1887

Abstract

Meningococcal factor H binding protein (fHbp) is a promising vaccine antigen that binds the human complement downregulatory molecule factor H (fH), and this binding enhances the survival of the organism in serum. Based on sequence variability of the entire protein, fHbp has been divided into three variant groups or two subfamilies. Here, we present evidence based on phylogenetic analysis of 70 unique fHbp amino acid sequences that the molecular architecture is modular. From sequences of natural chimeras we identified blocks of two to five invariant residues that flanked five modular variable segments. Although overall, 46 % of the fHbp amino acids were invariant, based on a crystal structure, the invariant blocks that flanked the modular variable segments clustered on the membrane surface containing the amino-terminal lipid anchor, while the remaining invariant residues were located throughout the protein. Each of the five modular variable segments could be classified into one of two types, designated or , based on homology with segments encoded by variant 1 or 3 fHbp genes, respectively. Forty of the fHbps (57 %) comprised only (=33) or (=7) type segments. The remaining 30 proteins (43 %) were chimeras and could be classified into one of four modular groups. These included all 15 proteins assigned to the previously described variant 2 in subfamily A. The modular segments of one chimeric modular group had 96 % amino acid identity with those of fHbp orthologs in . Collectively, the data suggest that recombination between and progenitors generated a family of modular, antigenically diverse meningococcal fHbps.

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2009-09-01
2024-03-28
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References

  1. Arreaza L., Alcala B., Salcedo C., de la Fuente L., Vazquez J. A. 2003; Dynamics of the penA gene in serogroup C meningococcal strains. J Infect Dis 187:1010–1014
    [Google Scholar]
  2. Bambini S., Muzzi A., Olcen P., Rappuoli R., Pizza M., Comanducci M. 2009; Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus. Vaccine 27:2794–2803
    [Google Scholar]
  3. Beernink P. T., Granoff D. M. 2008; Bactericidal antibody responses induced by meningococcal recombinant chimeric factor H-binding protein vaccines. Infect Immun 76:2568–2575
    [Google Scholar]
  4. Beernink P. T., Welsch J. A., Harrison L. H., Leipus A., Kaplan S. L., Granoff D. M. 2007; Prevalence of factor H-binding protein variants and NadA among meningococcal group B isolates from the United States: implications for the development of a multicomponent group B vaccine. J Infect Dis 195:1472–1479
    [Google Scholar]
  5. Beernink P. T., Welsch J. A., Bar-Lev M., Koeberling O., Comanducci M., Granoff D. M. 2008; Fine antigenic specificity and cooperative bactericidal activity of monoclonal antibodies directed at the meningococcal vaccine candidate, factor H-binding protein. Infect Immun 76:4232–4240
    [Google Scholar]
  6. Beernink P. T., Caugant D. A., Welsch J. A., Koeberling O., Granoff D. M. 2009a; Meningococcal factor H-binding protein variants expressed by epidemic capsular group A, W-135, and X strains from Africa. J Infect Dis 199:1360–1368
    [Google Scholar]
  7. Beernink P. T., Lopasso C., Angiolillo A., Felici F., Granoff D. 2009b; A region of the N-terminal domain of meningococcal factor H-binding protein that elicits bactericidal antibody across antigenic variant groups. Mol Immunol 46:1647–1653
    [Google Scholar]
  8. Bentley S. D., Vernikos G. S., Snyder L. A., Churcher C., Arrowsmith C., Chillingworth T., Cronin A., Davis P. H., Holroyd N. E. other authors 2007; Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet 3:e23
