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Volume 149, Issue 7

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component Free

Abstract

Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 alleles, encoding 56 protein sequences, were identified from 107 representative 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.

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Keyword(s): OMP, outer-membrane protein , OMV, outer-membrane vesicle and VR, variable region
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2003-07-01
2024-04-23
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References

  1. Ala'Aldeen D. A., Davies H. A., Borriello S. P. 1994; Vaccine potential of meningococcal FrpB: studies on surface exposure and functional attributes of common epitopes. Vaccine 12:535–541
     [Google Scholar]
  2. Bandelt H. J., Dress A. W. 1992; Split decomposition: a new and useful approach to phylogenetic analysis of distance data. Mol Phylogenet Evol 1:242–252
     [Google Scholar]
  3. Beucher M., Sparling P. F. 1995; Cloning, sequencing, and characterization of the gene encoding FrpB, a major iron-regulated, outer membrane protein of Neisseria gonorrhoeae . J Bacteriol 177:2041–2049
     [Google Scholar]
  4. Bjune G., Høiby E. A., Grønnesby J. K. 14 other authors 1991; Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338:1093–1096
     [Google Scholar]
  5. Black J. R., Dyer D. W., Thompson M. K., Sparling P. F. 1986; Human immune response to iron-repressible outer membrane proteins of Neisseria meningitidis . Infect Immun 54:710–713
     [Google Scholar]
  6. Boslego J., Garcia J., Cruz C. 11 other authors 1995; Efficacy, safety, and immunogenicity of a meningococcal group B (15 : P1.3) outer membrane protein vaccine in Iquique, Chile. Vaccine 13:821–829
     [Google Scholar]
  7. Bremner C., Lennon D., Martin D., Baker M., Rumke H. 1999; Epidemic meningococcal disease in New Zealand: epidemiology and potential for prevention by vaccine. N Z Med J 112:257–259
     [Google Scholar]
  8. Brunham R. C., Plummer F. A., Stephens R. S. 1993; Bacterial antigenic variation, host immune response, and pathogen–host coevolution. Infect Immun 61:2273–2276
     [Google Scholar]
  9. Buchanan S. K., Smith B. S., Venkatramani L., Xia D., Esser L., Palnitkar M., Chakraborty R., van der Helm D., Deisenhofer J. 1999; Crystal structure of the outer membrane active transporter FepA from Escherichia coli . Nat Struct Biol 6:56–63
     [Google Scholar]
  10. Carson S. D. B., Klebba P. E., Newton S. M. C., Sparling P. F. 1999; Ferric enterobactin binding and utilisation by Neisseria gonorrhoeae . J Bacteriol 181:2895–2901
     [Google Scholar]
  11. Carson S. D. B., Stone B., Beucher M., Fu J., Sparling P. F. 2000; Phase variation of the gonococcal siderophore receptor FetA. Mol Microbiol 36:585–593
     [Google Scholar]
  12. Claassen I., Meylis J., van der Ley P. 9 other authors 1996; Production, characterization and control of a Neisseria meningitidis hexavalent class 1 outer membrane protein containing vesicle vaccine. Vaccine 14:1001–1008
     [Google Scholar]
  13. Embley T. M. 1991; The linear PCR reaction: a simple and robust method for sequencing amplified rRNA genes. Lett Appl Microbiol 13:171–174
     [Google Scholar]
  14. Finne J., Leinonen M., Makela P. H. 1983; Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet 2:355–357
     [Google Scholar]
  15. Frasch C. E., van Alphen L., Poolman J. T., Rosenqvist E. 2001; Outer membrane protein vesicle vaccines for meningococcal disease. In Meningococcal Vaccines pp  81–108 Edited by Pollard A. J., Maiden M. C. J. Totowa, NJ: Humana;
     [Google Scholar]
