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Variation of the factor H-binding protein of Neisseria meningitidis

¹ Department of Zoology, University of Oxford, OX1 3PS, UK
² Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC #410, Chicago, IL 60637, USA

There is currently no comprehensive meningococcal vaccine, due to difficulties in immunizing against organisms expressing serogroup B capsules. To address this problem, subcapsular 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 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 recognized by previously described bactericidal monoclonal antibodies.

Correspondence
Carina Brehony
carina.brehony{at}zoo.ox.ac.uk

Two supplementary figures, showing distribution of clonal complexes within fHbp peptide alleles and a neighbour-joining tree constructed from aligned peptide sequences indicating association with clonal complex, are available with the online version of this paper.