Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens

B. Dénes, Valentina Krausova, Nadja Fodor, Tatyana Timiryasova, David Henderson, John Hough, Jie Yu, Istvan Fodor, William H R Langridge

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Oral administration of autoantigens and allergens can delay or suppress clinical disease in experimental autoimmune and allergic disorders. However, repeated feeding of large amounts of the tolerogens is required over long periods and is only partially effective in animals systemically sensitized to the ingested antigen. Enhanced suppression of type 1 autoimmune diabetes insulitis and hyperglycemia was demonstrated in both naive and immune animals following oral inoculation with plant-based antigens coupled to the cholera toxin B subunit (CTB). Thus, plant-synthesized antigens linked to the CTB adjuvant, can enhance suppression of inflammatory TH1 lymphocyte-mediated autoreactivity in both naive and immune animals. To stimulate adjuvant-autoantigen fusion protein biosynthesis in the gut mucosae, the authors evaluated oral inoculation of juvenile non-obese diabetic (NOD) mice with recombinant vaccinia virus (rVV) expressing fusion genes encoding CTB linked to the pancreatic islet autoantigens proinsulin (INS) and a 55-kDa C-terminal peptide from glutamate decarboxylase (GAD55). Hyperglycemic in both rVV-CTB:: INS and rVV-CTB:: GAD inoculated mice was substantially reduced in comparison with the uninoculated mouse control. Oral inoculation with rVV carrying the CTB::INS fusion gene generated a significant reduction in insulitis. An increase in IgG1 in comparison with IgG2c antibody isotype titers in rVV-CTB::INS infected mice suggested possible activation of autoantigen specific Th2 lymphocytes. The experimental results demonstrate feasibility of using vaccinia virus oral delivery of adjuvanted autoantigens to the mucosae of prediabetic mice for suppression and therapy of type 1 autoimmune diabetes.

Original languageEnglish
Pages (from-to)438-448
Number of pages11
JournalJournal of Immunotherapy
Volume28
Issue number5
Publication statusPublished - Sep 2005

Fingerprint

Inbred NOD Mouse
Vaccinia virus
Cholera Toxin
Autoantigens
Type 1 Diabetes Mellitus
Plant Antigens
Gene Fusion
Mucous Membrane
Lymphocytes
Proinsulin
Glutamate Decarboxylase
Protein Biosynthesis
Islets of Langerhans
Hyperglycemia
Allergens
Oral Administration
Immunoglobulin G
Antigens
Peptides
Antibodies

Keywords

  • Adjuvant
  • Cholera toxin
  • CTB
  • Diabetes
  • GAD
  • Insulin
  • Vaccinia virus

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Dénes, B., Krausova, V., Fodor, N., Timiryasova, T., Henderson, D., Hough, J., ... Langridge, W. H. R. (2005). Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens. Journal of Immunotherapy, 28(5), 438-448.

Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens. / Dénes, B.; Krausova, Valentina; Fodor, Nadja; Timiryasova, Tatyana; Henderson, David; Hough, John; Yu, Jie; Fodor, Istvan; Langridge, William H R.

In: Journal of Immunotherapy, Vol. 28, No. 5, 09.2005, p. 438-448.

Research output: Contribution to journalArticle

Dénes, B, Krausova, V, Fodor, N, Timiryasova, T, Henderson, D, Hough, J, Yu, J, Fodor, I & Langridge, WHR 2005, '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.
Dénes, B. ; Krausova, Valentina ; Fodor, Nadja ; Timiryasova, Tatyana ; Henderson, David ; Hough, John ; Yu, Jie ; Fodor, Istvan ; Langridge, William H R. / Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens. In: Journal of Immunotherapy. 2005 ; Vol. 28, No. 5. pp. 438-448.
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