  16. Fredriksen J. H., Rosenqvist E., Wedege E. 11 other authors 1991; Production, characterization and control of MenB-vaccine ‘Folkehelsa’: an outer membrane vesicle vaccine against group B meningococcal disease. Natl Inst Public Health Ann (Oslo) 14:67–79
     [Google Scholar]
  17. Gotschlich E. C., Goldschneider I., Artenstein M. S. 1969; Human immunity to the meningococcus IV. Immunogenicity of group A and group C meningococcal polysaccharides. J Exp Med 129:1367–1384
     [Google Scholar]
  18. Gotschlich E. C., Cornelissen C., Hill S. A. 9 other authors 1991; The mechanisms of genetic variation of gonococcal pili. Iron inducible proteins of Neisseria . A consensus. In Neisseriae 1990: Proceedings of the Seventh International Pathogenic Neisseria Conference pp  405–414 Edited by Achtman M., Kohl P., Marchal C., Morelli G., Seiler A., Thiesen B. Berlin: Walter de Gruyter;
     [Google Scholar]
  19. Huson D. H. 1998; splitstree: analyzing and visualizing evolutionary data. Bioinformatics 14:68–73
     [Google Scholar]
  20. Jennings H. J., Lugowski C. 1981; Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates. J Immunol 127:1011–1018
     [Google Scholar]
  21. Kumar S., Tamura K., Nei M. 1994; mega: molecular evolutionary genetics analysis software for microcomputers. Comput Appl Biosci 10:189–191
     [Google Scholar]
  22. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
     [Google Scholar]
  23. Maiden M. C. J., Suker J., McKenna A. J., Bygraves J. A., Feavers I. M. 1991; Comparison of the class 1 outer membrane proteins of eight serological reference strains of Neisseria meningitidis . Mol Microbiol 5:727–736
     [Google Scholar]
  24. Maiden M. C. J., Bygraves J. A., Feil E. 10 other authors 1998; Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95:3140–3145
     [Google Scholar]
  25. Martin S. L., Borrow R., van der Ley P., Dawson M., Fox A. J., Cartwright K. A. V. 2000; Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine. Vaccine 18:2476–2481
     [Google Scholar]
  26. Maskell D., Frankel G., Dougan G. 1993; Phase and antigenic variation – the impact on strategies for bacterial vaccine design. Trends Biotechnol 11:506–510
     [Google Scholar]
  27. McGuinness B., Barlow A. K., Clarke I. N., Farley J. E., Anilionis A., Poolman J. T., Heckels J. E. 1990; Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis . Synthetic peptides define the epitopes responsible for serosubtype specificity. J Exp Med 171:1871–1882
     [Google Scholar]
  28. McGuinness B. T., Lambden P. R., Heckels J. E. 1993; Class 1 outer membrane protein of Neisseria meningitidis : epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology. Mol Microbiol 7:505–514
     [Google Scholar]
  29. Nei M., Gojobori T. 1986; Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426
     [Google Scholar]
  30. Newton S. M., Igo J. D., Scott D. C., Klebba P. E. 1999; Effect of loop deletions on the binding and transport of ferric enterobactin by FepA. Mol Microbiol 32:1153–1165
     [Google Scholar]
  31. Pettersson A., Kuipers B., Pelzer M., Verhagen E., Tiesjema R. H., Tommassen J., Poolman J. T. 1990; Monoclonal antibodies against the 70-kilodalton iron-regulated protein of Neisseria meningitidis are bactericidal and strain specific. Infect Immun 58:3036–3041
     [Google Scholar]
  32. Pettersson A., Maas A., van Wassenaar D., van der Ley P., Tommassen J. 1995; Molecular characterization of FrpB, the 70-kilodalton iron-regulated outer membrane protein of Neisseria meningitidis . Infect Immun 63:4181–4184
     [Google Scholar]
  33. Pollard A. J., Levin M. 2000; Vaccines for prevention of meningococcal disease. Pediatr Infect Dis J 19:333–345
     [Google Scholar]
  34. Pollard A. J., Maiden M. C. J. 2001; Meningococcal vaccines. In Methods in Molecular Medicine Edited by Walker J. M. Totowa, NJ: Humana;
