Antigenic Diversity of Meningococcal Enterobactin Receptor FetA, a Vaccine Component

Microbiology. 2003 Jul;149(Pt 7):1849-1858. doi: 10.1099/mic.0.26131-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antigenic Variation
  • Antigens, Bacterial / genetics
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Base Sequence
  • DNA, Bacterial / genetics
  • Genes, Bacterial
  • Immunochemistry
  • Immunodominant Epitopes / genetics
  • Meningococcal Vaccines / genetics*
  • Meningococcal Vaccines / immunology*
  • Mice
  • Molecular Sequence Data
  • Neisseria meningitidis / genetics
  • Neisseria meningitidis / immunology*
  • Phylogeny
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • DNA, Bacterial
  • FrpB protein, bacteria
  • Immunodominant Epitopes
  • Meningococcal Vaccines
  • Receptors, Cell Surface

Associated data

  • GENBANK/AF439155
  • GENBANK/AF439156
  • GENBANK/AF439157
  • GENBANK/AF439158
  • GENBANK/AF439159
  • GENBANK/AF439160