Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 May;63(5):836–848. doi: 10.1172/JCI109383

Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

W D Zollinger 1, R E Mandrell 1, J M Griffiss 1, P Altieri 1, S Berman 1
PMCID: PMC372024  PMID: 109466

Abstract

A noncovalent complex of meningococcal group B polysaccharide and type 2 outer membrane protein has been characterized and its potential as a vaccine against group B meningococcal disease investigated. The polysaccharide component was found to have a partition coefficient, Kd, of 0.34 on Sepharose CL-4B in the presence of sodium deoxycholate. The protein consisted of four to five major proteins including the principal outer membrane protein. Hydrophobic binding between the protein and polysaccharide was demonstrated by gel filtration and isopycnic CsCl density gradient centrifugation and found to involve all of the proteins. After demonstrating safety and immunogenicity in animals, two lots of vaccine were tested in a total of eight volunteers. Two 120-μg doses were given subcutaneously at 0 and 5 wk. Mild local reactions occurred in all eight volunteers, but no systemic reactions were observed. 2 wk after the first dose, six of the volunteers had increased levels of bactericidal antibodies against both the group B polysaccharide and the outer membrane proteins. Antibody rises to the group B polysaccharide (mean 6-fold) were confirmed by passive hemagglutination assays and rises to the proteins (mean 10-fold) by a solid phase radioimmunoassay. The second dose resulted in little or no increase in antibody titers. Antibody titers declined over a period of 14 wk but mostly remained above preimmunization levels. Bactericidal antibodies with specificity for the group B polysaccharide were mostly of the immunoglobulin (Ig)M class, and were directed against a determinant associated only with high molecular weight polysaccharides. We conclude that both the group B polysaccharide and the outer membrane protein are immunogenic in man when presented as a complex and that the complex warrants further testing and development as a vaccine against group B meningococcal disease.

