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Chemically Modified Capsular Polysaccharides as Vaccines

  • H. J. Jennings
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 228)

Abstract

Vaccination is one of the most useful scientific developments in the control and eradication of human disease. Early vaccines were based on whole organism preparations which, although efficacious in some cases (smallpox), had disadvantages which severely limited their general use. Because of the complexity of bacteria, it is difficult to maintain consistency of potency in terms of immunological protection, and, more importantly, to avoid severe toxic or other deleterious effects caused by indigenous component molecules (lipopolysaccharide or peptidoglycan) of some pathogenic bacteria. The discoveries of a “specific soluble substance” secreted by Pneumococci during growth1 and the immunogenicity of these substances (capsular polysaccharides)2 were new and important developments in vaccine technology. It was demonstrated3 that this substance was in fact a type-specific polysaccharide that was able to quantitatively precipitate4 antibodies produced in animals by injection of the homologous, whole organisms. In subsequent pioneering work5 it was demonstrated that when used as human vaccines these purified polysaccharides provide type-specific protection against the development of pneumococcal infection. However, at this critical stage of development the phenomenal success of antibiotic therapy for treating bacterial infections overshadowed the early promise of polysaccharide vaccines.

Keywords

Sialic Acid Nuclear Magnetic Resonance Spectroscopy Tetanus Toxoid Capsular Polysaccharide Neisseria Meningitidis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Dochez, A. R. and Avery, O.T. (1917). The elaboration of specific soluble substance by Pneumococcus during growth. J. Exp. Med. 26:477–493.PubMedCrossRefGoogle Scholar
  2. 2.
    Francis, T. Jr. and Tillet, W.S. (1930). Cutaneous reactions in pneumonia. The development of antibodies following the intradermal infection of type-specific polysaccharide. J. Exp. Med. 52: 573–585.PubMedCrossRefGoogle Scholar
  3. 3.
    Heidelberger, M. and Avery O.T. (1923). Soluble specific substance of Pneumococcus. J. Exp. Med. 38:73–79.PubMedCrossRefGoogle Scholar
  4. 4.
    Heidelberger, M. and Kendall, F.E. (1935). Soluble specific substance of Pneumococcus III. A quantitative study and a theory of the reaction mechanism. J. Exp. Med. 61:563–591.PubMedCrossRefGoogle Scholar
  5. 5.
    McLeod, C.M., Hodges, R.G., Heidelberger, M. and Bernhard, W.G. (1945). Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med. 82:445–465.CrossRefGoogle Scholar
  6. 6.
    Robbins, J.B. (1978). Vaccines for the prevention of encapsulated bacterial diseases: Current status, problems and prospects for the future. Immunochemistry 15:839–854.PubMedCrossRefGoogle Scholar
  7. 7.
    Jennings, H.J. (1983). Capsular polysaccharides as human vaccines. Adv. Carbohydr. Chem. Biochem., 41: 155–2 08.Google Scholar
  8. 8.
    Finland, M. (1979). Emergence of antibiotic resistance in hospitals. Rev. Infect. Dis. 1:4–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Sell, H.W., Merrill, R.E., Dayne, O.E. and Zimsky, E.P. (1972). Long term sequelae of Haemophilus influenzae meningitis. Pediatrics 49:206–211.PubMedGoogle Scholar
  10. 10.
    Austrian, R. (1976). Vaccines of pneumococcal capsular polysaccharides and the prevention of pneumococcal pneumonia. In The Role of Immunological Factors in Infectious, Allergic and Autoimmune Processes. (Edited by Beers, R.F. Jr. and Bassett, E.G.). pp. 79–89. Raven Press, New York.Google Scholar
  11. 11.
    Bishop, C.T. and Jennings, H.J. (1982). Immunology of polysaccharides. In The Polysaccharides. (Edited by Aspinall, G.O.). pp. 291–330. Academic Press, New York.Google Scholar
  12. 12.
    Wyle, F.A., Artenstein, M.S., Brandt, D.L., Tramont, D.L., Kasper, D.L., Altieri, P., Berman, S.L. and Lowenthal, J.P. (1972). Immunologic response of man to group B meningococcal polysaccharide vaccines. J.Infect. Dis. 126:514–522.PubMedCrossRefGoogle Scholar
  13. 13.
