Persistent Suppression of Type 1 Diabetes by a Multicomponent Vaccine Containing a Cholera Toxin B Subunit-Autoantigen Fusion Protein and Complete Freund’s Adjuvant
Incidence of diabetes in nonobese diabetic (NOD) mice. (a) Comparison of immunological suppression protocols on diabetes onset in NOD mice as determined by increased incidence of hyperglycemia. Treatment with rVV-CTB::GAD alone and coinoculation with CFA demonstrated statistically significant differences (–0.001) compared to the phosphate-buffered saline (PBS) (mock-infected) control group. Differences between CFA (1 : 10), CFA (1 : 100), and PBS treatment groups are statistically insignificant (Mann-Whitney U test). (b) Blood glucose levels in all experimental animal groups were monitored biweekly. Each data point represents the average blood glucose determination for all mice in that group until 105 weeks of age. Starting from 107 weeks of age several mice have died from unknown and unrelated to diabetes reasons; the figure does not show data points between 107 and 119 weeks. By the end of the experiment, highest blood glucose levels were detected in naive mice inoculated with PBS, CFA (1 : 10), and CFA (1 : 100), reaching average levels of 31, 33, and 30 mmol/L, respectively. Lowest levels of blood glucose maintenance were found in NOD mice inoculated with rVV-CTB::GAD + CFA (1 : 0) (18.8 mmol/L), CFA (1 : 0) (21.1 mmol/L), and rVV-CTB::GAD + CFA (1 : 10) (22.2 mmol/L). Differences in the average blood glucose levels in all groups were statistically significant (–0.001) compared to naive controls, except group of mice inoculated with CFA (1 : 100) (Mann-Whitney U test).
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