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Food Plant-Delivered Cholera Toxin B Subunit for Vaccination and Immunotolerization

  • Takeshi Arakawa
  • Jie Yu
  • William H. R. Langridge
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 464)

Abstract

Developments in recombinant DNA technology have enabled molecular biologists to introduce a variety of novel genes into plant species for specific purposes. From crop improvement to vaccine antigen and antibody production, plants are attractive bioreactors for production of recombinant proteins, as their eukaryotic nature often permits appropriate post-translational modification of recombinant proteins to retain native biological activity. The autotrophic growth of plants requires only soil minerals, water, nitrogen, sunlight energy and carbon dioxide for the synthesis of constituent proteins. Furthermore, production of biologically active proteins in food plants provides the advantage of direct delivery through consumption of edible transformed plant tissues. The production of cholera toxin B subunit in potato plants and applications for prevention of infectious and autoimmune disease are explained in this contribution.

Keywords

Cholera Toxin Transgenic Potato Potato Tissue Transgenic Potato Plant Human Milk Protein 
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. Arakawa, T.; Chong, D. K. X.; Merritt, J. L.; Langridge, W. H. R. Expression of cholera toxin B subunit oligomers in transgenic potato plants. Transgenic Res. 1997, 6, 403–413.PubMedCrossRefGoogle Scholar
  2. Arakawa, T.; Chong, D. K. X.; Langridge, W. H. R. Efficacy of a food plant-based oral cholera toxin B subunit vaccine. Nat. Biotechnol. 1998, 16, 292–297.PubMedCrossRefGoogle Scholar
  3. Arondel, V.; Lemieux, B.; Hwang, I.; Gibson, S.; Goodman, H. M.; Somerville, C. R. Map-based cloning of a gene controlling omega-3 fatty acid desaturation in Arabidopsis. Science 1992, 258, 1353–1355.PubMedCrossRefGoogle Scholar
  4. Bergerot, I.; Ploix, C; Petersen, J.; Moulin, V.; Rask, C; Fabien, N.; Lindblad, M.; Mayer, A.; Czerkinsky, C.; Holmgren, J.; Thivolet, C. A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes. Proc. Natl. A cad. Sci. USA 1997, 94, 4610–4614.CrossRefGoogle Scholar
  5. Bordas, M.; Montesinos, C.; Dabauza, M.; Salvador, A.; Roig, L. A.; Serrano, R.; Moreno, V. Transfer of the yeast salt tolerance gene HAL1 to Cucumis mel L. cultivars and in vitro evaluation of salt tolerance. Transgenic Res. 1997, 6,41–50.PubMedCrossRefGoogle Scholar
  6. Challacombe, S.J.; Tomasi, T. B. Systemic tolerance and secretory immunity after oral immunization. J. Exp. Med. 1980, 152, 1459–1472.PubMedCrossRefGoogle Scholar
  7. Chong, D. K. X.; Roberts, W.; Arakawa, T.; Ules, K.; Bagi, G.; S lattery, C. W.; Langridge, W. H. R. Expression of the human milk protein, β-casein in transgenic potato plants. Transgenic Res. 1997, 6, 289–296.PubMedCrossRefGoogle Scholar
  8. Clemens J. D.; Sack, D. A.; Rao, M. R.; Chakraborty, J.; Khan, M. R.; Kay, B.; Ahmed, E; Banik, A. K.; van Loon, F. P. L.; Yunus, M.; Harris, J. R. Evidence that inactivated oral cholera vaccines both prevent and mitigate Vibrio cholerae O1 infections in a cholera-endemic area. J. Infect. Dis. 1992,166, 1029–1034.PubMedCrossRefGoogle Scholar
  9. Clemens J. D., van Loon, F.; Sack, D. A.; Chakraborty, J.; Rao, M. R.; Ahmed, F.; Harris, J. R.; Khan, M. R.; Yunus, M.; Huda, S.; Kay, B. A.; Svennerholm, A.-M.; Holmgren, J. Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera. J. Infect. Dis. 1991, 163, 1235–1242.PubMedCrossRefGoogle Scholar