Full text

PDF
840

Images in this article

Selected References

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

  1. Anderson P., Smith D. H. Immunogenicity in weanling rabbits of a polyribophosphate complex from Haemophilus influenzae type b. J Infect Dis. 1977 Aug;136 (Suppl):S63–S70. doi: 10.1093/infdis/136.supplement.s63. [DOI] [PubMed] [Google Scholar]
  2. Artenstein M. S., Gold R., Zimmerly J. G., Wyle F. A., Branche W. C., Jr, Harkins C. Cutaneous reactions and antibody response to meningococcal group C polysaccharide vaccines in man. J Infect Dis. 1970 Apr;121(4):372–377. doi: 10.1093/infdis/121.4.372. [DOI] [PubMed] [Google Scholar]
  3. Artenstein M. S., Rust J. H., Jr, Hunter D. H., Lamson T. H., Buescher E. L. Acute respiratory disease and meningococcal infection in army recruits. JAMA. 1967 Sep 25;201(13):1004–1007. [PubMed] [Google Scholar]
  4. Berman S., Altieri P. L., Groffinger A., Lowenthal J. P. Pilot-scale production of group a and group C meningococcal polysaccharide immunogens. Infect Immun. 1970 Nov;2(5):640–643. doi: 10.1128/iai.2.5.640-643.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhattacharjee A. K., Jennings H. J., Kenny C. P., Martin A., Smith I. C. Structural determination of the sialic acid polysaccharide antigens of Neisseria meningitidis serogroups B and C with carbon 13 nuclear magnetic resonance. J Biol Chem. 1975 Mar 10;250(5):1926–1932. [PubMed] [Google Scholar]
  6. Bovre K., Holten E., Vik-Mo H., Brondbo A., Bratlid D., Bjark P., Moe P. J. Neisseria meningitidis infections in Northern Norway: an epidemic in 1974-1975 due mainly to group B organisms. J Infect Dis. 1977 Apr;135(4):669–672. doi: 10.1093/infdis/135.4.669. [DOI] [PubMed] [Google Scholar]
  7. Brunk C. F., Leick V. Rapid equilibrium isopycnic CsC1 gradients. Biochim Biophys Acta. 1969 Mar 18;179(1):136–144. doi: 10.1016/0005-2787(69)90129-4. [DOI] [PubMed] [Google Scholar]
  8. Cheng W. C., Webb E., Vedros N., Ng J. Fractionation and characterization of surface antigens from group A Neisseria meningitidis. J Immunol. 1975 May;114(5):1497–1505. [PubMed] [Google Scholar]
  9. Frasch C. E., Chapman S. S. Classification of Neisseria meningitidis group B into distinct serotypes. 3. Application of a new bactericidal-inhibition technique to distribution of serotypes among cases and carriers. J Infect Dis. 1973 Feb;127(2):149–154. doi: 10.1093/infdis/127.2.149. [DOI] [PubMed] [Google Scholar]
  10. Frasch C. E., Chapman S. S. Classification of Neisseria meningitidis group B into distinct serotypes. I. Serological typing by a microbactericidal method. Infect Immun. 1972 Jan;5(1):98–102. doi: 10.1128/iai.5.1.98-102.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frasch C. E., Gotschlich E. C. An outer membrane protein of Neisseria meningitidis group B responsible for serotype specificity. J Exp Med. 1974 Jul 1;140(1):87–104. doi: 10.1084/jem.140.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Frasch C. E., Parkes L., McNelis R. M., Gotschlich E. C. Protection against group B meningococcal disease. I. Comparison of group-specific and type-specific protection in the chick embryo model. J Exp Med. 1976 Aug 1;144(2):319–329. doi: 10.1084/jem.144.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Gold R., Wyle F. A. New Classification of Neisseria meningitidis by Means of Bactericidal Reactions. Infect Immun. 1970 May;1(5):479–484. doi: 10.1128/iai.1.5.479-484.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Goldschneider I., Gotschlich E. C., Artenstein M. S. Human immunity to the meningococcus. II. Development of natural immunity. J Exp Med. 1969 Jun 1;129(6):1327–1348. doi: 10.1084/jem.129.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gotschlich E. C., Goldschneider I., Artenstein M. S. Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J Exp Med. 1969 Jun 1;129(6):1367–1384. doi: 10.1084/jem.129.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gotschlich E. C., Liu T. Y., Artenstein M. S. Human immunity to the meningococcus. 3. Preparation and immunochemical properties of the group A, group B, and group C meningococcal polysaccharides. J Exp Med. 1969 Jun 1;129(6):1349–1365. doi: 10.1084/jem.129.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Griffiss J. M., Bertram M. A., Broud D. D. Separation and purification of immunoglobulins M,A and G from small volumes of human sera by a continuous, inline chromatographic process. J Chromatogr. 1978 Aug 21;156(1):121–130. doi: 10.1016/s0021-9673(00)83132-5. [DOI] [PubMed] [Google Scholar]
