HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bot, A. Articles by von Herrath, M. Search for Related Content PubMed PubMed Citation Articles by Bot, A. Articles by von Herrath, M.

Plasmid Vaccination with Insulin B Chain Prevents Autoimmune Diabetes in Nonobese Diabetic Mice¹

Adrian Bot^*, Dan Smith^*, Simona Bot^*, Anna Hughes, Tom Wolfe, Lilin Wang^*, Catherine Woods^2,* and Matthias von Herrath^3,

^* Department of Immunology, Alliance Pharmaceutical, San Diego, CA 92121; and Departments of Immunology and Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, CA 92037

The insulin B (InsB) chain bears major type 1 diabetes-associated epitopes of significance for disease in humans and nonobese diabetic (NOD) mice. Somatic expression of InsB chain initiated early in life by plasmid inoculation resulted in substantial protection of female NOD mice against disease. This was associated with a T2 shift in spleen, expansion of IL-4-producing and, to a lesser extent, of IFN--secreting T cells in pancreatic lymph nodes, as well as intermolecular Th2 epitope spreading to glutamic acid decarboxylase determinants. A critical role of IL-4 for the Ag-specific protective effect triggered by plasmid administration was revealed in female IL-4^-/- NOD mice that developed diabetes and higher Th1 responses. Coadministration of IL-4-expressing plasmid or extension of the vaccination schedule corrected the unfavorable response of male NOD mice to DNA vaccination with InsB chain. Thus, plasmid-mediated expression of the InsB chain early in diabetes-prone mice has the potential to prevent transition to full-blown disease depending on the presence of IL-4.

This article has been cited by other articles:

				G. Rajpal, M. Liu, Y. Zhang, and P. Arvan Single-Chain Insulins as Receptor Agonists Mol. Endocrinol., May 1, 2009; 23(5): 679 - 688. [Abstract] [Full Text] [PDF]

				M. von Herrath Can We Learn From Viruses How to Prevent Type 1 Diabetes?: The Role of Viral Infections in the Pathogenesis of Type 1 Diabetes and the Development of Novel Combination Therapies Diabetes, January 1, 2009; 58(1): 2 - 11. [Abstract] [Full Text] [PDF]

				N. Solvason, Y.-P. Lou, W. Peters, E. Evans, J. Martinez, U. Ramirez, A. Ocampo, R. Yun, S. Ahmad, E. Liu, et al. Improved Efficacy of a Tolerizing DNA Vaccine for Reversal of Hyperglycemia through Enhancement of Gene Expression and Localization to Intracellular Sites J. Immunol., December 15, 2008; 181(12): 8298 - 8307. [Abstract] [Full Text] [PDF]

				M. M. Martinic, A. E. Juedes, D. Bresson, D. Homann, K. Skak, C. Huber, E. Ling, M. Ejrnaes, T. Wolfe, L. Togher, et al. Minimal Impact of a De Novo-Expressed {beta}-Cell Autoantigen on Spontaneous Diabetes Development in NOD Mice Diabetes, April 1, 2007; 56(4): 1059 - 1068. [Abstract] [Full Text] [PDF]

				G. Marodon, S. Fisson, B. Levacher, M. Fabre, B. L. Salomon, and D. Klatzmann Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors Blood, November 1, 2006; 108(9): 2972 - 2978. [Abstract] [Full Text] [PDF]

				B. Faideau, E. Larger, F. Lepault, J. C. Carel, and C. Boitard Role of {beta}-Cells in Type 1 Diabetes Pathogenesis Diabetes, December 1, 2005; 54(suppl_2): S87 - S96. [Abstract] [Full Text] [PDF]

				P. P. Ho, P. Fontoura, M. Platten, R. A. Sobel, J. J. DeVoss, L. Y. Lee, B. A. Kidd, B. H. Tomooka, J. Capers, A. Agrawal, et al. A Suppressive Oligodeoxynucleotide Enhances the Efficacy of Myelin Cocktail/IL-4-Tolerizing DNA Vaccination and Treats Autoimmune Disease J. Immunol., November 1, 2005; 175(9): 6226 - 6234. [Abstract] [Full Text] [PDF]

				G. Han, Y. Li, J. Wang, R. Wang, G. Chen, L. Song, R. Xu, M. Yu, X. Wu, J. Qian, et al. Active Tolerance Induction and Prevention of Autoimmune Diabetes by Immunogene Therapy Using Recombinant Adenoassociated Virus Expressing Glutamic Acid Decarboxylase 65 Peptide GAD500-585 J. Immunol., April 15, 2005; 174(8): 4516 - 4524. [Abstract] [Full Text] [PDF]

				P. P. Ho, P. Fontoura, P. J. Ruiz, L. Steinman, and H. Garren An Immunomodulatory GpG Oligonucleotide for the Treatment of Autoimmunity via the Innate and Adaptive Immune Systems J. Immunol., November 1, 2003; 171(9): 4920 - 4926. [Abstract] [Full Text] [PDF]

				C. Seifarth, S. Pop, B. Liu, C. P. Wong, and R. Tisch More Stringent Conditions of Plasmid DNA Vaccination Are Required to Protect Grafted Versus Endogenous Islets in Nonobese Diabetic Mice J. Immunol., July 1, 2003; 171(1): 469 - 476. [Abstract] [Full Text] [PDF]

				W. Karges, K. Pechhold, S. Al Dahouk, I. Riegger, M. Rief, A. Wissmann, R. Schirmbeck, C. Barth, and B. O. Boehm Induction of Autoimmune Diabetes Through Insulin (but Not GAD65) DNA Vaccination in Nonobese Diabetic and in RIP-B7.1 Mice Diabetes, November 1, 2002; 51(11): 3237 - 3244. [Abstract] [Full Text] [PDF]

				P. Halbout, J.-P. Briand, C. Becourt, S. Muller, and C. Boitard T Cell Response to Preproinsulin I and II in the Nonobese Diabetic Mouse J. Immunol., September 1, 2002; 169(5): 2436 - 2443. [Abstract] [Full Text] [PDF]