    Gotschlich, E.C., Goldschneider, I., Lepow, M.L. and Gold, R. (1977). The immune responses to bacterial polysaccharides in man. In Antibodies in Human Diagnosis and Therapy. (Edited by Haber, E. and Krause, R.M.). pp. 391–402. Raven Press, New York.Google Scholar
  14. 14.
    Jennings, H.J., Katzenellenbogen, E., Lugowski, C., Michon, F., Roy, R. and Kasper, D.L. (1984). Structure, conformation and immunology of sialic acid-containing polysaccharides of human pathogenic bacteria. Pure Appl. Chem. 56:893–905.CrossRefGoogle Scholar
  15. 15.
    Jennings, H.J., Bhattacharjee, A.K., Bundle, D.R., Kenny, C.P., Martin, A. and Smith, I.C.P. (1977). Structures of the capsular polysaccharides of Neisseria meningitidis as determined by carbon-13 NMR spectroscopy. J. Infect. Dis. Suppl. 136:S78-S83.PubMedCrossRefGoogle Scholar
  16. 16.
    Egan, W. (1980). Structure of the capsular polysaccharide antigens from Haemophilus influenzae and Neisseria meningitidis by 13C NMR spectroscopy. In Magnetic Resonance in Biology. (Edited by Cohen, J.S.). pp.197–258. Wiley, New York.Google Scholar
  17. 17.
    Bax, A., Egan, W. and Kovac, P. (1984). New NMR techniques for structure determination and resonance assignments of complex carbohydrates. J. Carbohydr. Chem. 3:593–611.CrossRefGoogle Scholar
  18. 18.
    Kenne, L. and Lindberg, B. (1983). Bacterial polysaccharides. In The Polysaccharides. (Edited by Aspinall, G.O.). pp. 277–363. Academic Press, New York.Google Scholar
  19. 19.
    Bundle, D.R., Smith, I.C.P. and Jennings, H.J. (1974). Determination of the structure and conformation of bacterial polysaccharides by carbon-13 nuclear magnetic resonance. J. Biol. Chem. 249:2275–2281.PubMedGoogle Scholar
  20. 20.
    Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A. and Smith, I.C.P. (1975). Structural determination of the sialic acid polysaccharide antigens of Neisseria meningitidis serogroup B and serogroup C with carbon- 13 NMR. J. Biol. Chem. 250:1926–1932.PubMedGoogle Scholar
  21. 21.
    Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A. and Smith, I.C.P. (1976). Structural determination of the polysaccharide antigens of Neisseria meningitidis serogroups Y, W-135 and BO. Can. J. Biochem. 54:1–8.PubMedGoogle Scholar
  22. 22.
    Crisel, R.M., Baker, R.S. and Dorman, D.E. (1975). Capsular polymer of Haemophilus influenzae type b. Part. 1. Structural characterization of the capsular polymer of strain Eagan. J. Biol. Chem. 250:4926–4930.PubMedGoogle Scholar
  23. 23.
    Branefors-Helander, P., Erbing, C., Kenne, L. and Lindberg, B. (1976). Structural studies of the capsular antigen form Haemophilus influenzae type b. Acta. Chem. Scand. Ser. B. 30:276–277.CrossRefGoogle Scholar
  24. 24.
    Rebers, P.A. and Heidelberger, M. (1961). The specific polysaccharide of type VI Pneumococcus. II. The repeating unit. J. Am. Chem. Soc. 83:3056–305 9.Google Scholar
  25. 25.
    Jennings, H. J., Katzenellenbogen, E., Lugowski, C. and Kasper, D.L. (1983). Structure of native polysaccharide antigens of types la and lb groups B Streptococcus. Biochemistry 22: 1258–1264.PubMedCrossRefGoogle Scholar
  26. 26.
    Jennings, H. J., Rosell, K. -G., Katzenellenbogen, E. and Kasper, D.L. (1983). Structural determination of the capsular polysaccharide antigen of type II group B Streptococcus. J. Biol. Chem. 258:1793–1798.PubMedGoogle Scholar
  27. 27.
    Jennings, H.J., Rosell, K.-G. and Kasper, D.L. (1980) Structural determination and serology of the native polysaccharide antigen of type III group B Streptococcus. Can. J. Biochem. 58:112–120.PubMedCrossRefGoogle Scholar
  28. 28.