  10. Czerkinsky, C.; Russell, M. W.; Lycke, N.; Lindblad, M.; Holmgren, J. Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramu-cosal tissues. Infect. Immun. 1989, 57, 1072–1077.PubMedGoogle Scholar
  11. de Neve, M.; de Loose, M.; Jacobs, A.; van Houdt, H.; Kaluza, B.; Weidle, U.; van Montagu, M.; Depicker, A. Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgenic Res. 1993,2,227–237.PubMedCrossRefGoogle Scholar
  12. Dertzbaugh, M.T.; Elson, C. O. Comparative effectiveness of the cholera toxin B subunit and alkaline Phosphatase as carriers for oral vaccines. Infect. Immun. 1993a, 61, 48–55.PubMedGoogle Scholar
  13. Dertzbaugh, M.T.; Elson, C. O. Reduction in oral immunogenicity of cholera toxin B subunit by N-terminal pep-tide addition. Infect. Immun. 1993b, 61, 384–390.Google Scholar
  14. Eisenbarth, G. Type I diabetes mellitus: a chronic autoimmune disease. N. Engl. J. Med. 1986, 314, 1360–1368.PubMedCrossRefGoogle Scholar
  15. Elson, C. O.; Ealding, W. Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J. Immunol. 1984, 132, 2736–2741.PubMedGoogle Scholar
  16. Elson, CO.; Zivny, J. Oral tolerance: a commentary. In Essentials of Mucosal Immunology; Kagnoff, M. F., Ki-yono, H., Eds.; Academic Press: San Diego, California, 1996.Google Scholar
  17. Escher, A.; O’Kane, D, J.; Lee, J.; Szalay, A. A. Bacterial luciferase alpha-beta fusion protein is fully active as a monomer and highly sensitive in vivo to elevated temperature. Proc. Natl. A cad. Sci. USA 1989, 86, 6528–6532.CrossRefGoogle Scholar
  18. Fuhrman, J. A.; Cebra, J. J. Special features of the priming process for a secretory IgA response: B-cell priming with cholera toxin. J. Exp. Med. 1981, 153, 534–544.PubMedCrossRefGoogle Scholar
  19. Fujihashi, K.; McGhee, J. R.; Yamamoto, M.; Hiroi, T.; Kiyono, H. Role of gamma delta T cells in the regulation of mucosal IgA response and oral tolerance. Ann. N. Y. Acad. Sci. 1996, 778, 55–63.PubMedCrossRefGoogle Scholar
  20. Fujita, K.; Finkelstein, R. A. Antitoxic immunity in experimental cholera: comparison of immunity induced perorally and parenterally in mice. J. Infect. Dis. 1972, 125, 647–655.PubMedCrossRefGoogle Scholar
  21. Gill, D.M. The arrangement of subunits in cholera toxin. Biochemistry? 1976, 15. 1242–1248.PubMedCrossRefGoogle Scholar
  22. Gill, D.M.; Meren, R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: Basis of the activation of adenylate cyclase. Proc. Natl. Aead. Sci. USA 1978, 75, 3050–3054.CrossRefGoogle Scholar
  23. Hajishengallis, G.; Hollingshead, S. K.; Koga, T.; Russell, M. W. Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits. J. Immunol. 1995, 154, 4322–4332.PubMedGoogle Scholar
  24. Hancock, W. W.; Polanski, M.; Zhang, J.; Blogg, N.; Weiner, H. L. Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and-10, transforming growth factor-β, and prostaglandin-E. Am. J. Pathol. 1995,147, 1193–1199.PubMedGoogle Scholar
  25. Haq, T. A.; Mason, H. S.; Clements, J. D.; Arntzen, C. J. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 1995, 268, 714–716.PubMedCrossRefGoogle Scholar
  26. Hardy, S. J. S.; Holmgren, J.; Johansson, S. Sanchez, J.; Hirst, T. R. Coordinated assembly of multisubunit proteins: Oligomerization of bacterial enterotoxins in vivo and in vitro. Proc. Natl. Acad. Sci. USA 1988, 85, 7109–7113.PubMedCrossRefGoogle Scholar
  27. Hiatt, A.; Cafferkey, R.; Bowdish, K. Production of antibodies in transgenic plants. Nature 1989, 342, 76–78.PubMedCrossRefGoogle Scholar
  28. Hirst, T. R.; Holmgren, J. Conformation of protein secreted across bacterial outer membranes: a study of entero-toxin translocation from Vibrio cholerae. Proc. Natl. Acad. Sci. USA 1987, 84, 7418–7422.PubMedCrossRefGoogle Scholar
