Anticipatory in silico vaccine designing based on specific antigenic epitopes from

The metabolic disorder Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycaemia, causing increased mortality and healthcare burden globally. Recent studies emphasize the impact of metabolites in the gut microbiome on T2DM pathogenesis. One such microbial metabolite, imidazole propionate (Imp) derived from histidine metabolism, is shown to interfere with insulin signalling and other key metabolic processes. The key enzyme urocanate reductase (UrdA) is involved in ImP production. Hence, we propose to develop a novel therapeutic vaccine against the gut microbe producing Imp based on UrdA as a target for treating T2DM using immunoinformatics approach. Antigenic, non-allergic, non-toxic, and immunogenic B cell and T cell potential epitopes were predicted using immunoinformatics servers and tools. These epitopes were adjoined using linker sequences, and to increase immunogenicity, adjuvants were added at the N-terminal end of the final vaccine construct. Further, to confirm the vaccine's safety, antigenic and non-allergic characteristics of the developed vaccine construct were assessed. The tertiary structure of the UrdA vaccine sequence was predicted using molecular modelling tools. A molecular docking study was utilized to understand the vaccine construct interaction with immune receptors, followed by molecular dynamics simulation and binding free energy calculations to assess stability of the complex. In silico cloning techniques were employed to evaluate the expression and translation effectiveness of the developed vaccine in pET vector. In conclusion, this study developed an in silico epitope-based vaccine construct as a novel adjunct therapeutic for T2DM. Graphical Abstract: