1887

Microbiology Society logo

Volume 142, Issue 9

Immune responses to linear epitopes on the PorB protein of Neisseria meningitidis in patients with systemic meningococcal disease Free

Abstract

Neisserial porins, the major protein constituents of the outer membrane capable of inducing antibody responses in humans, are considered to be meningococcal vaccine candidates, so it is important to map the relevant B-cell epitopes. For B-cell epitope analyses of the serotype 15 PorB protein in paired sera from selected patients with systemic meningococcal disease (SMD) were screened with synthetic 12mer peptides spanning the PorB protein sequence, and/or its variable region 1 (VR1). A ‘SMD-related’ linear B-cell epitope was found within the VR1 region consisting of 14 residues (svFHQNGQVTEvtt). A 23mer soluble peptide (D63b2) that covered the VR1 region, including the complete svFHQNGQVTEvtt sequence, was recognized, whereas no detectable binding was observed to a 16mer peptide (D63a1) containing most of the essential sequence (FHQNGQVTEvtt). A low frequency of lgG responses specific for the PorB linear epitopes was found in convalescent-phase sera from 132 SMD patients studied, as judged from both immunoblotting studies (24/132; 18·2%) and reactivity with peptide D63b2 (18/132; 13·6%). Peptide D63B2 significantly inhibited lgG binding to the denatured PorB protein on immunoblots, suggesting that this B-cell epitope was one of the main linear epitopes on the PorB protein recognized by sera from some SMD patients.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): B-cell epitope , Neisseria meningitidis , PorB protein , synthetic peptides and systemic meningococcal disease
© Society for General Microbiology 1996
Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-142-9-2491
1996-09-01
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/micro/142/9/mic-142-9-2491.html?itemId=/content/journal/micro/10.1099/00221287-142-9-2491&mimeType=html&fmt=ahah

References

  1. Achtman M., Neibert M., Crowe B. A., Strittmatter W., Kusecek B., Weyse E., Walsh M. J., Slawig B., Morelli G., Moll A., Blake M. 1988; Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A. J Exp Med 168:507–525
     [Google Scholar]
  2. Ada G. L. 1992; Vaccine antigens. In Structure of Antigens pp. 367–391 Van Regenmortel M. H. V. Edited by London:: CRC Press.;
     [Google Scholar]
  3. Ala´Aldeen D. A. A., Stevenson P., Griffiths E., Gorringe A. R., Irons L. I., Robinson A., Hyde S., Borriello S. P. 1994; Immune responses in humans and animals to meningococcal transferrinbinding proteins: implications for vaccine design. Infect Immun 62:2984–2990
     [Google Scholar]
  4. Aoun L, Lavitola A., Aubert G., Prère M. F., Cremieux A. C., Martin P. M. V. 1988; Human antibody response to the 70-kDa common neisserial antigen in patients and carriers of meningococci or non-pathogenic Neisseria . Ann Inst Pasteur Immunol 139:203–212
     [Google Scholar]
  5. Bash M. C., Lesiak K. B., Banks S. D., Frasch C. E. 1995; Analysis of Neisseria meningitidis class 3 outer membrane protein gene variable regions and type identification using genetic techniques. Infect Immun 63:1484–1490
     [Google Scholar]
  6. Benacerraf B., Sebestyen M. M., Schlossman S. 1959; A quantitative study of the kinetics of blood clearance of P32-labelled Escherichia coli and staphylococci by the reticuloendothelial system. J Exp Med 110:27–48
     [Google Scholar]
  7. Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A.-K., Nøkleby H., Rosenqvist E., Solberg L. K., Closs O., Eng J., Frøholm L. O., Lystad A., Bakketeig L. S., Hareide B. 1991; Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338:1093–1096
     [Google Scholar]
  8. Black J. R., Black W. J., Cannon J. G. 1985; Neisserial antigen II.8 is immunogenic in patients with disseminated gonococcal and meningococcal infections. J Inject Dis 151:650–657
     [Google Scholar]
  9. Blake M. S., Gotschlich E. C. 1986; Functional and immunological properties of pathogenic neisserial surface proteins. In Bacterial Outer Membranes as Model Systems pp. 377–400 Inouye M. Edited by New York: John Wiley.;
     [Google Scholar]
  10. Brandtzaeg P., Kierulf P., Gaustad P., Skulberg A., Bruun J. N., Halvorsen S., Sørensen E. 1989; Plasma endotoxin as predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 159:195–204
     [Google Scholar]
  11. Brooks G. F., Lammel C. J., Blake M. S., Kusecek B., Achtman M. 1992; Antibodies against IgAl protease are stimulated both by clinical disease and by asymptomatic carriage of serogroup A Neisseria meningitidis . J Infect Dis 166:1316–1321
     [Google Scholar]
  12. Caugant D. A., Frøholm L. O., Selander R. K., Bøvre K. 1989; Sulfonamide resistance in Neisseria meningitidis isolates of clones of the ET-5 complex. APMIS 97:425–428
     [Google Scholar]
  13. Caugant D. A., Høiby E. A., Magnus P., Scheel O., Hoel T., Bjune G., Wedege E., Eng J, Frøholm L. O. 1994; Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J Clin Microbiol 32:323–330
     [Google Scholar]
  14. de Cossio M. E. F., Ohlin M., Llano M., Selander B., Cruz S., del Valle J., Borrebaeck C. A. K. 1992; Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis . J Infect Dis 166:1322–1328
     [Google Scholar]
  15. Delvig A., Jahn 5., Kusecek B., Heckels J. E., Rosenqvist E., Høiby E. A., Michaelsen T. E., Achtman M. 1994; A comparison of human and murine monoclonal IgGs specific for the P1.7 PorA protein of Neisseria meningitidis . Mol Immunol 31:1257–1267
     [Google Scholar]
  16. Delvig A. A., Wedege E., Caugant D. A., Dalseg R., Kolberg J., Achtman M., Rosenqvist E. 1995; A linear B-cell epitope on the class 3 outer-membrane protein of Neisseria meningitidis recognized after vaccination with the Norwegian group B outer-membrane vesicle vaccine. Microbiology 141:1593–1600
     [Google Scholar]
  17. Elkins C., Carbonetti N. H., Varela V. A., Stirewalt D., Klapper D. G., Sparling P. F. 1992; Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated. Mol Microbiol 6:2617–2628
     [Google Scholar]
  18. Feavers I. M., Suker J., McKenna A. J., Heath A. B., Maiden M. C. J. 1992; Molecular analysis of the serotyping antigens of Neisseria meningitidis . Infect Immun 60:3620–3629
     [Google Scholar]
  19. Figueroa J. E., Densen P. 1991; Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4:359–395
