Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

1 The Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3SY, UK 2 National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK Correspondence Martin C. J. Maiden maiden{at}zoo.ox.ac.uk Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component. Abbreviations: OMP, outer-membrane protein; OMV, outer-membrane vesicle; VR, variable region The GenBank accession numbers for the sequences reported in this paper are AF439155 – AF439260 .