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. 1995 Sep;63(9):3531–3536. doi: 10.1128/iai.63.9.3531-3536.1995

Comparison among opsonic activity, antimeningococcal immunoglobulin G response, and serum bactericidal activity against meningococci in sera from vaccinees after immunization with a serogroup B outer membrane vesicle vaccine.

A Aase 1, G Bjune 1, E A Høiby 1, E Rosenqvist 1, A K Pedersen 1, T E Michaelsen 1
PMCID: PMC173489  PMID: 7642288

Abstract

Opsonic activity in sera from 27 military recruits vaccinated with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine was measured as respiratory burst with polymorphonuclear leukocytes as the effector cells and meningococci of the epidemic strain as the target. The results were compared with antimeningococcal IgG antibodies against an outer membrane vesicle coat in an enzyme-linked immunosorbent assay and with serum bactericidal activity. The vaccinees were immunized twice, with a 6-week interval between the two. The serum samples studied were collected at day zero, after 6 weeks, and after 12 weeks. Both serum bactericidal activity and respiratory burst were measured by adding external serum as the complement source. The results revealed a significant increase in specific IgG response, serum bactericidal activity, and respiratory burst after vaccination. We found a highly significant correlation between the responses in all three assays (P < 0.0001). The highest correlation was found between respiratory burst and antimeningococcal IgG response (r = 0.93). This result strongly indicates that respiratory burst is mediated almost exclusively by IgG antibodies. The correlation between antimeningococcal IgG response and serum bactericidal activity was slightly lower (r = 0.83). The correlation between respiratory burst and serum bactericidal activity was further reduced (r = 0.78), and some of the sera revealed a marked preference for only one of the activities. This result means that respiratory burst and serum bactericidal activity in part are induced by different mediators, and to obtain a more complete picture of the potential protective activity, both assays should be applied to survey a vaccine trial.