    Vliegenthart, J.F.G., Dorland, L. and van Halbeek, H. (1983). High resolution 1H-nuclear magnetic resonance spectroscopy as a tool in the structural analysis of carbohydrates related to glycoproteins. Adv. Carbohy. Chem. Biochem. 41:209–374.CrossRefGoogle Scholar
  29. 29.
    Michon, F., Brisson, J.R., Roy, R., Ashton, F.E. and Jennings, H.J. (1985). Structural determination of the capsular polysaccharide of Neisseria meningitidis group I: A 2D-NMR analysis. Biochemistry 24:5592–5598.PubMedCrossRefGoogle Scholar
  30. 30.
    Michon, F., Brisson, J.R., Roy, R., Ashton, F.E. and Jennings, H.J. (1985). Structural determination of the capsular polysaccharide of Neisseria meningitidis group K: A 2D-NMR analysis. Can. J. Chem. 63:2781–2786.CrossRefGoogle Scholar
  31. 31.
    Fearon, D.T. (1978). Regulation by membrane sialic acid of ß-1H dependent decay dissociation of amplification complement C-3 convertase of the alternative complement pathway. Proc. Natl. Acad. Sci. 75:1971–1975.PubMedCrossRefGoogle Scholar
  32. 32.
    Edwards, M.S., Kasper, D.L., Jennings, H.J. Baker, C.J. and Nicholson-Weller, A. (1982). Capsular sialic acid prevents activation of the alternative complement pathway by type III group B Streptococci. J. Immunol. 128:1278–1283.PubMedGoogle Scholar
  33. 33.
    Sadler, J.E., Paulson, J.C. and Hill, R.L. (1979). The role of sialic acid in the expression of human MN blood group antigens. J. Biol. Chem. 254:2112–2119.PubMedGoogle Scholar
  34. 34.
    Spik, G., Bayard, B., Fournet, B., Streker, G., Bouquelet, S. and Montreuil, J. Studies on glycoconjugates. Part 64. Complete structure of two carbohydrate units of human serotransferrin. FEBS Lett. 50:296–299.Google Scholar
  35. 35.
    Kornfield, R. and Kornfield, S. (1980). Structure of glycoproteins and their oligosaccharide units. In The Biochemistry of Glycoproteins and Proteoglycans. pp. 1–34. (Edited by Lennarz, W.J.). Plenum, New York.Google Scholar
  36. 36.
    Finne, J., Leinoren, M. and Mäkelä, P.H. (1983). Antigenic similarity between brain components and bacteria causing meningitis. Lancet 2: (8346) 355–357.PubMedCrossRefGoogle Scholar
  37. 37.
    Lui, T.-Y., Gotschlich, E.C., Egan, W. and Robbins, J.B. (1977). Sialic acid-containing polysaccharides ofNeisseria meningitidis and Escherichia coli strain BOS-12 structure and immunology. J. Infect. Dis. Suppl. 136:S71-S77.Google Scholar
  38. 38.
    Gotschlich, E.C., Lui, T.-Y. and Artenstein, M.S. (1969). Human immunity to the meningococcus. Part 3. Preparation and immunochemical properties of the groups A, B and C meningococcal polysaccharides. J. Exp. Med. 129:1349–1365.PubMedCrossRefGoogle Scholar
  39. 39.
    Gotschlich, E.C., Fraser, B.A., Nashimura, O., Robbins, J.B. and Lui, T.-Y. (1981). Lipid on capsular polysaccharides of gram negative bacteria. J. Biol. Chem. 256:8915–8921.PubMedGoogle Scholar
  40. 40.
    Goebel, W.F., (1938). Chemo-immunological studies on conjugated carbohydrate-proteins. XII. The immunological properties of an artificial antigen containing cellobiuronic acid. J. Exp. Med. 68:469–484.PubMedCrossRefGoogle Scholar
  41. 41.
    Kabat, E.A. (1961). Kabat and Maye’s Experimental Immunochemistry. 2nd edition, Charles C. Thomas. Springfield, IL.Google Scholar
  42. 42.
    Gelzner, J. and Kabat, E.A. (1964). Specific fractionation of human antidextran antibodies. III. Fractionation of antidextran by sequential extraction with oligosaccharides of increasing chain lengths and attempts at subfractionation. Immunochemistry 1:303–316.CrossRefGoogle Scholar
  43. 43.