  29. Holmgren, J.; Lycke, N.; Czerkinsky, C. Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector systems. Vaccine 1993, 11, 1179–1184.PubMedCrossRefGoogle Scholar
  30. Host, A.; Jacobsen, H. P.; Halken, S.; Holmenlund, D. The natural history of cow’s milk protein allergy/intolerance. Eur. J. Clin. Nutr. 1995, 49Suppl 1, S13–S18.PubMedGoogle Scholar
  31. Husby, S.; Mestecky, J.; Moldoveanu, Z.; Holland, S.; Elson, C. O. Oral tolerance in humans. T cell but not B cell tolerance after antigen feeding. J. Immunol. 1994, 752, 4663–4670.Google Scholar
  32. Iturriaga, G.; Leyns, L.; Villegas, A.; Gharaibeh, R.; Salamini, F.; Bartels, D. A family of novel myb-related genes from the resurrection plant Craterostigma plantagineum are specifically expressed in callus and roots in response to ABA or desiccation. Plant Mol. Biol. 1996, 32, 707–716.PubMedCrossRefGoogle Scholar
  33. Jackson, R. J.; Fujihashi, K.; Xu-Amano, J.: Kiyono, H.: Elson, C. O.; McGhee, J. R. Optimizing oral vaccines: induction of systemic and mucosal B-cell and antibody responses to tetanus toxoid by use of cholera toxin as an adjuvant. Infect. immun. 1993, 61 4272–4279.PubMedGoogle Scholar
  34. Keeler, S. J.; Maloney, C. L.; Webber, P. Y.; Patterson, C; Hirata, L. T.; Falco, S. G; Rice, J. A. Expression of de novo high-lysine alpha-helical coiled-coil proteins may significantly increase the accumulated levels of lysine in mature seeds of transgenic tobacco plants. Plant Mol. Biol. 1997, 34, 15–29.PubMedCrossRefGoogle Scholar
  35. Kenward, K. D.; Altschuler, M.; Hildebrand, D.; Davies, P. L. Accumulation of type I fish antifreeze protein in transgenic tobacco is cold-specific. Plant Mol. Biol. 1993, 23, 377–385.PubMedCrossRefGoogle Scholar
  36. Khoury, S. J.; Lider, O.; Al-Sabbagh, A.; Weiner, H. L. Suppression of experimental autoimmune encephalomyeli-tis by oral administration of myelin basic protein. Cell. Immunol. 1990, 131, 302–310.PubMedCrossRefGoogle Scholar
  37. Kim, P.-H.; Eckmann, L.; Lee, W.-J.; Han, W.; Kagnoff, M. F. Cholera toxin and cholera toxin B subunit induce IgAswitching through the action of TGF-β .J. Immunol. 1998, 160, 1198–1203.PubMedGoogle Scholar
  38. Koncz, C; Olsson, O.; Langridge, W. H. R.; Schell, J.; Szalay, A. A. Expression and assembly of functional bacterial luciferase in plants. Proc. Natl. Acad. Sci. USA 1987, 84, 131–135.PubMedCrossRefGoogle Scholar
  39. Kozak, M. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribo-somes. Nucleic Acid Res. 1981, 9, 5233–5252.PubMedCrossRefGoogle Scholar
  40. Langridge, W. H. R.; Fitzgerald, K. L.; Koncz, C.; Schell, J.; Szalay, A. A. Dual promoter of Agrobacterium tume-faciens mannopine synthase gene is regulated by plant growth hormones. Proc. Natl. Acad. Sci. USA 1989, 86,3219–3223.PubMedCrossRefGoogle Scholar
  41. Levine, M. M; Nalin, D. R.; Craig, J. P.; Hoover, D.; Bergquist, E. J.; Waterman, D.; Holley, H. P.; Hornick, R. B.; Pierce, N. P.; Libonati, J. P. Immunity of cholera in man: relative role of antibacterial versus antitoxic immunity. Trans. R. Soc. Trop. Med. Hyg. 1979, 73, 3–9.PubMedCrossRefGoogle Scholar
  42. Logemann, E.; Parniske, M.; Hahlbrock, K. Modes of expression and common structural features of the complete Phenylalanine ammonia-lyase gene family in parsley. Proc. Natl. Acad. Sci. USA 1995, 92, 5905–5909.PubMedCrossRefGoogle Scholar
  43. Lycke, N.; Holmgren, J. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology 1986, 59, 301–308.PubMedGoogle Scholar
