Repeated BCG vaccination is more effective than a single dose in preventing diabetes in non-obese diabetic (NOD) mice

Stimulation of the non-obese diabetic (NOD) mouse immune-system with a single bacillus Calmette-Guerin (BCG) vaccination can inhibit the development of diabetes. The optimal dose, and the time and number of vaccinations is still to be clarified. In this study we evaluated the protective effect of repeated BCG vaccinations on preventing diabetes in NOD mice. 17/32 (53%) of the control group, 8/31 (26%) of the single vaccine-treated (at age 35 days) mice, and 7/23 (30%) of the single vaccine-treated (at age 90 days) mice developed diabetes, and none of the repeated BCG vaccination (at age 35 and 90 days, n = 14) animals developed the disease, up to 250 days of age (p < 0.05, compared with controls and each of the single-vaccination groups). While the severity of insulitis was lower in repeatedly BCG-treated mice at age 120 days as compared with controls and single BCG-vaccination groups, we could not detect significant differences in the Intracellular adhesion molecule-1 (ICAM-1) expression between the various groups. There were no differences in weight gain and blood hematocrit between the different groups. Our report demonstrates that repeated BCG vaccination is safe and more effective than a single dose in preventing type I diabetes in NOD mice. This data should be considered in planning new human trials with BCG.