes are over-represented in collections of pathogenic isolates. Clonal complexes are relatively genetically stable over time, despite high rates of recombination [4]. Strains associated with asymptomatic carriage exhibit more extensive genetic diversity [12]
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