LNP-mRNA vaccine prevents type 1 diabetes in non-obese diabetes mice

Islet-antigen-specific tolerization is a key goal of experimental immunotherapies for type 1 diabetes. mRNA-based vaccines have demonstrated the feasibility of RNA delivery in inducing antigen tolerance in autoimmune diseases. In this study, mRNA vaccine, encoded tandem glutamic acid decarboxylase 65 (GAD65) epitopes and cholera toxin B subunit (CTB-GADIII), prepared by an in vitro transcription (IVT) system and encapsulated with lipid nanoparticles (LNP), was intramuscularly administered to nonobese diabetic (NOD) and Cyclophosphamide (Cy)-NOD mice respectively. The results showed that the mRNA vaccines significantly reduced the incidence rate of type 1 diabetes, delayed the disease progression, improved glucose tolerance, and protected pancreatic morphology and function compared with the controls. Meanwhile, the vaccines also reduced the levels of autoantibodies to glutamic acid decarboxylase (GADA) and insulin (IAA) in the serum. Furthermore, the proportion of CD4