1887

Abstract

The significance of serogroup B membrane proteins as vaccine candidates is continually growing. Here, we studied different aspects of antigen NMB0088, a protein that is abundant in outer-membrane vesicle preparations and is thought to be a surface protein. The gene encoding protein NMB0088 was sequenced in a panel of 34 different meningococcal strains with clinical and epidemiological relevance. After this analysis, four variants of NMB0088 were identified; the variability was confined to three specific segments, designated VR1, VR2 and VR3. Secondary structure predictions, refined with alignment analysis and homology modelling using FadL of , revealed that almost all the variable regions were located in extracellular loop domains. In addition, the NMB0088 antigen was expressed in and a procedure for obtaining purified recombinant NMB0088 is described. The humoral immune response elicited in BALB/c mice was measured by ELISA and Western blotting, while the functional activity of these antibodies was determined in a serum bactericidal assay and an animal protection model. After immunization in mice, the recombinant protein was capable of inducing a protective response when it was administered inserted into liposomes. According to our results, the recombinant NMB0088 protein may represent a novel antigen for a vaccine against meningococcal disease. However, results from the variability study should be considered for designing a cross-protective formulation in future studies.

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2009-02-01
2024-03-28
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References

  1. 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 [CrossRef]
    [Google Scholar]
  2. Bjune G., Hoiby E. A., Gronnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H. other authors 1991; Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338:1093–1096 [CrossRef]
    [Google Scholar]
  3. Black P. N., Said B., Ghosn C. R., Beach J. V., Nunn W. D. 1987; Purification and characterization of an outer membrane-bound protein involved in long-chain fatty acid transport in Escherichia coli . J Biol Chem 262:1412–1419
    [Google Scholar]
  4. Bolduc G. R., Bouchet V., Jiang R. Z., Geisselsoder J., Truong-Bolduc Q. C., Rice P. A., Pelton S. I., Goldstein R. 2000; Variability of outer membrane protein P1 and its evaluation as a vaccine candidate against experimental otitis media due to nontypeable Haemophilus influenzae : an unambiguous, multifaceted approach. Infect Immun 68:4505–4517 [CrossRef]
    [Google Scholar]
  5. Buchanan S. K. 1999; Beta-barrel proteins from bacterial outer membranes: structure, function and refolding. Curr Opin Struct Biol 9:455–461 [CrossRef]
    [Google Scholar]
  6. Buisine N., Tang C. M., Chalmers R. 2002; Transposon-like Correia elements: structure, distribution and genetic exchange between pathogenic Neisseria sp. FEBS Lett 522:52–58 [CrossRef]
    [Google Scholar]
  7. Christodoulides M., Brooks J. L., Rattue E., Heckels J. E. 1998; Immunization with recombinant class 1 outer-membrane protein from Neisseria meningitidis : influence of liposomes and adjuvants on antibody avidity, recognition of native protein and the induction of a bactericidal immune response against meningococci. Microbiology 144:3027–3037 [CrossRef]
    [Google Scholar]
  8. Comanducci M., Bambini S., Brunelli B., Adu-Bobie J., Aricò B., Capecchi B., Giuliani M. M., Masignani V., Santini L. other authors 2002; NadA, a novel vaccine candidate of Neisseria meningitidis . J Exp Med 195:1445–1454 [CrossRef]
    [Google Scholar]
  9. De Gregorio E., Abrescia C., Carlomagno M. S., Di Nocera P. P. 2003a; Asymmetrical distribution of Neisseria miniature insertion sequence DNA repeats among pathogenic and nonpathogenic Neisseria strains. Infect Immun 71:4217–4221 [CrossRef]
    [Google Scholar]
  10. De Gregorio E., Abrescia C., Carlomagno M. S., Di Nocera P. P. 2003b; Ribonuclease III-mediated processing of specific Neisseria meningitidis mRNAs. Biochem J 374:799–805 [CrossRef]
    [Google Scholar]
  11. Delgado M., Yero D., Niebla O., González S., Climent Y., Pérez Y., Cobas K., Caballero E., García D., Pajón R. 2007; Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate. Vaccine 25:8420–8431 [CrossRef]
    [Google Scholar]
  12. Derrick J. P., Urwin R., Suker J., Feavers I. M., Maiden M. C. 1999; Structural and evolutionary inference from molecular variation in Neisseria porins. Infect Immun 67:2406–2413