    [Google Scholar]
  9. Bilek N., Ison C. A., Spratt B. G. 2009; Relative contributions of recombination and mutation to the diversification of the opa gene repertoire of Neisseria gonorrhoeae . J Bacteriol 191:1878–1890
    [Google Scholar]
  10. Callaghan M. J., Buckee C. O., Jolley K. A., Kriz P., Maiden M. C., Gupta S. 2008; The effect of immune selection on the structure of the meningococcal Opa protein repertoire. PLoS Pathog 4:e1000020
    [Google Scholar]
  11. Castresana J. 2000; Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17:540–552
    [Google Scholar]
  12. Dereeper A., Guignon V., Blanc G., Audic S., Buffet S., Chevenet F., Dufayard J. F., Guindon S., Lefort V. other authors 2008; Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36:W465–W469
    [Google Scholar]
  13. Edgar R. C. 2004; muscle: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797
    [Google Scholar]
  14. Fletcher L. D., Bernfield L., Barniak V., Farley J. E., Howell A., Knauf M., Ooi P., Smith R. P., Weise P. other authors 2004; Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun 72:2088–2100
    [Google Scholar]
  15. Giuliani M. M., Santini L., Brunelli B., Biolchi A., Aricò B., Di Marcello F., Cartocci E., Comanducci M., Masignani V. other authors 2005; The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun 73:1151–1160
    [Google Scholar]
  16. Granoff D. M., Welsch J. A., Ram S. 2009; Binding of complement factor H (fH) to Neisseria meningitidis is specific for human fH and inhibits complement activation by rat and rabbit sera. Infect Immun 77:764–769
    [Google Scholar]
  17. Guindon S., Gascuel O. 2003; A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704
    [Google Scholar]
  18. Hotopp J. C., Grifantini R., Kumar N., Tzeng Y. L., Fouts D., Frigimelica E., Draghi M., Giuliani M. M., Rappuoli R. other authors 2006; Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen-specific genes. Microbiology 152:3733–3749
    [Google Scholar]
  19. Jacobsson S., Hedberg S. T., Molling P., Unemo M., Comanducci M., Rappuoli R., Olcen P. 2009; Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease. Vaccine 27:1579–1584
    [Google Scholar]
  20. Jansen K. U., McNeil L. K., Dragalin V., Anderson A. S., Hoiseth S. K., Arora A., Emini E. E., Zlotnick G. W., Jones T. 2008 Bivalent recombinant LP2086 vaccine to provide broad protection against Neisseria meningitidis B disease: immunological correlates of protection and how to assess coverage against invasive MnB strains.Abstract number 064 in 16th International Pathogenic Neisseria Conference Rotterdam, The Netherlands: September 7–12 2008 Edited by van Alphen L., van der Ley P., van den Dobbelsteen G. ()
    [Google Scholar]
  21. Larkin M. A., Blackshields G., Brown N. P., Chenna R., McGettigan P. A., McWilliam H., Valentin F., Wallace I. M., Wilm A. & other authors; 2007; clustal w and clustal_x version 2.0. Bioinformatics 23:2947–2948
    [Google Scholar]
  22. Madico G., Welsch J. A., Lewis L. A., McNaughton A., Perlman D. H., Costello C. E., Ngampasutadol J., Vogel U., Granoff D. M., Ram S. 2006; The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J Immunol 177:501–510
    [Google Scholar]
  23. Marshall H., Nissen M. D., Richmond P., Lambert S. B., Roberton D. M., Jones T., Lockhart S., Gruber W., Arona A. 2008 A randomized, placebo-controlled, double-blind, phase 1 trial of ascending doses of meningococcal group B rLP2086 vaccine in healthy adults. Abstract number P213 in 16th International Pathogenic Neisseria Conference Rotterdam, The Netherlands: September 7–12 2008 Edited by van Alphen L., van der Ley P., van den Dobbelsteen G. ()
    [Google Scholar]