     [Google Scholar]
  35. Prinz T., Tommassen J. 2000; Association of iron-regulated outer membrane proteins of Neisseria meningitidis with the RmpM (class 4) protein. FEMS Microbiol Lett 183:49–53
     [Google Scholar]
  36. Reingold A. L., Broome C. V., Hightower A. W. 7 other authors 1985; Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet ii114–118
     [Google Scholar]
  37. Robertson B. D., Meyer T. F. 1992; Genetic variation in bacterial pathogens. In Molecular Biology of Bacterial Infection (Society for General Microbiology Symposium no. 49) pp  61–74 Edited by Hormaeche C. E., Penn C. W., Smyth C. J. Cambridge: Cambridge University Press;
     [Google Scholar]
  38. Rosenqvist E., Arne Høiby E., Wedege E., Bryn K., Kolberg J., Klem A., Rønnild E., Bjune G., Nøkleby H. 1995; Human antibody responses to meningococcal outer membrane antigens after three doses of the Norwegian group B meningococcal vaccine. Infect Immun 63:4642–4652
     [Google Scholar]
  39. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  40. Saukkonen K., Abdillahi H., Poolman J. T., Leinonen M. 1987; Protective efficacy of monoclonal antibodies to class 1 and class 3 outer membrane proteins of Neisseria meningitidis B: 15 : P1.16 in infant rat infection model: new prospects for vaccine development. Microb Pathogen 3:261–267
     [Google Scholar]
  41. Schryvers A. B., Stojiljkovic I. 1999; Iron acquisition systems in the pathogenic Neisseria . Mol Microbiol 32:1117–1123
     [Google Scholar]
  42. Scott D. C., Cao Z., Qi Z., Bauler M., Igo J. D., Newton S. M. C., Klebba P. E. 2001; Exchangeability of N termini in the ligand-gated porins of Escherichia coli . J Biol Chem 276:13025–13033
     [Google Scholar]
  43. Staden R. 1996; The staden sequence analysis package. Mol Biotechnol 5:233–241
     [Google Scholar]
  44. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76:4350–4354
     [Google Scholar]
  45. van der Ende A., Hopman C. T. P., Dankert J. 2000; Multiple mechanisms of phase variation of PorA in Neisseria meningitidis . Infect Immun 68:6685–6690
     [Google Scholar]
  46. van der Ley P., Poolman J. T. 1992; Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. Infect Immun 60:3156–3161
     [Google Scholar]
  47. van der Ley P., van der Biezen J., Sutmuller R., Hoogerhout P., Poolman J. T. 1996; Sequence variability of FrpB, a major iron-regulated outer-membrane protein in the pathogenic neisseriae. Microbiology 142:3269–3274
     [Google Scholar]
  48. Wedege E., Høiby E. A., Rosenqvist E., Bjune G. 1998; Immune responses against major outer membrane antigens of Neisseria meningitidis in vaccinees and controls who contracted meningococcal disease during the Norwegian serogroup B protection trial. Infect Immun 66:3223–3231
     [Google Scholar]
  49. Witholt B., Boekhout M., Brock M., Kingma J., van Heerikhuizen H., de Leij L. 1976; An efficient and reproducible procedure for the formation of spheroplasts from variously grown Escherichia coli . Anal Biochem 74:160–170
     [Google Scholar]
  50. Womble D. D. 2000; GCG: The Wisconsin Package of sequence analysis programs. Methods Mol Biol 132:3–22
     [Google Scholar]
  51. Wyle F. A., Artenstein M. S., Brandt B. L., Tramont E. C., Kasper D. L., Altieri P. L., Berman S. L., Lowenthal J. P. 1972; Immunologic response of man to group B meningococcal polysaccharide vaccines. J Infect Dis 126:514–521
     [Google Scholar]
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Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component
Microbiology 149, 1849 (2003); https://doi.org/10.1099/mic.0.26131-0
/content/journal/micro/10.1099/mic.0.26131-0
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