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Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1995 May;2(3):314–321. doi: 10.1128/cdli.2.3.314-321.1995

Emergence of a new virulent clone within the electrophoretic type 5 complex of serogroup B meningococci in Norway.

E Wedege 1, J Kolberg 1, A Delvig 1, E A Høiby 1, E Holten 1, E Rosenqvist 1, D A Caugant 1
PMCID: PMC170152  PMID: 7664178

Abstract

An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains. Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates. The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world. All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway. A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction. Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively. Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a. Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c. Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone.

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Selected References

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  1. Achtman M. Clonal spread of serogroup A meningococci: a paradigm for the analysis of microevolution in bacteria. Mol Microbiol. 1994 Jan;11(1):15–22. doi: 10.1111/j.1365-2958.1994.tb00285.x. [DOI] [PubMed] [Google Scholar]
  2. Ashton F. E., Mancino L., Ryan A. J., Poolman J. T., Abdillahi H., Zollinger W. D. Serotypes and subtypes of Neisseria meningitidis serogroup B strains associated with meningococcal disease in Canada, 1977-1989. Can J Microbiol. 1991 Aug;37(8):613–617. doi: 10.1139/m91-104. [DOI] [PubMed] [Google Scholar]
  3. Barlow A. K., Heckels J. E., Clarke I. N. The class 1 outer membrane protein of Neisseria meningitidis: gene sequence and structural and immunological similarities to gonococcal porins. Mol Microbiol. 1989 Feb;3(2):131–139. doi: 10.1111/j.1365-2958.1989.tb01802.x. [DOI] [PubMed] [Google Scholar]
  4. Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H., Rosenqvist E. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet. 1991 Nov 2;338(8775):1093–1096. doi: 10.1016/0140-6736(91)91961-s. [DOI] [PubMed] [Google Scholar]
  5. Caugant D. A., Bol P., Høiby E. A., Zanen H. C., Frøholm L. O. Clones of serogroup B Neisseria meningitidis causing systemic disease in The Netherlands, 1958-1986. J Infect Dis. 1990 Oct;162(4):867–874. doi: 10.1093/infdis/162.4.867. [DOI] [PubMed] [Google Scholar]
  6. Caugant D. A., Frøholm L. O., Bøvre K., Holten E., Frasch C. E., Mocca L. F., Zollinger W. D., Selander R. K. Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4927–4931. doi: 10.1073/pnas.83.13.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caugant D. A., Høiby E. A., Magnus P., Scheel O., Hoel T., Bjune G., Wedege E., Eng J., Frøholm L. O. Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J Clin Microbiol. 1994 Feb;32(2):323–330. doi: 10.1128/jcm.32.2.323-330.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feavers I. M., Heath A. B., Bygraves J. A., Maiden M. C. Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis. Mol Microbiol. 1992 Feb;6(4):489–495. doi: 10.1111/j.1365-2958.1992.tb01493.x. [DOI] [PubMed] [Google Scholar]
  9. Frasch C. E., Zollinger W. D., Poolman J. T. Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes. Rev Infect Dis. 1985 Jul-Aug;7(4):504–510. doi: 10.1093/clinids/7.4.504. [DOI] [PubMed] [Google Scholar]
  10. Garred P., Michaelsen T. E., Bjune G., Thiel S., Svejgaard A. A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease. Scand J Immunol. 1993 Apr;37(4):468–470. doi: 10.1111/j.1365-3083.1993.tb03320.x. [DOI] [PubMed] [Google Scholar]
  11. Geysen H. M., Rodda S. J., Mason T. J., Tribbick G., Schoofs P. G. Strategies for epitope analysis using peptide synthesis. J Immunol Methods. 1987 Sep 24;102(2):259–274. doi: 10.1016/0022-1759(87)90085-8. [DOI] [PubMed] [Google Scholar]
  12. Gilja O. H., Halstensen A., Digranes A., Mylvaganam H., Aksnes A., Høiby E. A. Use of single-dose ofloxacin to eradicate tonsillopharyngeal carriage of Neisseria meningitidis. Antimicrob Agents Chemother. 1993 Sep;37(9):2024–2026. doi: 10.1128/aac.37.9.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guttormsen H. K., Wetzler L. M., Solberg C. O. Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease. Infect Immun. 1994 Apr;62(4):1437–1443. doi: 10.1128/iai.62.4.1437-1443.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hitchcock P. J. Unified nomenclature for pathogenic Neisseria species. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S64–S65. doi: 10.1128/cmr.2.suppl.s64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Høiby E. A., Bjune G., Frøholm L. O., Eng J., Halstensen A., Rosenqvist E., Rønnild E., Wedege E. The Norwegian meningococcal serogroup B outer membrane vesicle vaccine protection trials: case tracing, meningococcal antigen detection and serological diagnosis. NIPH Ann. 1991 Dec;14(2):107–123. [PubMed] [Google Scholar]
  16. Høiby E. A., Rosenqvist E., Frøholm L. O., Bjune G., Feiring B., Nøkleby H., Rønnild E. Bactericidal antibodies after vaccination with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine: a brief survey. NIPH Ann. 1991 Dec;14(2):147–156. [PubMed] [Google Scholar]
  17. Laver W. G., Air G. M., Webster R. G., Smith-Gill S. J. Epitopes on protein antigens: misconceptions and realities. Cell. 1990 May 18;61(4):553–556. doi: 10.1016/0092-8674(90)90464-p. [DOI] [PubMed] [Google Scholar]
  18. Maiden M. C., Bygraves J. A., McCarvil J., Feavers I. M. Identification of meningococcal serosubtypes by polymerase chain reaction. J Clin Microbiol. 1992 Nov;30(11):2835–2841. doi: 10.1128/jcm.30.11.2835-2841.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maiden M. C. Population genetics of a transformable bacterium: the influence of horizontal genetic exchange on the biology of Neisseria meningitidis. FEMS Microbiol Lett. 1993 Sep 15;112(3):243–250. doi: 10.1111/j.1574-6968.1993.tb06457.x. [DOI] [PubMed] [Google Scholar]
  20. Maiden M. C., Suker J., McKenna A. J., Bygraves J. A., Feavers I. M. Comparison of the class 1 outer membrane proteins of eight serological reference strains of Neisseria meningitidis. Mol Microbiol. 1991 Mar;5(3):727–736. doi: 10.1111/j.1365-2958.1991.tb00743.x. [DOI] [PubMed] [Google Scholar]
  21. Mandrell R. E., Zollinger W. D. Human immune response to meningococcal outer membrane protein epitopes after natural infection or vaccination. Infect Immun. 1989 May;57(5):1590–1598. doi: 10.1128/iai.57.5.1590-1598.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mandrell R. E., Zollinger W. D. Use of a zwitterionic detergent for the restoration of the antibody-binding capacity of electroblotted meningococcal outer membrane proteins. J Immunol Methods. 1984 Feb 24;67(1):1–11. doi: 10.1016/0022-1759(84)90080-2. [DOI] [PubMed] [Google Scholar]
  23. McCarvil J., McKenna A. J., Grief C., Hoy C. S., Sesardic D., Maiden M. C., Feavers I. M. Expression of meningococcal epitopes in LamB of Escherichia coli and the stimulation of serosubtype-specific antibody responses. Mol Microbiol. 1993 Oct;10(1):203–213. doi: 10.1111/j.1365-2958.1993.tb00916.x. [DOI] [PubMed] [Google Scholar]
  24. McGuinness B. T., Clarke I. N., Lambden P. R., Barlow A. K., Poolman J. T., Jones D. M., Heckels J. E. Point mutation in meningococcal por A gene associated with increased endemic disease. Lancet. 1991 Mar 2;337(8740):514–517. doi: 10.1016/0140-6736(91)91297-8. [DOI] [PubMed] [Google Scholar]
  25. McGuinness B. T., Lambden P. R., Heckels J. E. 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. 1993 Feb;7(4):505–514. doi: 10.1111/j.1365-2958.1993.tb01141.x. [DOI] [PubMed] [Google Scholar]
  26. McGuinness B., Barlow A. K., Clarke I. N., Farley J. E., Anilionis A., Poolman J. T., Heckels J. E. 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. 1990 Jun 1;171(6):1871–1882. doi: 10.1084/jem.171.6.1871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mocca L. F., Frasch C. E. Sodium dodecyl sulfate-polyacrylamide gel typing system for characterization of Neisseria meningitidis isolates. J Clin Microbiol. 1982 Aug;16(2):240–244. doi: 10.1128/jcm.16.2.240-244.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosenqvist E., Høiby E. A., Wedege E., Caugant D. A., Frøholm L. O., McGuinness B. T., Brooks J., Lambden P. R., Heckels J. E. A new variant of serosubtype P1.16 in Neisseria meningitidis from Norway, associated with increased resistance to bactericidal antibodies induced by a serogroup B outer membrane protein vaccine. Microb Pathog. 1993 Sep;15(3):197–205. doi: 10.1006/mpat.1993.1070. [DOI] [PubMed] [Google Scholar]