    Jann, K. and Westphal, O. (1975). Microbial polysaccharides. In The Antigens . (Edited by Sela, M.). pp.1–125. Academic Press, New York.Google Scholar
  44. 44.
    Jennings, H.J., Lugowski, C. and Kasper, D.L. (1981). Conformational aspects critical to the immuno-specificity of the type III group B streptococcal polysaccharide. Biochemistry 20:4511–4518.PubMedCrossRefGoogle Scholar
  45. 45.
    Jennings, H.J., Roy, R. and Michon, F. (1985). Determinant specificities of the groups B and C polysaccharides of Neisseria meningitidis. J.Immunol. 134 :2651–2657.PubMedGoogle Scholar
  46. 46.
    Berman, E. (1983). Determination of the structure of three oligosaccharides from normal human urine by using 60 MHz carbon-13 NMR spectroscopy. Carbohydr. Res. 118:9–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Kasper, D.L., Baker, C.J., Galdes, B., Katzenellenbogen, E. and Jennings, H.J. (1983). Immunochemical analysis and immunogenicity of the type II Group B streptococcal capsular polysaccharide. J. Clin. Invest. 72:260–269.PubMedCrossRefGoogle Scholar
  48. 48.
    Schifferle, R.E., Jennings, H.J., Wessels, M.R., Katzenellenbogen, E., Roy, R. and Kasper, D.L. (1985). Immunochemical analysis of the type la and lb Group B streptococcal polysaccharides. J. Immunol. In press.Google Scholar
  49. 49.
    Tai, J.Y., Gotschlich, E.C. and Lancefield, R.C. (1979). Isolation of type specific polysaccharide antigen from Group B type lb Streptococci. J. Exp. Med. 149:58–66.PubMedCrossRefGoogle Scholar
  50. 50.
    Egan, W., Liu, T.-Y., Dorow, D., Cohen, J.S., Robbins, J.D., Gotschlich, E.C. and Robbins, J.B. (1977). Structural studies on the sialic acid polysaccharide antigen of Escherichia coli strain BOS-12. Biochemistry 16:3687–3692.PubMedCrossRefGoogle Scholar
  51. 51.
    Finne, J. and Mäkelä, P.H. (1985). Cleavage of the polysialosyl units of brain glycoproteins by a bacteriophage endosilidase. J. Biol. Chem. 260:1265–1270.PubMedGoogle Scholar
  52. 52.
    Mandrell, R.E. and Zollinger, W.D. (1982). Measurement of antibodies to meningococcal group B polysaccharide: low avidity-binding and equilibrium constants. J. Immunol. 129:2172–2178.PubMedGoogle Scholar
  53. 53.
    Baker, P.J., Amsbaugh, D.F., Stashak, P.W., Caldes, G. and Prescott, B. (1981). Regulation of the antibody response to pneumococcal Streptococcus pneumoniae polysaccharide by T derived cells. Rev. Infect. Dis. 3:332–341.PubMedCrossRefGoogle Scholar
  54. 54.
    Yount, W.J., Dorner, M.M., Kunkel, H.J. and Kabat, E.A. (1968). Studies on human antibodies. IV. Selective variations in subgroup composition and genetic markers. J. Exp. Med. 127:633–646.PubMedCrossRefGoogle Scholar
  55. 55.
    Heidelberger, M., Dilapi, M.M., Siegll, M. and Walter, A.W. (1950). Persistence of antibodies in human subjects injected with pneumococcal polysaccharides. J. Immunol. 65 :535–541.PubMedGoogle Scholar
  56. 56.
    Heidelberger, M. (1973). Immunochemistry of bacterial polysaccharides. In Research in Immunochemistry and Immunobiologv. (Edited by Kwapinski, J.B.G.). pp. 1–40. University Park Press, Baltimore.Google Scholar
  57. 57.
    Heidelberger, M. and Nimmich, W. (1973). Immunochemical relationships between bacteria belonging to two separate families: Pneumococci and Klebsiella. Immunochemistry 13:67–80.CrossRefGoogle Scholar
  58. 58.