  44. Lycke, N.; Lindholm, L.; Holmgren, J. IgA isotype restriction in the mucosal but not in the extramucosal immune response after oral immunizations with cholera toxin or cholera B subunit. Int. Arch. Allergy Appl. Immunol. 1983, 72, 119–121.PubMedCrossRefGoogle Scholar
  45. Lycke, N.; Lindholm, L.; Holmgren, J. Cholera antibody production in vitro by peripheral blood lymphocytes following oral immunization of humans and mice. Clin. Exp. Immunol. 1985, 62, 39–47.PubMedGoogle Scholar
  46. Ma, S.-W.; Zhao, D.-L.; Yin, Z.-Q.; Mukherjee, R.; Singh, B.; Qin, H.-Y.; Stiller, C. R.; Jevnikar, A. M. Transgenic plants expressing autoantigens fed to mice to induce oral tolerance. Nat. Med. 1997, 3, 793–796.PubMedCrossRefGoogle Scholar
  47. Ma, J. K.-C.; Hiatt, A.; Hein, M.; Vine, N. D.; Wang, F.; Stabila, P.; van Dolleweerd, C; Mostov, K.; Lehner, T. Generation and assembly of secretory antibodies in plants. Science 1995, 268, 716–719.PubMedCrossRefGoogle Scholar
  48. Mason, H. S.; Ball, J. ML; Shi, J.-J.; Jiang, X.; Estes, M. K.; Arntzen, C. J. Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc. Natl. Acad. Sci. USA 1996, 93,5335–5340.PubMedCrossRefGoogle Scholar
  49. Mason, H. S.; Lam, D. M.-K.; Arntzen, C. J. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA 1992, 89, 11745–11749.PubMedCrossRefGoogle Scholar
  50. McKenzie, S. J.; Halsey, J. F. Cholera toxin B subunit as a carrier protein to stimulate a mucosa! immune response. J. Immunol. 1984, 133, 1818–1824.PubMedGoogle Scholar
  51. Merritt, E. A.; Sarfaty, S.; Akker, F. V.-D.; L’Hoir, G.; Martial, J. A.; Hol, W. G. J. Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide. Protein Sci. 1994, 3, 166–175.PubMedCrossRefGoogle Scholar
  52. Meyer, R. Detection of genetically engineered plants by polymerase chain reaction (PCR) using the FLAVR SAVR tomato as an example. Zeitschrift Fur Lebensmittel-Untersuchung und-Forschung 1995, 201, 583–586.PubMedCrossRefGoogle Scholar
  53. Miller, A.; Lider, O.; Roberts, A. B.; Sporn, M. B.; Weiner, H. L. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor β after antigen-speeific triggering. Proc. Natl. Acad. Sci. USA 1992, 89, 421–425.PubMedCrossRefGoogle Scholar
  54. Mitra, A.; Zhang, Z. Expression of a human lactoferrin cDNA in tobacco cells produces antibacterial protein(s). Plant Physiol. 1994, 106, 977–981.PubMedCrossRefGoogle Scholar
  55. Miyazaki, J.; Ishii, M.; Tashiro, F. Current studies on the identification of susceptibility genes for IDDM in NOD mice. Nippon Rinsho 1994, 52, 2772–2777.PubMedGoogle Scholar
  56. Miyazaki, A.; Hanafusa, T.; Yamada, K.; Miyagawa, J.; Fujino-Kurihara, H.; Nakajima, H.; Nonaka, K.; Tarui, S. Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-öbese diabetic (NOD) mice: a longitudinal study. Clin. Exp. Immunol. 1985, 60, 622–630.PubMedGoogle Scholar
  57. Munro, S.; Pelham, H. R. B. A C-terminal signal preventssecretion of luminal ER proteins. Cell 1987, 48, 899–907.PubMedCrossRefGoogle Scholar
  58. Schön, A.; Freiré, E. Thermodynamics of intersubunit interactions in cholera toxin upon binding to the Oligosaccharide portion of its cell surface receptor, ganglioside GM1. Biochemistry 1989, 28, 5019–5024.PubMedCrossRefGoogle Scholar
  59. Smeda, R. J.; Hasegawa, P. M.; Goldsbrough, P. B.; Singh, N. K.; Weiler, S. C. A serine-to-threonine substitution in the triazine herbicide-binding protein in potato cells results in atrazine resistance without impairing productivity. Plant Physiol. 1993, 103, 911–917.PubMedCrossRefGoogle Scholar
  60. Suh, H.; Hepburn, A. G.; Kriz, A. L.; Widholm, J. M. Structure of the amplified S-enolpyruvylshikimate-3-phos-phate synthase gene in glyphosate-resistant carrot cells. Plant Mol. Biol. 1993, 22, 195–205.PubMedCrossRefGoogle Scholar