  29. Rosenqvist E., Høiby E. A., Wedege E., Kusecek B., Achtman M. The 5C protein of Neisseria meningitidis is highly immunogenic in humans and induces bactericidal antibodies. J Infect Dis. 1993 May;167(5):1065–1073. doi: 10.1093/infdis/167.5.1065. [DOI] [PubMed] [Google Scholar]
  30. Saukkonen K., Leinonen M., Abdillahi H., Poolman J. T. Comparative evaluation of potential components for group B meningococcal vaccine by passive protection in the infant rat and in vitro bactericidal assay. Vaccine. 1989 Aug;7(4):325–328. doi: 10.1016/0264-410x(89)90194-1. [DOI] [PubMed] [Google Scholar]
  31. Scholten R. J., Bijlmer H. A., Poolman J. T., Kuipers B., Caugant D. A., Van Alphen L., Dankert J., Valkenburg H. A. Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis. Clin Infect Dis. 1993 Feb;16(2):237–246. doi: 10.1093/clind/16.2.237. [DOI] [PubMed] [Google Scholar]
  32. Smith J. M., Dowson C. G., Spratt B. G. Localized sex in bacteria. Nature. 1991 Jan 3;349(6304):29–31. doi: 10.1038/349029a0. [DOI] [PubMed] [Google Scholar]
  33. Suker J., Feavers I. M., Achtman M., Morelli G., Wang J. F., Maiden M. C. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation. Mol Microbiol. 1994 Apr;12(2):253–265. doi: 10.1111/j.1365-2958.1994.tb01014.x. [DOI] [PubMed] [Google Scholar]
  34. Tommassen J., Vermeij P., Struyvé M., Benz R., Poolman J. T. Isolation of Neisseria meningitidis mutants deficient in class 1 (porA) and class 3 (porB) outer membrane proteins. Infect Immun. 1990 May;58(5):1355–1359. doi: 10.1128/iai.58.5.1355-1359.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Van Der Ley P., Poolman J. T. Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. Infect Immun. 1992 Aug;60(8):3156–3161. doi: 10.1128/iai.60.8.3156-3161.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Virji M., Heckels J. E. Location of a blocking epitope on outer-membrane protein III of Neisseria gonorrhoeae by synthetic peptide analysis. J Gen Microbiol. 1989 Jul;135(7):1895–1899. doi: 10.1099/00221287-135-7-1895. [DOI] [PubMed] [Google Scholar]
  37. Wedege E., Bjune G., Frøholm L. O., Høiby E. A., Rosenqvist E. Immunoblotting studies of vaccinee and patient sera from a Norwegian serogroup B meningococcal vaccination trial. NIPH Ann. 1991 Dec;14(2):183–186. [PubMed] [Google Scholar]
  38. Wedege E., Bryn K., Frøholm L. O. Restoration of antibody binding to blotted meningococcal outer membrane proteins using various detergents. J Immunol Methods. 1988 Oct 4;113(1):51–59. doi: 10.1016/0022-1759(88)90381-x. [DOI] [PubMed] [Google Scholar]
  39. Wedege E., Dalseg R., Caugant D. A., Poolman J. T., Frøholm L. O. Expression of an inaccessible P1.7 subtype epitope on meningococcal class 1 proteins. J Med Microbiol. 1993 Jan;38(1):23–28. doi: 10.1099/00222615-38-1-23. [DOI] [PubMed] [Google Scholar]
  40. Wedege E., Frøholm L. O. Human antibody response to a group B serotype 2a meningococcal vaccine determined by immunoblotting. Infect Immun. 1986 Feb;51(2):571–578. doi: 10.1128/iai.51.2.571-578.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wedege E., Høiby E. A., Rosenqvist E., Frøholm L. O. Serotyping and subtyping of Neisseria meningitidis isolates by co-agglutination, dot-blotting and ELISA. J Med Microbiol. 1990 Mar;31(3):195–201. doi: 10.1099/00222615-31-3-195. [DOI] [PubMed] [Google Scholar]
  42. van der Ley P., Heckels J. E., Virji M., Hoogerhout P., Poolman J. T. Topology of outer membrane porins in pathogenic Neisseria spp. Infect Immun. 1991 Sep;59(9):2963–2971. doi: 10.1128/iai.59.9.2963-2971.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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