1887

Abstract

The meningococcal NMB0035 locus encodes a 47 kDa outer-membrane protein that is highly conserved antigenically, and is able to induce antibodies during infection and bactericidal responses . This study analysed the surface exposure of this protein using specific antibodies in flow cytometry assays and determined its nucleotide sequence in 33 strains. Genomic analyses revealed no significant differences in the nucleotide or amino acid sequences, but flow cytometry showed that surface accessibility was highly variable among the strains. These results suggest that masking by and/or association with lipo-oligosaccharides or other membrane molecules can be crucial for antigen accessibility, which must be thoroughly analysed in new vaccine candidates.

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2008-01-01
2024-12-14
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References

  1. Adu-Bobie J., Capecchi B., Senisto D., Rappouli R., Pizza M. 2003; Two years into reverse vaccinology. Vaccine 21:605–610 [CrossRef]
    [Google Scholar]
  2. Arenas J. A., Abel A., Sánchez S., Alcalá B., Criado M. T., Ferreirós C. M. 2006; Locus NMB0035 codes for a 47 kDa surface-accessible conserved antigen in Neisseria . Int Microbiol 9:273–280
    [Google Scholar]
  3. Beitz E. 2000; TeXshade: shading and labeling of multiple sequence alignment using LaTeX2e. Bioinformatics 16:135–139 [CrossRef]
    [Google Scholar]
  4. Bowden R. A., Cloeckaert A., Zygmunt M. S., Bernard S., Dubray G. 1995; Surface exposure of outer membrane protein and lipopolysaccharide epitopes in Brucella species studied by enzyme-linked immunosorbent assay and flow cytometry. Infect Immun 63:3945–3952
    [Google Scholar]
  5. Doytchinova I. A., Flower D. R. 2002; Quantitative approaches to computational vaccinology. Immunol Cell Biol 80:270–279 [CrossRef]
    [Google Scholar]
  6. Gorringe A. R., Halliwell D., Matheson M., Reddin K., Finney M., Hudson M. 2005; The development of a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles. Vaccine 23:2210–2213 [CrossRef]
    [Google Scholar]
  7. Gorter A. D., Oostrikb J., van der Ley P., Hiemstrac P. S., Dankerta J., van Alphen L. 2003; Involvement of lipooligosaccharides of Haemophilus influenzae and Neisseria meningitidis in defensin-enhanced bacterial adherence to epithelial cells. Microb Pathog 34:121–130 [CrossRef]
    [Google Scholar]
  8. Huang X., Madan A. 1999; cap3: a DNA sequence assembly program. Genome Res 9:868–877 [CrossRef]
    [Google Scholar]
  9. Jolley K. A., Appleby L., Wright J. C., Christoloulides M., Heckels J. E. 2001; Immunization with recombinant Opc outer membrane protein from Neisseria meningitidis : influence of sequence variation and levels of expression on the bactericidal immune response against meningococci. Infect Immun 69:3809–3816 [CrossRef]
    [Google Scholar]
  10. Kahler C. M., Datta A., Tzeng Y. L., Carlson R. W., Stephens D. S. 2005; Inner core assembly and structure of the lipooligosaccharide of Neisseria meningitidis : capacity of strain NMB to express all known immunotype epitopes. Glycobiology 15:409–419
    [Google Scholar]
  11. Khan A. S., Mujer C. V., Alefantis T. G., Connolly J. P., Mayr V. B., Walcher P., Lubilz W., DelVecchio U. G. 2006; Proteomics and bioinformatics strategies to design countermeasures against infectious threat agents. J Chem Inf Model 46:111–115 [CrossRef]
    [Google Scholar]
  12. Kumar S., Tamura K., Nei M. 2004; mega3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163 [CrossRef]
    [Google Scholar]
  13. Leclerc C. L. 2003; New approaches in vaccine development. Comp Immunol Microbiol Infect Dis 26:329–341 [CrossRef]
    [Google Scholar]
  14. Martin S. L., Borrow R., van der Ley P., Dawson M., Fox A. J., Cartwright K. A. 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 [CrossRef]
    [Google Scholar]
  15. Michaelsen T. E., Aase A., Kolberg J., Wedege E., Rosenqvist E. 2001; PorB3 outer membrane protein on Neisseria meningitidis is poorly accessible for antibody binding on live bacteria. Vaccine 19:1526–1533 [CrossRef]