  24. Masignani V., Comanducci M., Giuliani M. M., Bambini S., Adu-Bobie J., Arico B., Brunelli B., Pieri A., Santini L. other authors 2003; Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med 197:789–799
    [Google Scholar]
  25. Ochiai S., Ishiko H., Yasuda M., Deguchi T. 2008; Rapid detection of the mosaic structure of the Neisseria gonorrhoeae penA gene, which is associated with decreased susceptibilities to oral cephalosporins. J Clin Microbiol 46:1804–1810
    [Google Scholar]
  26. Plested J. S., Welsch J. A., Granoff D. M. 2009; Ex vivo model of meningococcal bacteremia using human blood for measuring vaccine-induced serum passive protective activity. Clin Vaccine Immunol 16:785–791
    [Google Scholar]
  27. Rappuoli R. 2008; The application of reverse vaccinology, Novartis MenB vaccine developed by design. Abstract number 065 in 16th International Pathogenic Neisseria Conference Rotterdam, The Netherlands: September 7–12 2008 Edited by van Alphen L., van der Ley P., van den Dobbelsteen G. ()
    [Google Scholar]
  28. Richmond P., Marshall H., Nissen M. D., Lambert S., Jones T., Gruber W., Arora A. 2008; A randomized, observer-blinded, active control, phase 1 trial of meningococcal serogroup B rLP2086 vaccine in healthy children and adolescents aged 8 to 14 years. Abstract number P2132 in 16th International Pathogenic Neisseria Conference Rotterdam, The Netherlands: September 7–12 2008 Edited by van Alphen L., van der Ley P., van den Dobbelsteen G. ()
    [Google Scholar]
  29. Rokbi B., Maitre-Wilmotte G., Mazarin V., Fourrichon L., Lissolo L., Quentin-Millet M. J. 1995; Variable sequences in a mosaic-like domain of meningococcal tbp2 encode immunoreactive epitopes. FEMS Microbiol Lett 132:277–283
    [Google Scholar]
  30. Scarselli M., Cantini F., Santini L., Veggi D., Dragonetti S., Donati C., Savino S., Giuliani M. M., Comanducci M. other authors 2009; Epitope mapping of a bactericidal monoclonal antibody against the factor H binding protein of Neisseria meningitidis . J Mol Biol 386:97–108
    [Google Scholar]
  31. Schneider M. C., Exley R. M., Chan H., Feavers I., Kang Y. H., Sim R. B., Tang C. M. 2006; Functional significance of factor H binding to Neisseria meningitidis . J Immunol 176:7566–7575
    [Google Scholar]
  32. Schneider M. C., Prosser B. E., Caesar J. J., Kugelberg E., Li S., Zhang Q., Quoraishi S., Lovett J. E., Deane J. E. other authors 2009; Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 458:890–893
    [Google Scholar]
  33. Snape M. D., Dawson T., Morant A., John B., Ohene-Kena R., Borrow R., Oster P., Pollard A. J. 2008; Immunogenicity and reactogenicity of a novel serogroup B Neisseria meningitidis vaccine administered from 6 months of age. Abstract number 069 in 16th International Pathogenic Neisseria Conference Rotterdam, The Netherlands: September 7–12 2008 Edited by van Alphen L., van. der Ley P., van den Dobbelsteen G. ()
    [Google Scholar]
  34. Szczesny P., Lupas A. 2008; Domain annotation of trimeric autotransporter adhesins – daTAA. Bioinformatics 24:1251–1256
    [Google Scholar]
  35. Tamura K., Dudley J., Nei M., Kumar S. 2007; mega4: Molecular Evolutionary Genetics Analysis (mega) software version 4.0. Mol Biol Evol 24:1596–1599
    [Google Scholar]
  36. Welsch J. A., Rossi R., Comanducci M., Granoff D. M. 2004; Protective activity of monoclonal antibodies to genome-derived neisserial antigen 1870, a Neisseria meningitidis candidate vaccine. J Immunol 172:5606–5615
    [Google Scholar]
  37. Welsch J. A., Ram S., Koeberling O., Granoff D. M. 2008; Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen. J Infect Dis 197:1053–1061
    [Google Scholar]
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