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Selected References

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  1. Aase A., Michaelsen T. E. Opsonophagocytic activity induced by chimeric antibodies of the four human IgG subclasses with or without help from complement. Scand J Immunol. 1994 Jun;39(6):581–587. doi: 10.1111/j.1365-3083.1994.tb03416.x. [DOI] [PubMed] [Google Scholar]
  2. Bjune G., Closs O., Frøholm L. O., Grønnesby J. K., Høiby E. A., Nøkleby H. Design of clinical trials with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway. NIPH Ann. 1991 Dec;14(2):81–93. [PubMed] [Google Scholar]
  3. 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]
  4. Brandtzaeg P., Mollnes T. E., Kierulf P. Complement activation and endotoxin levels in systemic meningococcal disease. J Infect Dis. 1989 Jul;160(1):58–65. doi: 10.1093/infdis/160.1.58. [DOI] [PubMed] [Google Scholar]
  5. Bredius R. G., de Vries C. E., Troelstra A., van Alphen L., Weening R. S., van de Winkel J. G., Out T. A. Phagocytosis of Staphylococcus aureus and Haemophilus influenzae type B opsonized with polyclonal human IgG1 and IgG2 antibodies. Functional hFc gamma RIIa polymorphism to IgG2. J Immunol. 1993 Aug 1;151(3):1463–1472. [PubMed] [Google Scholar]
  6. Caugant D. A., Høiby E. A., Rosenqvist E., Frøholm L. O., Selander R. K. Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol Infect. 1992 Oct;109(2):241–253. doi: 10.1017/s0950268800050196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Delvig A., Jahn S., Kusecek B., Heckels J. E., Rosenqvist E., Høiby E. A., Michaelsen T. E., Achtman M. A comparison of human and murine monoclonal IgGs specific for the P1.7 PorA protein of Neisseria meningitidis. Mol Immunol. 1994 Nov;31(16):1257–1267. doi: 10.1016/0161-5890(94)90076-0. [DOI] [PubMed] [Google Scholar]
  8. Figueroa J. E., Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. 1991 Jul;4(3):359–395. doi: 10.1128/cmr.4.3.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frasch C. E., Robbins J. D. Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model. J Exp Med. 1978 Mar 1;147(3):629–644. doi: 10.1084/jem.147.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fredlund H. Serum factors and polymorphonuclear leukocytes in human host defence against Neisseria meningitidis. Studies of interactions with special reference to a chemiluminometric technique. Scand J Infect Dis Suppl. 1993;87:1–72. [PubMed] [Google Scholar]
  11. Fredriksen J. H., Rosenqvist E., Wedege E., Bryn K., Bjune G., Frøholm L. O., Lindbak A. K., Møgster B., Namork E., Rye U. Production, characterization and control of MenB-vaccine "Folkehelsa": an outer membrane vesicle vaccine against group B meningococcal disease. NIPH Ann. 1991 Dec;14(2):67–80. [PubMed] [Google Scholar]
  12. Garred P., Michaelsen T. E., Aase A. The IgG subclass pattern of complement activation depends on epitope density and antibody and complement concentration. Scand J Immunol. 1989 Sep;30(3):379–382. doi: 10.1111/j.1365-3083.1989.tb01225.x. [DOI] [PubMed] [Google Scholar]
  13. Goldschneider I., Gotschlich E. C., Artenstein M. S. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969 Jun 1;129(6):1307–1326. doi: 10.1084/jem.129.6.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Halstensen A., Haneberg B., Frøholm L. O., Lehmann V., Frasch C. E., Solberg C. O. Human opsonins to meningococci after vaccination. Infect Immun. 1984 Dec;46(3):673–676. doi: 10.1128/iai.46.3.673-676.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Halstensen A., Haneberg B., Glette J., Sandberg S., Solberg C. O. Factors important for the measurement of chemiluminescence production by polymorphonuclear leukocytes. J Immunol Methods. 1986 Apr 3;88(1):121–128. doi: 10.1016/0022-1759(86)90060-8. [DOI] [PubMed] [Google Scholar]
  16. Halstensen A., Haneberg B. Standardization of a chemiluminescence method for the measurement of meningococcal opsonins using ethanol fixed meningococci. Acta Pathol Microbiol Immunol Scand C. 1987 Aug;95(4):155–160. doi: 10.1111/j.1699-0463.1987.tb00024.x. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Jarvis G. A., Griffiss J. M. Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule. J Immunol. 1991 Sep 15;147(6):1962–1967. [PubMed] [Google Scholar]
  20. Lehner P. J., Davies K. A., Walport M. J., Cope A. P., Würzner R., Orren A., Morgan B. P., Cohen J. Meningococcal septicaemia in a C6-deficient patient and effects of plasma transfusion on lipopolysaccharide release. Lancet. 1992 Dec 5;340(8832):1379–1381. doi: 10.1016/0140-6736(92)92561-s. [DOI] [PubMed] [Google Scholar]
