Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1993 Nov;61(11):4734–4742. doi: 10.1128/iai.61.11.4734-4742.1993

Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease.

H K Guttormsen 1, L M Wetzler 1, A Naess 1
PMCID: PMC281228  PMID: 8406872

Abstract

We have determined the amounts of specific anti-class 3 outer membrane protein antibodies of immunoglobulin G (IgG), IgM, and IgA isotypes in patient sera during the course of meningococcal disease by using purified class 3 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay. The class 3 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 1 and class 4 outer membrane proteins. Serum samples from 25 patients with systemic meningococcal disease caused by organisms of various serotypes were collected during the course of disease. Seven of these patients had been immunized with a meningococcal outer membrane vesicle vaccine made from strain 44/76 prior to disease. An increase in specific anti-class 3 (type 15) outer membrane protein IgG antibodies was demonstrated in 22 of 25 patients (88%), regardless of the serotype of the infecting strain. This indicates that the specific anti-class 3 antibodies were reacting in part with epitopes not determined by the monoclonal antibodies used for serotyping. A considerable heterogeneity in antibody levels and IgG subclass response was seen. Most patients had low levels of anti-class 3 antibodies during the acute illness, with antibodies peaking during the second week of disease and returning to near baseline in sera collected 6 to 12 months after the onset of the disease. The majority of the specific anti-class 3 IgG antibodies were shown to bind to surface-exposed epitopes on the whole bacteria and to belong to IgG1 and IgG3. The highest anti-class 3 IgG peak levels were seen in patients infected with strains of the homologous serotype after vaccination with the meningococcal outer membrane vesicle vaccine, suggesting an anamnestic response. However, these patients were not protected from meningococcal disease after immunization.

Full text

PDF
4734

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Blake M. S., Gotschlich E. C. Purification and partial characterization of the major outer membrane protein of Neisseria gonorrhoeae. Infect Immun. 1982 Apr;36(1):277–283. doi: 10.1128/iai.36.1.277-283.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blake M. S., MacDonald C. M., Klugman K. P. Colony morphology of piliated Neisseria meningitidis. J Exp Med. 1989 Nov 1;170(5):1727–1736. doi: 10.1084/jem.170.5.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brodeur B. R., Larose Y., Tsang P., Hamel J., Ashton F., Ryan A. Protection against infection with Neisseria meningitidis group B serotype 2b by passive immunization with serotype-specific monoclonal antibody. Infect Immun. 1985 Nov;50(2):510–516. doi: 10.1128/iai.50.2.510-516.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burton D. R., Gregory L., Jefferis R. Aspects of the molecular structure of IgG subclasses. Monogr Allergy. 1986;19:7–35. [PubMed] [Google Scholar]
  6. Davies R. L., Wall R. A., Borriello S. P. Comparison of methods for the analysis of outer membrane antigens of Neisseria meningitidis by western blotting. J Immunol Methods. 1990 Dec 5;134(2):215–225. doi: 10.1016/0022-1759(90)90383-7. [DOI] [PubMed] [Google Scholar]
  7. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972 Jul;109(1):129–135. [PubMed] [Google Scholar]
  8. Guttormsen H. K., Bjerknes R., Naess A., Lehmann V., Halstensen A., Sørnes S., Solberg C. O. Cross-reacting serum opsonins in patients with meningococcal disease. Infect Immun. 1992 Jul;60(7):2777–2783. doi: 10.1128/iai.60.7.2777-2783.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hammarström L., Smith C. I. IgG subclasses in bacterial infections. Monogr Allergy. 1986;19:122–133. [PubMed] [Google Scholar]
  10. Harthug S., Rosenqvist E., Høiby E. A., Gedde-Dahl T. W., Frøholm L. O. Antibody response in group B meningococcal disease determined by enzyme-linked immunosorbent assay with serotype 15 outer membrane antigen. J Clin Microbiol. 1986 Dec;24(6):947–953. doi: 10.1128/jcm.24.6.947-953.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jones D. M., Borrow R., Fox A. J., Gray S., Cartwright K. A., Poolman J. T. The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis. Microb Pathog. 1992 Sep;13(3):219–224. doi: 10.1016/0882-4010(92)90022-g. [DOI] [PubMed] [Google Scholar]
  12. Klugman K. P., Gotschlich E. C., Blake M. S. Sequence of the structural gene (rmpM) for the class 4 outer membrane protein of Neisseria meningitidis, homology of the protein to gonococcal protein III and Escherichia coli OmpA, and construction of meningococcal strains that lack class 4 protein. Infect Immun. 1989 Jul;57(7):2066–2071. doi: 10.1128/iai.57.7.2066-2071.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Maeland J. A., Wedege E. Serum antibodies to cross-reactive Neisseria outer membrane antigens in healthy persons and patients with meningococcal disease. APMIS. 1989 Sep;97(9):774–780. doi: 10.1111/j.1699-0463.1989.tb00477.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Mandrell R. E., Zollinger W. D. Lipopolysaccharide serotyping of Neisseria meningitidis by hemagglutination inhibition. Infect Immun. 1977 May;16(2):471–475. doi: 10.1128/iai.16.2.471-475.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poolman J. T., Hopman C. T., Zanen H. C. Immunogenicity of meningococcal antigens as detected in patient sera. Infect Immun. 1983 Apr;40(1):398–406. doi: 10.1128/iai.40.1.398-406.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Sjursen H., Wedege E., Rosenqvist E., Naess A., Halstensen A., Matre R., Solberg C. O. IgG subclass antibodies to serogroup B meningococcal outer membrane antigens following infection and vaccination. APMIS. 1990 Dec;98(12):1061–1069. doi: 10.1111/j.1699-0463.1990.tb05035.x. [DOI] [PubMed] [Google Scholar]
  20. Swanson J. Studies on gonococcus infection. XII. Colony color and opacity varienats of gonococci. Infect Immun. 1978 Jan;19(1):320–331. doi: 10.1128/iai.19.1.320-331.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Tsai C. M. The analysis of lipopolysaccharide (endotoxin) in meningococcal polysaccharide vaccines by silver staining following SDS-polyacrylamide gel electrophoresis. J Biol Stand. 1986 Jan;14(1):25–33. doi: 10.1016/s0092-1157(86)80006-3. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Wedege E., Michaelsen T. E. Human immunoglobulin G subclass immune response to outer membrane antigens in meningococcal group B vaccine. J Clin Microbiol. 1987 Aug;25(8):1349–1353. doi: 10.1128/jcm.25.8.1349-1353.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wetzler L. M., Blake M. S., Barry K., Gotschlich E. C. Gonococcal porin vaccine evaluation: comparison of Por proteosomes, liposomes, and blebs isolated from rmp deletion mutants. J Infect Dis. 1992 Sep;166(3):551–555. doi: 10.1093/infdis/166.3.551. [DOI] [PubMed] [Google Scholar]
  26. Wetzler L. M., Blake M. S., Gotschlich E. C. Characterization and specificity of antibodies to protein I of Neisseria gonorrhoeae produced by injection with various protein I-adjuvant preparations. J Exp Med. 1988 Nov 1;168(5):1883–1897. doi: 10.1084/jem.168.5.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wyle F. A., Artenstein M. S., Brandt B. L., Tramont E. C., Kasper D. L., Altieri P. L., Berman S. L., Lowenthal J. P. Immunologic response of man to group B meningococcal polysaccharide vaccines. J Infect Dis. 1972 Nov;126(5):514–521. doi: 10.1093/infdis/126.5.514. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES