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Clinical and Developmental Immunology
Volume 2013, Article ID 578786, 16 pages
http://dx.doi.org/10.1155/2013/578786
Research Article

Persistent Suppression of Type 1 Diabetes by a Multicomponent Vaccine Containing a Cholera Toxin B Subunit-Autoantigen Fusion Protein and Complete Freund’s Adjuvant

1Center for Health Disparities and Molecular Medicine, Department of Biochemistry, School of Medicine, Loma Linda University, 11085 Campus Street, Loma Linda, CA 92350, USA
2Department of Immunology, Central Veterinary Institute, Tábornok u. 2, 1143 Budapest, Hungary

Received 5 July 2013; Revised 24 August 2013; Accepted 26 August 2013

Academic Editor: Lenin Pavón

Copyright © 2013 Béla Dénes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Libby, D. M. Nathan, K. Abraham et al., “Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on cardiovascular complications of type 1 diabetes mellitus,” Circulation, vol. 111, no. 25, pp. 3489–3493, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. E. A. M. Gale, “The rise of childhood type 1 diabetes in the 20th century,” Diabetes, vol. 51, no. 12, pp. 3353–3361, 2002. View at Google Scholar · View at Scopus
  3. M. Rewers, J. M. Norris, G. S. Eisenbarth et al., “Beta-cell autoantibodies in infants and toddlers without IDDM relatives: diabetes autoimmunity study in the young (DAISY),” Journal of Autoimmunity, vol. 9, no. 3, pp. 405–410, 1996. View at Publisher · View at Google Scholar · View at Scopus
  4. E. A. M. Gale, P. J. Bingley, G. S. Eisenbarth, M. J. Redondo, K. O. Kyvik, and J. S. Petersen, “Reanalysis of twin studies suggests that diabetes is mainly genetic,” British Medical Journal, vol. 323, no. 7319, pp. 997–998, 2001. View at Google Scholar · View at Scopus
  5. H. S. Jun and J. W. Yoon, “The role of viruses in Type I diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals,” Diabetologia, vol. 44, no. 3, pp. 271–285, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. H. K. Åkerblom, O. Vaarala, H. Hyöty, J. Ilonen, and M. Knip, “Environmental factors in the etiology of type 1 diabetes,” American Journal of Medical Genetics, vol. 115, no. 1, pp. 18–29, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. E. Mariño and S. T. Grey, “B cells as effectors and regulators of autoimmunity,” Autoimmunity, vol. 45, no. 5, pp. 377–387, 2012. View at Google Scholar
  8. J. A. Bluestone, K. Herold, and G. Eisenbarth, “Genetics, pathogenesis and clinical interventions in type 1 diabetes,” Nature, vol. 464, no. 7293, pp. 1293–1300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. B. Denes, V. Krausova, N. Fodor et al., “Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens,” Journal of Immunotherapy, vol. 28, no. 5, pp. 438–448, 2005. View at Google Scholar · View at Scopus
  10. B. Dénes, I. Fodor, and W. H. R. Langridge, “Autoantigens plus interleukin-10 suppress diabetes autoimmunity,” Diabetes Technology & Therapeutics, vol. 12, no. 8, pp. 649–661, 2010. View at Google Scholar · View at Scopus
  11. M. W. J. Sadelain, H.-Y. Qin, J. Lauzon, and B. Singh, “Prevention of type I diabetes in NOD mice by adjuvant immunotherapy,” Diabetes, vol. 39, no. 5, pp. 583–589, 1990. View at Google Scholar · View at Scopus
  12. J. N. Manirarora, M. M. Kosiewicz, S. A. Parnell, and P. Alard, “APC activation restores functional CD4+CD25+ regulatory T cells in NOD mice that can prevent diabetes development,” PLoS ONE, vol. 3, no. 11, Article ID e3739, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. J. F. Elliott, H.-Y. Qin, S. Bhatti et al., “Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice,” Diabetes, vol. 43, no. 12, pp. 1494–1499, 1994. View at Google Scholar · View at Scopus
  14. C. Aspord and C. Thivolet, “Nasal administration of CTB-insulin induces active tolerance against autoimmune diabetes in non-obese diabetic (NOD) mice,” Clinical and Experimental Immunology, vol. 130, no. 2, pp. 204–211, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Homann, A. Holz, A. Bot et al., “Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/stat6 pathway,” Immunity, vol. 11, no. 4, pp. 463–472, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. O. R. Millington, A. M. Mowat, and P. Garside, “Induction of bystander suppression by feeding antigen occurs despite normal clonal expansion of the bystander T cell population,” Journal of Immunology, vol. 173, no. 10, pp. 6059–6064, 2004. View at Google Scholar · View at Scopus
  17. J. Holmgren, C. Czerkinsky, N. Lycke, and A.-M. Svennerholm, “Strategies for the induction of immune responses at mucosal surfaces making use of cholera toxin B subunit as immunogen, carrier, and adjuvant,” American Journal of Tropical Medicine and Hygiene, vol. 50, no. 5, pp. 42–54, 1994. View at Google Scholar · View at Scopus
  18. J.-B. Sun, B.-G. Xiao, M. Lindblad et al., “Oral administration of cholera toxin B subunit conjugated to myelin basic protein protects against experimental autoimmune encephalomyelitis by inducing transforming growth factor-β-secreting cells and suppressing chemokine expression,” International Immunology, vol. 12, no. 10, pp. 1449–1457, 2000. View at Google Scholar · View at Scopus
  19. N. Kim, K. C. C. Kuang Chuan Cheng, S. S. K. Soon Seog Kwon, R. Mora, M. Barbieri, and T. J. Yoo, “Oral administration of collagen conjugated with cholera toxin induces tolerance to type II collagen and suppresses chondritis in an animal model of autoimmune ear disease,” Annals of Otology, Rhinology and Laryngology, vol. 110, no. 7, pp. 646–654, 2001. View at Google Scholar · View at Scopus
  20. P. A. Phipps, M. R. Stanford, J.-B. Sun et al., “Prevention of mucosally induced uveitis with a HSP60-derived peptide linked to cholera toxin B subunit,” European Journal of Immunology, vol. 33, no. 1, pp. 224–232, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. J.-B. Sun, J. Holmgren, and C. Czerkinsky, “Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 23, pp. 10795–10799, 1994. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Bregenholt, M. Wang, T. Wolfe et al., “The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes,” Scandinavian Journal of Immunology, vol. 57, no. 5, pp. 432–438, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. M.-G. Roncarolo, M. K. Levings, and C. Traversari, “Differentiation of T regulatory cells by immature dendritic cells,” Journal of Experimental Medicine, vol. 193, no. 2, pp. F5–F9, 2001. View at Google Scholar · View at Scopus
  24. H.-Y. Qin, M. W. J. Sadelain, C. Hitchon, J. Lauzon, and B. Singh, “Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice,” Journal of Immunology, vol. 150, no. 5, pp. 2072–2080, 1993. View at Google Scholar · View at Scopus
  25. N. Shehadeh, F. Calcinaro, B. J. Bradley, I. Bruchlim, P. Vardi, and K. J. Lafferty, “Effect of adjuvant therapy on development of diabetes in mouse and man,” The Lancet, vol. 343, no. 8899, pp. 706–707, 1994. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Tsuji, M. Matsumoto, O. Takeuchi et al., “Maturation of human dendritic cells by cell wall skeleton of Mycobacterium boris bacillus Calmette-Guérin: involvement of toll-like receptors,” Infection and Immunity, vol. 68, no. 12, pp. 6883–6890, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Muto, J. Satoh, G. Muto et al., “Effect of long-term treatment with complete Freund's adjuvant on KK-Ay mouse, a model of non-insulin-dependent diabetes mellitus,” Clinical Immunology and Immunopathology, vol. 83, no. 1, pp. 53–59, 1997. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Huppmann, A. Baumgarten, A.-G. Ziegler, and E. Bonifacio, “Neonatal bacille Calmette-Guerin vaccination and type 1 diabetes,” Diabetes Care, vol. 28, no. 5, pp. 1204–1206, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. Diabetes Action Research and Education Foundation, “Diabetes Research Grants-2010, Cure for Type 1 Diabetes Grant no. 269, A program for the cure of type 1 diabetes using a generic drug: phase II,” http://www.diabetesaction.org/site/PageServer?pagename=research10.
  30. A. S. Chong, J. Shen, J. Tao et al., “Reversal of diabetes in non-obese diabetic mice without spleen cell-derived β cell regeneration,” Science, vol. 311, no. 5768, pp. 1774–1775, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. I.-F. Lee, H. Qin, J. Trudeau, J. Dutz, and R. Tan, “Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells,” Journal of Immunology, vol. 172, no. 2, pp. 937–942, 2004. View at Google Scholar · View at Scopus
  32. B. Tian, J. Hao, Y. Zhang et al., “Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy,” Transplantation, vol. 87, no. 2, pp. 198–206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. T. Brusko, C. Wasserfall, K. McGrail et al., “No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes,” Diabetes, vol. 56, no. 3, pp. 604–612, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Freund, “The mode of action of immunologic adjuvants,” Bibliotheca Tuberculosea, no. 10, pp. 130–148, 1956. View at Google Scholar · View at Scopus
  35. D. Ulaeto, P. E. Lacy, D. M. Kipnis, O. Kanagawa, and E. R. Unanue, “A T-cell dormant state in the autoimmune process of nonobese diabetic mice treated with complete Freund's adjuvant,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 9, pp. 3927–3931, 1992. View at Google Scholar · View at Scopus
  36. A. H. A. Razack, “Bacillus Calmette-Guérin and bladder cancer,” Asian Journal of Surgery, vol. 30, no. 4, pp. 302–309, 2007. View at Google Scholar · View at Scopus
  37. D. Mack, W. Höltl, P. Bassi et al., “The ablative effect of quarter dose bacillus Calmette-Guerin on a papillary marker lesion of the bladder,” Journal of Urology, vol. 165, no. 2, pp. 401–403, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. J. R. Broderson, “A retrospective review of lesions associated with the use of Freund's adjuvant,” Laboratory Animal Science, vol. 39, no. 5, pp. 400–405, 1989. View at Google Scholar · View at Scopus
  39. A. Rabinovitch, “An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus,” Diabetes/Metabolism Reviews, vol. 14, no. 2, pp. 129–151, 1998. View at Google Scholar
  40. N. Giarratana, G. Penna, S. Amuchastegui, R. Mariani, K. C. Daniel, and L. Adorini, “A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development,” Journal of Immunology, vol. 173, no. 4, pp. 2280–2287, 2004. View at Google Scholar · View at Scopus
  41. A. P. Martin, M. G. Grisotto, C. Canasto-Chibuque et al., “Islet expression of M3 uncovers a key role for chemokines in the development and recruitment of diabetogenic cells in NOD mice,” Diabetes, vol. 57, no. 2, pp. 387–394, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. Z. Yi, R. Diz, A. J. Martin et al., “Long-term remission of diabetes in NOD mice is induced by nondepleting anti-CD4 and anti-CD8 Antibodies,” Diabetes, vol. 61, no. 11, pp. 2871–2880, 2012. View at Google Scholar
  43. M. B. A. Oldstone, “Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence,” Journal of Experimental Medicine, vol. 171, no. 6, pp. 2077–2089, 1990. View at Publisher · View at Google Scholar · View at Scopus
  44. H.-S. Jun, Y.-H. Chung, J. Han et al., “Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase,” Diabetologia, vol. 45, no. 5, pp. 668–676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Moss, “Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 21, pp. 11341–11348, 1996. View at Publisher · View at Google Scholar · View at Scopus
  46. N. L. Yates and M. A. Alexander-Miller, “Vaccinia virus infection of mature dendritic cells results in activation of virus-specific naïve CD8+ T cells: a potential mechanism for direct presentation,” Virology, vol. 359, no. 2, pp. 349–361, 2007. View at Publisher · View at Google Scholar · View at Scopus