fa Phytochemistry پژوهشي Research <span style="font-size:14px;"><span style="font-family:Times New Roman;"><span style="line-height:150%"><span new="" roman="" times=""><b><span style="line-height:150%">Objective:</span></b> <span style="line-height:150%">Diabetes mellitus (DM) is a chronic metabolic disorder with a rapidly increasing global prevalence, posing serious health and economic challenges. Current pharmacological treatments often require lifelong administration and may lead to adverse effects or poor patient compliance. This study aimed to design and evaluate a novel peptide-based vaccine targeting the dipeptidyl peptidase-4 (DPP-4) enzyme as an innovative immunotherapeutic approach for the management of diabetes mellitus.</span></span></span><br> <span style="line-height:150%"><span new="" roman="" times=""><b><span style="line-height:150%">Methods:</span></b> <span style="line-height:150%">A multi-epitope vaccine was constructed by combining six cytotoxic T lymphocyte (CTL) epitopes and one helper T lymphocyte (HTL) epitope, integrated with an immunogenic adjuvant sequence. Comprehensive bioinformatics analyses were employed to predict antigenicity, allergenicity, physicochemical characteristics, and structural stability. Molecular docking and molecular dynamics simulations were used to assess vaccine binding affinity and interaction stability with Toll-like receptor 4 (TLR4). Furthermore, in silico immune simulations were conducted to evaluate the predicted immune response.</span></span></span><br> <span style="line-height:150%"><span new="" roman="" times=""><b><span style="line-height:150%">Results:</span></b> <span style="line-height:150%">The designed vaccine exhibited high antigenicity, non-allergenic properties, and favorable physicochemical stability. Docking and dynamics results revealed a strong and stable interaction between the vaccine construct and TLR4. Immune simulations predicted significant activation of both humoral and cell-mediated immune responses.</span></span></span><br> <span style="line-height:150%"><span new="" roman="" times=""><b><span style="line-height:150%">Conclusion:</span></b> <span style="line-height:150%">The proposed DPP-4-targeted peptide vaccine demonstrates strong potential as a novel immunotherapeutic strategy for diabetes mellitus. It could serve as an alternative to conventional treatments by reducing lifelong drug dependency, improving patient adherence, and alleviating the economic burden of the disease.</span></span></span><br> <img alt="" src="./files/site1/images/copuediting.png" style="width: 586px; height: 265px;" ></span></span> Diabetes mellitus, glucagon-like peptide-1, peptide vaccine, Toll-like receptor 4, dipeptidyl peptidase-4 0 0 http://pbp.medilam.ac.ir/browse.php?a_code=A-10-25-82&slc_lang=fa&sid=1 Farnoush Abdi f.abdi@mail.utoronto.ca 10031947532846006106 10031947532846006106 Yes Institute of Medical Science, University of Toronto, Canada Sako Mirzaie s.mirzaie@mail.utoronto.ca 10031947532846006107 10031947532846006107 No Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada