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WU Yiling, YOU Qi, WU Jie. Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice[J]. Journal of China Pharmaceutical University, 2021, 52(5): 614-621. DOI: 10.11665/j.issn.1000-5048.20210515
Citation: WU Yiling, YOU Qi, WU Jie. Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice[J]. Journal of China Pharmaceutical University, 2021, 52(5): 614-621. DOI: 10.11665/j.issn.1000-5048.20210515
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Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice

  • School of Life Science and Technology, China Pharmaceutical University,Nanjing 211198, China

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  • Received Date: March 23, 2021
  • Revised Date: May 16, 2021
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    • Abstract
  • To investigate the therapeutic effect of oral vaccine based on glutamate decarboxylase 65 (GAD65) on streptozotocin (STZ) -induced type 1 diabetic (T1D) mice, the mice model of T1D was established by intraperitoneal injection of low dose multiple STZ. CTB-GADIII encapsulated with calcium alginate (Ca-Alg-GADIII) was formulated using crosslinking technology with sodium alginate and calcium chloride, and was administered intragastric to T1D mice once a week for 5 consecutive weeks.Blood glucose and body weight of the mice were recorded weekly, and pharmacodynamics against T1D of Ca-Alg-GADIII were investigated by glucose tolerance assay (OGTT) and pancreatic histopathological analysis. The levels of glutamic acid decarboxylase antibody (GADA), and insulin autoantibody (IAA) and related cytokines (IL-4, IFN-γ, TGF-β1) in serum were detected by ELISA, and the CD4 + T cell subsets were detected by flow cytometry. The immunological mechanism of oral vaccine against T1D was preliminarily discussed. The results showed that the disease-related indicators improved in immunized mice: fasting blood glucose improved, glucose tolerance and insulin secretion increased, pancreatic injury decreased, autoantibodies like GADA and IAA titers significantly decreased, and CD4 + T cell immune balance in mesenteric lymph node (MLN) and pancreatic lymph node (PLN) improved to some extent. The results suggest that oral vaccine Ca-Alg-GADIII has some therapeutic effect on STZ-induced T1D mice.
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