     [Google Scholar]
  20. Garred P., Michaelsen T. E., Bjune G., Thiel S., Svejgaard A. 1993; A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease. Scand J Immunol 37:468–470
     [Google Scholar]
  21. Geysen H. M., Meloen R. H., Barteling S. J. 1984; Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci USA 813998–4002
     [Google Scholar]
  22. Gotschlich E. C., Seiff M. E., Blake M. S., Koomey M. 1987; Porin protein of Neisseria gonorrhoeae: cloning and gene structure. Proc Natl Acad Sci USA 848135–8139
     [Google Scholar]
  23. Griffiss J. M. 1982; Epidemic meningococcal disease: synthesis of a hypothetical immunoepidemiologic model. Rev Infect Dis 4:159–172
     [Google Scholar]
  24. Guttormsen H.-K., Wetzler L. M., Næss A. 1993; Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease. Infect Immun 61:4734–4742
     [Google Scholar]
  25. Guttormsen H.-K., Wetzler L. M., Solberg C. O. 1994a; Serum opsonins induced during the course of meningococcal disease correlate with anti-outer membrane protein antibodies. In Proceedings of the Ninth Pathogenic Neisseria Conference pp. 54–55 Evans J. S., Yost S. E., Maiden M. C. J., Feavers I. M. Edited by Winchester, UK.:
     [Google Scholar]
  26. Guttormsen H.-K., Wetzler L. M., Solberg C. O. 1994b; Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease. Infect Immun 621437–1443
     [Google Scholar]
  27. Hitchcock P. J. 1989; Unified nomenclature for pathogenic Neisseria species. Clin Microbiol Rev (Supplement) 2:S64–S65
     [Google Scholar]
  28. Høiby E. A., Bjune G., Frøholm L. O., Eng J., Halstensen A., Rosenqvist E., Rønnild E., Wedege E. 1991; The Norwegian meningococcal serogroup B outer membrane vesicle protection trials: case tracing, meningococcal antigen detection and serological diagnosis. NIPH Ann 14:107–123
     [Google Scholar]
  29. Kabat E. A., Liao J., Osserman E. F., Gamian A., Michon F., Jennings H. J. 1988; The epitope associated with the binding of the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1 to a human monoclonal macroglobulin, IgMNOV. J Exp Med 168:699–711
     [Google Scholar]
  30. 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]
  31. Livingston P. O., Calves M. J., Helling F., Zollinger W. D., Blake M. S., Lowell G. H. 1993; GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3. Vaccine 11:1199–1204
     [Google Scholar]
  32. Lowell G. H., Ballou W. R., Smith L. F., Wirtz R. A., Zollinger W. D. 1988; Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides. Science 240:800–802
     [Google Scholar]
  33. Mæland J. A., Wedege E. 1989; Serum antibodies to crossreactive Neisseria outer membrane antigens in healthy persons and patients with meningococcal disease. APMIS 97:774–780
     [Google Scholar]
  34. Mandrell R. E., Zollinger W. D. 1989; Human immune response to meningococcal outer membrane protein epitopes after natural infection or vaccination. Infect Immun 57:1590–1598
     [Google Scholar]
  35. Mee B. J., Thomas H., Cooke S. J., Lambden P. R., Heckels J. E. 1993; Structural comparison and epitope analysis of outer- membrane protein PIA from strains of Neisseria gonorrhoeae with different serovat specificities. J Gen Microbiol 139:2613–2620
     [Google Scholar]
  36. Melancon Kaplan J., Murgita R. A. 1987; Modulation of the immune system by Neisseria meningitidis . Scand J Immunol 26:213–221
     [Google Scholar]
  37. Meola A., Delmastro P., Monaci P., Luzzago A., Nicosia A., Felici F., Cortese R., Galfre G. 1995; Derivation of vaccines from mimotopes. Immunologic properties of human Hepatitis B virus surface antigen mimotopes displayed on filamentous phage. J Immunol 154:3162–3172
     [Google Scholar]
  38. Moran E. E., Brandt B. L., Zollinger W. D. 1994; Expression of the L8 lipopolysaccharide determinant increases the sensitivity of Neisseria meningitidis to serum bactericidal activity. Infect Immun 62:5290–5295
     [Google Scholar]
  39. Morelli G., del Valle J., Lammel C. J., Pohlner J., Müller K., Blake M., Brooks G. F., Meyer T. F., Koumaré B., Brieske N., Achtman M. 1994; Immunogenicity and evolutionary variability of epitopes within IgAl protease from serogroup A Neisseria meningitidis . Mot Microbiol 11:175–187
     [Google Scholar]
