InsB:9-23 peptide-based immunotherapy for type 1 diabetes; the immunization frequency and the state of the disease can alter the efficacy

Immunization with beta-cell antigens such as insulin has been under intense investigation for T1D prevention. Insulin B:9-23 has been shown in the past to be able to achieve tolerance in non-obese diabetic (NOD) mice but not in all settings tested. In this study we compared the efficacy of B:9-23 to promote tolerance in NOD when given intranasally to mice at different states of the disease (four vs nine week-old) and with different frequencies (three consecutive days every four weeks vs every week). Interestingly, B:9-23 i.n. administration efficacy was dependent on both parameters, showing maximum protective effect when treatments started at a young age with the low frequency protocol being the most efficient. Simulation results provided by ENTELOS suggested also that interventions at an early stage may favor better results, since beta cell loss is not as dramatic and easier to be reversed. Interestingly, increased frequency of Tregs in blood and spleen was measured following B:9-23 i.n. therapeutic prot...