  61. Sun, J.-B.; Holmgren, J.; Czerkinsky, C. Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance. Proc. Natl. Acad. Sci. USA 1994, 91, 10795–10799.PubMedCrossRefGoogle Scholar
  62. Sun, J.-B.; Rask, C; Olsson, T.; Holmgren, J.; Czerkinsky, C. Treatment of experimental autoimmune encephalo-myelitis by feeding myelin basic protein conjugated to cholera toxin B subunit. Proc. Natl. Acad. Sci. USA 1996, 93,7196–7201.PubMedCrossRefGoogle Scholar
  63. Sutton, D.W.; Havstad, P. K.; Kemp, J. D. Synthetic cryIIIA gene from Bacillus thuringiensis improved for high expression in plants. Transgenic Res. 1992, 1, 228–236.PubMedCrossRefGoogle Scholar
  64. Svennerholm, L. Interaction of cholera toxin and ganglioside G(M1). Adv. Exp. Med. Biol. 1976, 71, 191–204.PubMedGoogle Scholar
  65. Thanavala, Y.; Yang, Y.-F.; Lyons, P.: Mason, H. S.; Arntzen, C. J. Immunogen i city of transgenic plant-derived hepatitis B surface antigen. Proc. Natl. Acad. Sci. USA 1995, 92, 3358–3361.PubMedCrossRefGoogle Scholar
  66. Tisch, R.; McDevitt, H. Insulin-dependent diabetes mellitus. Cell 1996, 85, 291–297.PubMedCrossRefGoogle Scholar
  67. Trentham, D. E.; Dynesius-Trentham, R. A.; Orav, E. J.; Combitchi, D.; Lorenzo, C; Sewell, K. L.; Hafler, D. A.; Weiner, H. L. Effects of oral administration of type II collagen on rheumatoid arthritis. Science 1993, 261, 1727–1730.PubMedCrossRefGoogle Scholar
  68. Virtanen, S. M.; Rasanen, L.; Aro, A.; Lindstrom, J.; Sippola, H.; Lounamaa, R.; Toivanen, L.; Tuomilehto, J.; Ak-erblom, H. K. Infant feeding in Finnish children less than 7 yr of age with newly diagnosed IDDM. Childhood diabetes in Finland study group. Diabetes Care 1991, 14, 415–417.PubMedCrossRefGoogle Scholar
  69. Virtanen, S. M.; Saukkonen, T.; Savilahti, E.; Ylonen, K.; Rasanen, L.; Aro, A.; Knip, M.; Tuomilehto, J.; Aker-blom, H. K. Diet, cow’s milk protein antibodies and the risk of IDDM in Finnish children. Childhood diabetes in Finland study group. Diabetologia 1994, 37, 381–387.PubMedCrossRefGoogle Scholar
  70. Wandelt, C. I.; Khan, M. R. I.; Craig, S.; Schroeder, H. E.; Spencer, D.; Higgins, T. J. V. Vieil in with carboxy-ter-minal KDEL is retained in the endoplasmic reticulum and accumulates to high levels in the leaves of transgenic plants. Plant J. 1992, 2, 181–192.PubMedGoogle Scholar
  71. Weiner, H. L.; Friedman, A.; Miller, A.; Khoury, S. J.; al-Sabbagh, A.; Santos, L.; Sayegh, M.; Nussenblatt, R. B.; Trentham, D. E.; Hafler, D. A. Oral tolerance: immunologie mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of áutoantigens. Annu. Rev. Immunol. 1994,72,809–837.CrossRefGoogle Scholar
  72. Weiner, H. L.; Mackin, G. A.; Matsui, M.; Orav, E, J.; Khoury, S. J.; Dawson, D. M.; Hafler, D. A. Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science 1993, 259, 1321–1324.PubMedCrossRefGoogle Scholar
  73. Zhang, Z. J.; Davidson, L.; Eisenbarth, G.; Weinen H. L. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc. Natl. Acad. Sci. USA 1991, 88, 10252–10256.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Takeshi Arakawa
    • 1
    • 2
  • Jie Yu
    • 1
    • 2
  • William H. R. Langridge
    • 1
    • 2
    • 3
    • 4
  1. 1.Center for Molecular Biology and Gene TherapySchool of Medicine, Loma Linda UniversityLoma LindaUSA
  2. 2.Department of Microbiology and Molecular GeneticsSchool of Medicine, Loma Linda UniversityLoma LindaUSA
  3. 3.Department of BiochemistrySchool of Medicine, Loma Linda UniversityLoma LindaUSA
  4. 4.Biology and Gene Therapy, School of MedicineLoma Linda UniversityLoma LindaUSA

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