    Goldschneider, I.M., Lepow, M.L., Gotschlich, E.C., Mauck, F.T., Bache, F. and Randolph, M. (1973). Immunogenicity of group A and Group C meningococcal polysaccharides in human infants. J. Infect. Dis. 128:769–776.PubMedCrossRefGoogle Scholar
  59. 59.
    Guirguis, N., Schneerson, R., Bax, A., Egan, W., Robbins, J.B., Orskov, I., Orskov, E. and El Kholy, A. (1986). Studies on the immunochemistry, epidemiology and structure of K51 and K93 capsular polysaccharides of Escherichia coli cross-reactive with group A meningococcal polysaccharide. J. Exp. Med. In press.Google Scholar
  60. 60.
    Orskov, F., Orskov, I., Sutton, A., Schneerson, R., Wenlii, L., Egan, W., Moff, G.E. and Robbins, J.B. (1979) Form variation in Escherichia coli Kl: determined by Q-acetylation of the capsular polysaccharide. J. Exp. Med. 149 :669–685.PubMedCrossRefGoogle Scholar
  61. 61.
    Schneerson, R.S. and Robbins, J.B. (1975). Induction of serum Haemophilus influenzae type b capsular antibodies in adult volunteers fed cross reacting Escherichia coli 0–75-K-100-H-5. New Engl. J. Med. 292:1093–1096.Google Scholar
  62. 62.
    Schneerson, R., Barrera, O., Sutton, A. and Robbins, J.B. (1980). Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J. Exp. Med. 152:361–376.PubMedCrossRefGoogle Scholar
  63. 63.
    Anderson, P. (1983). Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the non-toxic protein CRM 197. Infect. Immun. 39:233–238.PubMedGoogle Scholar
  64. 64.
    Jennings, H.J. and Lugowski, C. (1981). Immunochemistry of groups A, B and C meningoccocal polysaccharide-tetanus toxoid conjugates. J. Immunol. 127: 1011–1018.PubMedGoogle Scholar
  65. 65.
    Beuvery, E.C., Miedema, F., Van Delft, F. and Haverkamp, J. (1983). Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines. Infect. Immun. 40:39–45.PubMedGoogle Scholar
  66. 66.
    Beuvery, E.C., Kaaden, A.v.d., Kunhai, V. and Leussink, A.B. (1983). Physiochemical and immunological characterization of meningococcal group A polysaccharide-tetanus toxoid conjugates prepared by two methods. Vaccine 1:31–36.PubMedCrossRefGoogle Scholar
  67. 67.
    Chu, C., Schneerson, R., Robbins, J.B. and Rastogi, S.C. (1983). Further studies on the immunogencity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates. Infect. Immun. 40:245–256.PubMedGoogle Scholar
  68. 68.
    Goebel, W.F. and Avery, O.T. (1931). Chemo-immunological studies on conjugated carbohydrate proteins. IV. Synthesis of the p-aminobenzyl ether of the soluble specific substance of type III pneumococcus and its coupling with protein. J. Exp. Med. 54:431–436.PubMedCrossRefGoogle Scholar
  69. 69.
    Avery, O.T. and Goebel, W.F. (1931). Chemo-immunological studies on conjugated carbohydrate proteins. V. Immunological specificity of an antigen prepared by combining the capsular polysaccharide of type III Pneumococcus with foreign protein. J. Exp. Med. 54:437–447.PubMedCrossRefGoogle Scholar
  70. 70.
    Goebel, W.F. (1940). Antibacterial immunity induced by artificial antigens. II. Immunity to experimental pneumococcal infection with antigens containing saccharides of synthetic origin. J. Exp. Med. 72:33–48.PubMedCrossRefGoogle Scholar
  71. 71.
    Jennings, H.J. (1985). Polysaccharides and conjugated polysaccharides as human vaccines. In New Developments in Industrial Polysaccharides. (Edited by Crescenzi, V., Dea, I.C.M. and Stivala, S.S.). pp.325–344. Gordon and Breach Science Publishers, New York. Google Scholar
  72. 72.