  21. Lowell G. H., Smith L. F., Griffiss J. M., Brandt B. L., MacDermott R. P. Antibody-dependent mononuclear cell-mediated antimeningococcal activity. Comparison of the effects of convalescent and postimmunization immunoglobulins G, M, and A. J Clin Invest. 1980 Aug;66(2):260–267. doi: 10.1172/JCI109852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lystad A., Aasen S. The epidemiology of meningococcal disease in Norway 1975-91. NIPH Ann. 1991 Dec;14(2):57–66. [PubMed] [Google Scholar]
  23. Michaelsen T. E., Garred P., Aase A. Human IgG subclass pattern of inducing complement-mediated cytolysis depends on antigen concentration and to a lesser extent on epitope patchiness, antibody affinity and complement concentration. Eur J Immunol. 1991 Jan;21(1):11–16. doi: 10.1002/eji.1830210103. [DOI] [PubMed] [Google Scholar]
  24. Munkley A., Tinsley C. R., Virji M., Heckels J. E. Blocking of bactericidal killing of Neisseria meningitidis by antibodies directed against class 4 outer membrane protein. Microb Pathog. 1991 Dec;11(6):447–452. doi: 10.1016/0882-4010(91)90041-8. [DOI] [PubMed] [Google Scholar]
  25. Parren P. W., Warmerdam P. A., Boeije L. C., Arts J., Westerdaal N. A., Vlug A., Capel P. J., Aarden L. A., van de Winkel J. G. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. J Clin Invest. 1992 Oct;90(4):1537–1546. doi: 10.1172/JCI116022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Raff H. V., Devereux D., Shuford W., Abbott-Brown D., Maloney G. Human monoclonal antibody with protective activity for Escherichia coli K1 and Neisseria meningitidis group B infections. J Infect Dis. 1988 Jan;157(1):118–126. doi: 10.1093/infdis/157.1.118. [DOI] [PubMed] [Google Scholar]
  27. Rosenqvist E., Harthug S., Frøholm L. O., Høiby E. A., Bøvre K., Zollinger W. D. Antibody responses to serogroup B meningococcal outer membrane antigens after vaccination and infection. J Clin Microbiol. 1988 Aug;26(8):1543–1548. doi: 10.1128/jcm.26.8.1543-1548.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosenqvist E., Høiby E. A., Bjune G., Bryn K., Closs O., Feiring B., Klem A., Nøkleby H., Frølm L. O. Human antibody responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine: results from ELISA studies. NIPH Ann. 1991 Dec;14(2):169–181. [PubMed] [Google Scholar]
  29. Ross G. D. Complement and complement receptors. Curr Opin Immunol. 1989 Oct;2(1):50–62. doi: 10.1016/0952-7915(89)90097-6. [DOI] [PubMed] [Google Scholar]
  30. Ross S. C., Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984 Sep;63(5):243–273. [PubMed] [Google Scholar]
  31. Ross S. C., Rosenthal P. J., Berberich H. M., Densen P. Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals. J Infect Dis. 1987 Jun;155(6):1266–1275. doi: 10.1093/infdis/155.6.1266. [DOI] [PubMed] [Google Scholar]
  32. Rothe G., Oser A., Valet G. Dihydrorhodamine 123: a new flow cytometric indicator for respiratory burst activity in neutrophil granulocytes. Naturwissenschaften. 1988 Jul;75(7):354–355. doi: 10.1007/BF00368326. [DOI] [PubMed] [Google Scholar]
  33. Sjursen H., Bjerknes R., Halstensen A., Naess A., Frøholm L. O., Rosenqvist E., Solberg C. O. Serum opsonins to group B meningococci. Acta Pathol Microbiol Immunol Scand C. 1987 Dec;95(6):283–289. doi: 10.1111/j.1699-0463.1987.tb00042.x. [DOI] [PubMed] [Google Scholar]
  34. Sjursen H., Bjerknes R., Halstensen A., Naess A., Sørnes S., Solberg C. O. Flow cytometric assay for the measurement of serum opsonins to Neisseria meningitidis serogroup B, serotype 15. J Immunol Methods. 1989 Jan 17;116(2):235–243. doi: 10.1016/0022-1759(89)90209-3. [DOI] [PubMed] [Google Scholar]
  35. Sjursen H., Lehmann V., Naess A., Hervig T., Flø R. W., Maehle B., Halstensen A. I., Frøholm L. O. Monocyte phagocytosis of opsonized Neisseria meningitidis serogroup B. APMIS. 1992 Mar;100(3):209–220. [PubMed] [Google Scholar]
  36. Warmerdam P. A., van de Winkel J. G., Vlug A., Westerdaal N. A., Capel P. J. A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. J Immunol. 1991 Aug 15;147(4):1338–1343. [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. van de Winkel J. G., Capel P. J. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today. 1993 May;14(5):215–221. doi: 10.1016/0167-5699(93)90166-I. [DOI] [PubMed] [Google Scholar]

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