    [Google Scholar]
  16. Morley S. L., Pollard A. J. 2001; Vaccine prevention of meningococcal disease, coming soon?. Vaccine 20:666–687 [CrossRef]
    [Google Scholar]
  17. Morley S. L., Cole M. J., Ison C. A., Camaraza M. A., Sotolongo M., Anwar N., Cuevas I., Carbonero M., Campa H. C. other authors 2001; Immunogenicity of a serogroup B meningococcal vaccine against multiple Neisseria meningitidis strains in infants. Pediatr Infect Dis J 20:1054–1061 [CrossRef]
    [Google Scholar]
  18. O'Dwyer C. A., Reddin K., Martin D., Taylor S. C., Gorringe A. R., Hudson M. J., Brodeur B. R., Langford P. R., Kroll J. S. 2004; Expression of heterologous antigens in commensal Neisseria spp.: preservation of conformational epitopes with vaccine potential. Infect Immun 72:6511–6518 [CrossRef]
    [Google Scholar]
  19. Petrovsky N., Brusic V. 2002; Computational immunology: the coming of age. Immunol Cell Biol 80:248–254 [CrossRef]
    [Google Scholar]
  20. Pintor M., Ferrón L., Gómez J. A., Powell N. B. L., Ala'Aldeen D. A. A., Borrriello S. P., Criado M. T., Ferreirós C. M. 1996; Blocking of iron uptake from transferrin by antibodies against the transferrin binding proteins in Neisseria meningitidis . Microb Pathog 20:127–139 [CrossRef]
    [Google Scholar]
  21. Rosenqvist E., Hoiby E. A., Wedege E., Bryn K., Kolberg J., Klem A., Ronnild E., Bjune G., Nokleby 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]
  22. Steeghs L., de Cock H., Evers E., Zomer B., Tommassen J., van der Ley P. 2001; Outer membrane composition of a lipopolysaccharide-deficient Neisseria meningitidis mutant. EMBO J 20:6937–6945 [CrossRef]
    [Google Scholar]
  23. Tappero J. W., Lagos R., Ballesteros A. M., Plikaytis B., Williams D., Dykes J., Gheesling L. L., Carlone G. M., Hoiby E. A. other authors 1999; Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile. JAMA 281:1520–1527
    [Google Scholar]
  24. Troncoso G., Sánchez S., Moreda M., Criado M. T., Ferreirós C. M. 2000; Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species. FEMS Immunol Med Microbiol 27:103–109 [CrossRef]
    [Google Scholar]
  25. Valdivia R. H., Falkow S. 1998; Flow cytometry and bacterial pathogenesis. Curr Opin Microbiol 1:359–363 [CrossRef]
    [Google Scholar]
  26. Van de Peer Y., De Wachter R. 1994; treecon for Windows: a software package for the construction and drawing of evolutionary trees for the Microsoft Windows environment. Comput Appl Biosci 10:569–570
    [Google Scholar]
  27. Welsch J. A., Moe G. R., Rossi R., Adu-Bobie J., Rappouli R., Granoff D. M. 2003; Antibody to genome-derived neisserial antigen 2132, a Neisseria meningitidis candidate vaccine, confers protection against bacteremia in the absence of complement-mediated bactericidal activity. J Infect Dis 188:1730–1740 [CrossRef]
    [Google Scholar]
  28. Williams J. N., Skipp P. J., Humphries H. E., Christodoulides M., O'Connor C. D., Heckels J. E. 2007; Proteomic analysis of outer membranes and vesicles from wild-type serogroup B Neisseria meningitidis and a lipopolysaccharide-deficient mutant. Infect Immun 75:1364–1372 [CrossRef]
    [Google Scholar]
  29. Yu K., Petrovsky Y. K., Schönbach C., Koh J. Y., Brusic V. 2002; Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med 8:137–148
    [Google Scholar]
  30. Zagursky R. J., Rusell D. 2001; Bioinformatics: use in bacterial vaccine discovery. Biotechniques 31:636–640
    [Google Scholar]
  31. Zhang C., Anderson A., DeLisi C. 1998; Structural principles that govern the peptide-binding motifs of class I MHC molecules. J Mol Biol 281:929–947 [CrossRef]
    [Google Scholar]
  32. Zhu P., Klutch M. J., Bash M. C., Tsang R. S. W., Ng L., Tsai C. 2002; Genetic diversity of three lgt loci for biosynthesis of lipooligosaccharide (LOS) in Neisseria species. Microbiology 148:1833–1844
    [Google Scholar]
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