    [Google Scholar]
  13. 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]
  14. Francis F., Ramirez-Arcos S., Salimnia H., Victor C., Dillon J. R. 2000; Organization and transcription of the division cell wall ( dcw ) cluster in Neisseria gonorrhoeae . Gene 251:141–151 [CrossRef]
    [Google Scholar]
  15. Fredriksen J. H., Rosenqvist E., Wedege E., Bryn K., Bjune G., Frøholm L. O., Lindbak A. K., Møgster B., Namork E. other authors 1991; Production, characterization and control of MenB-vaccine “Folkehelsa”: an outer membrane vesicle vaccine against group B meningococcal disease. NIPH Ann 14:67–79
    [Google Scholar]
  16. Fu D., Libson A., Miercke L. J., Weitzman C., Nollert P., Krucinski J., Stroud R. M. 2000; Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290:481–486 [CrossRef]
    [Google Scholar]
  17. Giuliani M. M., Adu-Bobie J., Comanducci M., Aricò B., Savino S., Santini L., Brunelli B., Bambini S., Biolchi A. other authors 2006; A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci U S A 103:10834–10839 [CrossRef]
    [Google Scholar]
  18. Gorringe A., 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]
  19. Hearn E. M., Patel D. R., van den Berg B. 2008; Outer-membrane transport of aromatic hydrocarbons as a first step in biodegradation. Proc Natl Acad Sci U S A 105:8601–8606 [CrossRef]
    [Google Scholar]
  20. Hsu C. A., Lin W. R., Li J. C., Liu Y. L., Tseng Y. T., Chang C. M., Lee Y. S., Yang C. Y. 2008; Immunoproteomic identification of the hypothetical protein NMB1468 as a novel lipoprotein ubiquitous in Neisseria meningitidis with vaccine potential. Proteomics 8:2115–2125 [CrossRef]
    [Google Scholar]
  21. Jodar L., Feavers I. M., Salisbury D., Granoff D. M. 2002; Development of vaccines against meningococcal disease. Lancet 359:1499–1508 [CrossRef]
    [Google Scholar]
  22. Kirby C., Gregoriadis G. 1984; Dehydration rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Biotechnology 2:979–984 [CrossRef]
    [Google Scholar]
  23. 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 [CrossRef]
    [Google Scholar]
  24. Liu S. V., Saunders N. J., Jeffries A., Rest R. F. 2002; Genome analysis and strain comparison of Correia repeats and Correia repeat-enclosed elements in pathogenic Neisseria . J Bacteriol 184:6163–6173 [CrossRef]
    [Google Scholar]
  25. Martin D., Cadieux N., Hamel J., Brodeur B. R. 1997; Highly conserved Neisseria meningitidis surface protein confers protection against experimental infection. J Exp Med 185:1173–1183 [CrossRef]
    [Google Scholar]
  26. 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]
  27. Maslanka S. E., Gheesling L. L., Libutti D. E., Donaldson K. B., Harakeh H. S., Dykes J. K., Arhin F. F., Devi S. J., Frasch C. E. other authors 1997; Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group. Clin Diagn Lab Immunol 4:156–167
    [Google Scholar]
  28. Mes T. H., van Putten J. P. 2007; Positively selected codons in immune-exposed loops of the vaccine candidate OMP-P1 of Haemophilus influenzae . J Mol Evol 64:411–422 [CrossRef]
    [Google Scholar]
  29. Mitka M. 2005; New vaccine should ease meningitis fears. JAMA 293:1433–1434 [CrossRef]
    [Google Scholar]
  30. Mora M., Veggi D., Santini L., Pizza M., Rappuoli R. 2003; Reverse vaccinology. Drug Discov Today 8:459–464 [CrossRef]
    [Google Scholar]
  31. Munson R. Jr, Hunt A. 1989; Isolation and characterization of a mutant of Haemophilus influenzae type b deficient in outer membrane protein P1. Infect Immun 57:1002–1004
    [Google Scholar]
  32. Murphy T. F., Brauer A. L., Yuskiw N., McNamara E. R., Kirkham C. 2001; Conservation of outer membrane protein E among strains of Moraxella catarrhalis . Infect Immun 69:3576–3580 [CrossRef]
    [Google Scholar]
  33. Nally J. E., Whitelegge J. P., Aguilera R., Pereira M. M., Blanco D. R., Lovett M. A. 2005; Purification and proteomic analysis of outer membrane vesicles from a clinical isolate of Leptospira interrogans serovar Copenhageni. Proteomics 5:144–152 [CrossRef]
    [Google Scholar]
  34. Niebla O., Alvarez A., Martin A., Rodriguez A., Delgado M., Falcon V., Guillen G. 2001; Immunogenicity of recombinant class 1 protein from Neisseria meningitidis refolded into phospholipid vesicles and detergent. Vaccine 19:3568–3574 [CrossRef]
    [Google Scholar]
  35. Peng J., Yang L., Yang F., Yang J., Yan Y., Nie H., Zhang X., Xiong Z., Jiang Y. other authors 2008; Characterization of ST-4821 complex, a unique Neisseria meningitidis clone. Genomics 91:78–87 [CrossRef]
