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Variation of the factor H-binding protein of Neisseria meningitidis

¹ University of Oxford;
² University of Chicago;
³ Univeristy of Oxford

There is currently no comprehensive meningococcal vaccine, due to difficulties in immunising against organisms expressing serogroup B capsules. To address this problem, sub-capsular antigens, particularly the outer membrane proteins (OMPs), are being investigated as candidate vaccine components. If immunogenic, however, such antigens are often antigenically variable and knowledge of the extent and structuring of this diversity is an essential part of vaccine formulation. Factor H-binding protein (fHbp) is one such protein and is included in two vaccines under development. A survey of the diversity of the fHbp gene and the encoded protein in a representative sample of meningococcal isolates confirmed that variability in this protein is structured into two or three major groups, each with a substantial number of alleles that have some association with meningococcal clonal complexes and serogroups. A unified nomenclature scheme was devised to catalogue this diversity. Analysis of recombination and selection on the allele sequences demonstrated that the parts of the gene are subject to positive selection, consistent with immune selection on the protein generating antigenic variation, particularly in the C-terminal region of the peptide sequence. The highest levels of selection were observed in regions corresponding to epitopes recognised by previously described bactericidal monoclonal antibodies.

⁴ E-mail: carina.brehony{at}zoo.ox.ac.uk