  40. Orren A., Warren R. E., Potter P. C., Jones A. M., Lachmann P. J., Poolman J. T. 1992; Antibodies to meningococcal class 1 outer membrane proteins in South African complement-deficient and complement-sufficient subjects. Infect Immun 60:4510–4516
     [Google Scholar]
  41. Poolman J. T., Hopman C. T. P., Zanen H. C. 1983; Immunogenicity of meningococcal antigens as detected in patient sera. Infect Immun 40:398–406
     [Google Scholar]
  42. Raziuddin S., El-Awad M. E., Mir N. A. 1991; Bacterial meningitis: T cell activation and immunoregulatory CD4+ T cell subset alteration. J Allergy Clin Immunol 87:1115–1120
     [Google Scholar]
  43. Raziuddin S., Mir N. A., El-Awad M. E., Telmesani A. W., Al-Janadi M. 1994; γ/δ-T lymphocytes and proinflamatory cytokines in bacterial meningitis. J Allergy Clin Immunol 93:793–789
     [Google Scholar]
  44. Romero J. D., Outschoorn I. M. 1994; Current status of meningococcal group B vaccine candidates: capsular or noncapsular?. Clin Microbiol Rev 7:559–575
     [Google Scholar]
  45. Rosenqvist E, Høiby E. A., Wedege E., Kusecek B., Achtman M. 1993; The 5C protein of Neisseria meningitidis is highly immunogenic in humans and stimulates bactericidal antibodies. J Infect Dis 167:1065–1073
     [Google Scholar]
  46. Ross S. C., Rosenthal P. J., Berberich H. M., Densen P. 1987; Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals. J Infect Dis 155:1266–1275
     [Google Scholar]
  47. Rothbard J. B., Fernandez R., Schoolnik G. K. 1984; Strain specific and common epitopes of gonococcal pili. J Exp Med 160:208–221
     [Google Scholar]
  48. 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 Pathog 3:261–267
     [Google Scholar]
  49. Siber G. R. 1994; Pneumococcal disease: prospects for a new generation of vaccines. Science 265:1385–1387
     [Google Scholar]
  50. Van Regenmortel M. H. V. 1992; Molecular dissection of protein antigens. In Structure of Antigens 1 pp. 1–27 Van Regenmortel M. H. V. Edited by London: CRC Press.;
     [Google Scholar]
  51. Ward M. J., Lambden P. R., Heckels J. E. 1992; Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species. FEMS Microbiol Lett 73:283–289
     [Google Scholar]
  52. Wedege E., Bryn K., Frøholm L. O. 1988; Restoration of antibody binding to blotted meningococcal outer membrane proteins using various detergents. J Immunol Methods 113:51–59
     [Google Scholar]
  53. Wedege E., Bjune G., Frøholm L.0., Høiby E. A., Rosenqvist E. 1991; Immunoblotting studies of vaccinee and patient sera from the Norwegian serogroup B meningococcal vaccination trial. NIPH Ann 14:183–187
     [Google Scholar]
  54. Wetzler L. M., Blake M. S., Gotschlich E. C. 1988; Characterization and specificity of antibodies to protein I of Neisseria gonorrhoeae produced by injection with various protein I-adjuvant preparations. J Exp Med 168:1883–1897
     [Google Scholar]
  55. Wiertz E.J.H.J., Van Gaans-van den Brink J. A. M., Schreuder G.M.T.H., Termijtelen A. A. M., Hoogerhout P., Poolman J. T. 1991; T cell recognition of Neisseria meningitidis class I outer membrane proteins: identification of T cell epitopes with selected synthetic peptides and determination of HLA restriction elements. J Immunol 147:2012–2018
     [Google Scholar]
  56. Wiertz E.J.H.J., Van Gaans-van den Brink J. A. M., Gausepohl H., Prochnicka-Chalufour A., Hoogerhout P., Poolman J. T. 1992; Identification of T cell epitopes occurring in a meningococcal class 1 outer membrane protein using overlapping peptides assembled with simultaneous multiple peptide synthesis. J Exp Med 176:79–86
     [Google Scholar]
  57. Wolff K., Stem A. 1991; The class 3 outer membrane protein (PorB) of Neisseria meningitidis: gene sequence and homology to the gonococcal porin PIA. FEMS Microbiol Lett 83:179–186
     [Google Scholar]
  58. Zapata G. A., Vann W. F., Rubinstein Y., Frasch C. E. 1992; Identification of variable region differences in Neisseria meningitidis class 3 protein sequences among five group B serotypes. Mol Microbiol 6:3493–3499
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-142-9-2491
Loading
Immune responses to linear epitopes on the PorB protein of Neisseria meningitidis in patients with systemic meningococcal disease
Microbiology 142, 2491 (1996); https://doi.org/10.1099/00221287-142-9-2491
/content/journal/micro/10.1099/00221287-142-9-2491
/content/journal/micro/10.1099/00221287-142-9-2491
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error