    [Google Scholar]
  36. Pizza M., Scarlato V., Masignani V., Giuliani M. M., Aricò B., Comanducci M., Jennings G. T., Baldi L., Bartolini E. other authors 2000; Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287:1816–1820 [CrossRef]
    [Google Scholar]
  37. Rosenqvist E., Wedege E., Hoiby E. A., Froholm L. O. 1990; Serogroup determination of Neisseria meningitidis by whole-cell ELISA, dot-blotting and agglutination. APMIS 98:501–506 [CrossRef]
    [Google Scholar]
  38. Rosenstein N. E., Perkins B. A., Stephens D. S., Popovic T., Hughes J. M. 2001; Meningococcal disease. N Engl J Med 344:1378–1388 [CrossRef]
    [Google Scholar]
  39. Sardinas G., Reddin K., Pajon R., Gorringe A. 2006; Outer membrane vesicles of Neisseria lactamica as a potential mucosal adjuvant. Vaccine 24:206–214 [CrossRef]
    [Google Scholar]
  40. Schulz G. E. 2000; beta-Barrel membrane proteins. Curr Opin Struct Biol 10:443–447 [CrossRef]
    [Google Scholar]
  41. Sierra G. V., Campa H. C., Varcacel N. M., Garcia I. L., Izquierdo P. L., Sotolongo P. F., Casanueva G. V., Rico C. O., Rodriguez C. R., Terry M. H. 1991; Vaccine against group B Neisseria meningitidis : protection trial and mass vaccination results in Cuba. NIPH Ann 14:195–207
    [Google Scholar]
  42. Tappero J. W., Lagos R., Ballesteros A. M., Plikaytis B., Williams D., Dykes J., Gheesling L. L., Carlone G. M., Høiby 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]
  43. Tettelin H., Saunders N. J., Heidelberg J., Jeffries A. C., Nelson K. E., Eisen J. A., Ketchum K. A., Hood D. W., Peden J. F. other authors 2000; Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287:1809–1815 [CrossRef]
    [Google Scholar]
  44. Uli L., Castellanos-Serra L., Betancourt L., Dominguez F., Barbera R., Sotolongo F., Guillen G., Pajon F. R. 2006; Outer membrane vesicles of the VA-MENGOC-BC(R) vaccine against serogroup B of Neisseria meningitidis : analysis of protein components by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 6:3389–3399 [CrossRef]
    [Google Scholar]
  45. van den Berg B., Black P. N., Clemons W. M. Jr, Rapoport T. A. 2004; Crystal structure of the long-chain fatty acid transporter FadL. Science 304:1506–1509 [CrossRef]
    [Google Scholar]
  46. van der Ley P., Heckels J. E., Virji M., Hoogerhout P., Poolman J. T. 1991; Topology of outer membrane porins in pathogenic Neisseria spp. Infect Immun 59:2963–2971
    [Google Scholar]
  47. Vaughan T. E., Skipp P. J., O'Connor C. D., Hudson M. J., Vipond R., Elmore M. J., Gorringe A. R. 2006; Proteomic analysis of Neisseria lactamica and Neisseria meningitidis outer membrane vesicle vaccine antigens. Vaccine 24:5277–5293 [CrossRef]
    [Google Scholar]
  48. Vipond C., Suker J., Jones C., Tang C., Feavers I. M., Wheeler J. X. 2006; Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared from the group B strain NZ98/254. Proteomics 6:3400–3413 [CrossRef]
    [Google Scholar]
  49. Wedege E., Froholm L. O. 1986; Human antibody response to a group B serotype 2a meningococcal vaccine determined by immunoblotting. Infect Immun 51:571–578
    [Google Scholar]
  50. Wheeler J. X., Vipond C., Feavers I. M. 2007; Exploring the proteome of meningococcal outer membrane vesicle vaccines. Proteomics Clin Appl 1:1198–1210 [CrossRef]
    [Google Scholar]
  51. 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]
  52. Wright J. C., Williams J. N., Christodoulides M., Heckels J. E. 2002; Immunization with the recombinant PorB outer membrane protein induces a bactericidal immune response against Neisseria meningitidis . Infect Immun 70:4028–4034 [CrossRef]
    [Google Scholar]
  53. Yau W. M., Wimley W. C., Gawrisch K., White S. H. 1998; The preference of tryptophan for membrane interfaces. Biochemistry 37:14713–14718 [CrossRef]
    [Google Scholar]
  54. Yero C. D., Pajon F. R., Caballero M. E., Cobas A. K., Lopez H. Y., Farinas M. M., Gonzales B. S., Acosta D. A. 2005; Immunization of mice with Neisseria meningitidis serogroup B genomic expression libraries elicits functional antibodies and reduces the level of bacteremia in an infant rat infection model. Vaccine 23:932–939 [CrossRef]
    [Google Scholar]
  55. Yero D., Pajon R., Niebla O., Sardinas G., Vivar I., Perera Y., Garcia D., Delgado M., Cobas K. 2006; Bicistronic expression plasmid for the rapid production of recombinant fused proteins in Escherichia coli . Biotechnol Appl Biochem 44:27–34 [CrossRef]
    [Google Scholar]
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