    Beuvery, E.C., Jennings, H.J., Roy, R., Kanhai, V., Nagel, J. and Leussink, A.B. (1986). Vaccine potential of meningococcal group C Q-acetylated and non-Q-acetylated polysaccharide-tetanus toxoid conjugates prepared by two procedures. In Ontogeny of Immune Function and Pathogenic Mechanisms Involved in Vaccine Development. (International Symposium on Bacterial Vaccines. Sept. 17–20, 1984. National Institutes of Health, Washington, DC.). (Edited by Robbins, J.B., Sadoff, G., Schneerson, R.S. and Klein, D.) Preger Press, Philadelphia.Google Scholar
  73. 73.
    Mäkelä, O., Peterfy, F., Outschoorn, I.G., Richter, A.W. and Seppälä, I. (1984). Immunogenic properties of α (1–6) dextran, its protein conjugates and conjugates of its breakdown products in mice. Scand. J. Immunol. 19:541–550.PubMedCrossRefGoogle Scholar
  74. 74.
    Lifely, M.R., Gilbert, A.S. and Moreno, C. (1981). Sialic acid polysaccharide antigens of Neisseria meningitidis and Escherichia coli: Esterification between adjacent residues. Carbohydr. Res. 94:193–203.PubMedCrossRefGoogle Scholar
  75. 75.
    Roy, R., Katzenellenbogen, E. and Jennings, H.J. (1984). Improved procedures for the conjugation of oligosaccharides to protein by reductive amination. Can. J. Biochem. 62: 270–275.CrossRefGoogle Scholar
  76. 76.
    Szu, S.C., Zon, G., Schneerson, R. and Robbins, J.B. (1986). Ultrasonic irradiation of bacterial polysaccharides: Characterization of the depolymerized products and some applications of the process. Carbohydr. Res. In press.Google Scholar
  77. 77.
    Anderson, P., Pichichero, M.E. and Insel, R. (1985). Immunization of two-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b. J. Pediatr. 107:346–351.PubMedCrossRefGoogle Scholar
  78. 78.
    Eskola, J., Peltola, H., Mäkelä, P.H., Kayhty, H., Karanko, V., Samuelson, J. and Gordon, L.K. (1985). Antibody levels achieved in infants by course of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine. Lancet 1:(8439) 1184–1186.PubMedCrossRefGoogle Scholar
  79. 79.
    Jennings, H.J., Roy, R. and Gamin, A. (1986). Induction of meningococcal group B polysaccharide-specific I antibodies in mice using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine. J. Immunol. In press.Google Scholar
  80. 80.
    Jennings, H.J., Roy, R. (1985). Enhancement of the immune response to the group B polysaccharride of Neisseria meningitidis by means of its chemical modification. In The Pathogenic Neisseria: Proceedings Of the Fourth International Symposium. (Edited by Schoolnik, G.K.). American Microbiological Society.Google Scholar
  81. 81.
    Zollinger, W.D. and Mandrell, R.E. (1977). Outer-membrane protein and lipopolysaccharide serotyping of Neisseria meningitidis by inhibition of a solid-phase radioimmunoassay. Infect. Immun. 18:424–433.PubMedGoogle Scholar
  82. 82.
    Jennings, H.J., Bhattacharjee, A.K., Kenne, L., Kenny, C.P. and Calver, G. (1980). The R-type lipopoly-saccharides of Neisseria meningitidis. Can. J. Biochem. 58:128–136.PubMedGoogle Scholar
  83. 83.
    Jennings, H.J., Johnson, K.G. and Kenne, L. (1983). The structure of an R-type oligosaccharide core obtained from some lipopolysaccharides of Neisseria meningitidis. Carbohydr. Res. 121:233–242.PubMedCrossRefGoogle Scholar
  84. 84.
    Jennings, H.J., Lugowski, C. and Ashton, F.E. (1984). Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as a route to a potential vaccine against group B Neisseria meningitidis. Infect. Immun. 43 : 407–412.PubMedGoogle Scholar
  85. 85.
    Svensson, S.B. and Lindberg, A.A. (1979). Coupling of acid labile Salmonella specific oligosaccharides to macromolecular carriers. J. Immunol. Methods 25:323–335.CrossRefGoogle Scholar
  86. 86.
    Kundu, S.R., Diego, I., Osovitz, S. and Marcus, D.M. (1985). Glycosphingolipids of human plasma. Arch. Biochem. Biophys. 228: 388–400.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • H. J. Jennings
    • 1
  1. 1.Division of Biological SciencesNational Research Council of CanadaOttawaCanada

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