  20. Griffiss J. M., Broud D. D., Silver C. A., Artenstein M. S. Immunoepidemiology of meningococcal disease in military recruits. I. A model for serogroup independency of epidemic potential as determined by serotyping. J Infect Dis. 1977 Aug;136(2):176–186. doi: 10.1093/infdis/136.2.176. [DOI] [PubMed] [Google Scholar]
  21. Hill J. C., Weiss E. Protein fraction with immunogenic potential and low toxicity isolated from the cell wall of Neisseria meningitidis group B. Infect Immun. 1974 Sep;10(3):605–615. doi: 10.1128/iai.10.3.605-615.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jennings H. J., Martin A., Kenny C. P., Diena B. B. Cross-protective antigens of Neisseria meningitidis obtained from Slaterus group Y. Infect Immun. 1972 Apr;5(4):547–551. doi: 10.1128/iai.5.4.547-551.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jones D. M., Tobin B. M. Serotypes of group B meningococci. J Clin Pathol. 1976 Aug;29(8):746–748. doi: 10.1136/jcp.29.8.746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kasper D. L., Winkelhake J. L., Brandt B. L., Artenstein M. S. Antigenic specificity of bactericidal antibodies in antisera to Neisseria meningitidis. J Infect Dis. 1973 Apr;127(4):378–387. doi: 10.1093/infdis/127.4.378. [DOI] [PubMed] [Google Scholar]
  25. Kasper D. L., Winkelhake J. L., Zollinger W. D., Brandt B. L., Artenstein M. S. Immunochemical similarity between polysaccharide antigens of Escherichia coli 07: K1(L):NM and group B Neisseria meningitidis. J Immunol. 1973 Jan;110(1):262–268. [PubMed] [Google Scholar]
  26. Kasper D. L., Wyle F. A., Formal S. B. Bactericidal antibody assay using 14 C-labeled Neisseria meningitidis. Proc Soc Exp Biol Med. 1972 Apr;139(4):1175–1180. doi: 10.3181/00379727-139-36324. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Lim D., Gewurz A., Lint T. F., Ghaze M., Sepheri B., Gewurz H. Absence of the sixth component of complement in a patient with repeated episodes of meningococcal meningitis. J Pediatr. 1976 Jul;89(1):42–47. doi: 10.1016/s0022-3476(76)80924-9. [DOI] [PubMed] [Google Scholar]
  29. Maloney P. C., Schneider H., Brandt B. L. Production and degradation of serogroup B Neisseria meningitidis polysaccharide. Infect Immun. 1972 Nov;6(5):657–658. doi: 10.1128/iai.6.5.657-661.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Peltola H., Käyhty H., Kuronen T., Haque N., Sarna S., Mäkelä P. H. Meningococcus group A vaccine in children three months to five years of age. Adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide. J Pediatr. 1978 May;92(5):818–822. doi: 10.1016/s0022-3476(78)80165-6. [DOI] [PubMed] [Google Scholar]
  31. Sivonen A., Renkonen O. V., Robbins J. B. Use of antiserum agar plates for serogrouping of meningococci. J Clin Pathol. 1977 Sep;30(9):834–837. doi: 10.1136/jcp.30.9.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WATSON R. G., SCHERP H. W. The specific hapten of group C (group II alpha) meningococcus. I. Preparation and immunological behavior. J Immunol. 1958 Oct;81(4):331–336. [PubMed] [Google Scholar]
  33. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  34. Wong K. H., Barrera O., Sutton A., May J., Hochstein D. H., Robbins J. D., Robbins J. B., Parkman P. D., Seligmann E. B., Jr Standardization and control of meningococcal vaccines, group A and group C polysaccharides. J Biol Stand. 1977;5(3):197–215. doi: 10.1016/s0092-1157(77)80005-x. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Zollinger W. D., Dalrymple J. M., Artenstein M. S. Analysis of parameters affecting the solid phase radioimmunoassay quantitation of antibody to meningococcal antigens. J Immunol. 1976 Nov;117(5 PT2):1788–1798. [PubMed] [Google Scholar]
  37. Zollinger W. D., Mandrell R. E., Altieri P., Berman S., Lowenthal J., Artenstein M. S. Safety and immunogenicity of a Neisseria meningitidis type 2 protein vaccine in animals and humans. J Infect Dis. 1978 Jun;137(6):728–739. doi: 10.1093/infdis/137.6.728. [DOI] [PubMed] [Google Scholar]
  38. Zollinger W. D., Mandrell R. E. Outer-membrane protein and lipopolysaccharide serotyping of Neisseria meningitidis by inhibition of a solid-phase radioimmunoassay. Infect Immun. 1977 Nov;18(2):424–433. doi: 10.1128/iai.18.2.424-433.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zollinger W. D., Pennington C. L., Artenstein M. S. Human antibody response to three meningococcal outer membrane antigens: comparison by specific hemagglutination assays. Infect Immun. 1974 Nov;10(5):975–984. doi: 10.1128/iai.10.5.975-984.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES