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Variation of the factor H-binding protein in Neisseria meningitidis, Carina Brehony in Martin Maiden's lab at Oxford investigated a group of outer membrane proteins in the bacterium responsible for meningococcal meningitis. To date, attempts to raise a vaccine against the common serogroup B meningococci have been frustrated by the low immunogenicity of the serogroup B capsular polysaccharide, despite success with serogroups A and C. Outer membrane proteins, such as factor H-binding protein (fHbp) may provide alternative targets for vaccine development.
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However, fHbp is genetically diverse, and our investigation showed evidence of structuring into three groups. OmegaMap analyses of the three groups revealed a signature consistent with strong selection pressure for antigenic variability at the gene. Notably, there was clear evidence of diversifying selection at several previously discovered epitopes - positions in the protein targeted by antibodies during bacteria-killing immune response. (Analysis of one group is shown in the figure, with known epitopes marked).
While these observations are encouraging in terms of understanding the biology of pathogen antigens, a pressing question is how do we translate that understanding into practical vaccine design? Studies such as ours suggest a multi-component vaccine may be necessary to achieve broad coverage against serogroup B meningococci.
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