LAUSR

BACKGROUND Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). It is widely accepted that the development and progression of MS result from aberrant activation of potentially encephalitogenic reactive-T cells against CNS antigens. The pathologic roles of both CD4+ (T helper; Th) and CD8+ T cells have been demonstrated in MS lesions. OBJECTIVE In the present work, we applied a series of bioinformatics tools to design a dendritic cell (DC)-targeting Tregitope-based multi-epitope vaccine for MS to induce tolerance in pathogenic myelin-specific T cells. METHODS The 3 D structure of anti-DEC 205 scFv and the remaining part of the vaccine were modeled by ROSIE Antibody server and ITASSER software, respectively. AIDA webserver (ab initio domain assembly server) was applied to assemble two parts of the vaccine and build the full construct. Following modeled structure refinement and validation, physicochemical properties, and allergenicity of vaccine were assessed. In the final step, in silico cloning was done to ensure high-level expression in the desired host. RESULTS This vaccine consists of three main parts; 1) Anti-DEC 205 scFv antibody, 2) multi-epitope vaccine part composed of multiple pathogenic CD4+, and CD8+ T cell epitopes originated from multiple known antigens in MS patients, as well as T-regulatory (Treg)-inducing epitopes (Tregitopes), and 3) vasoactive intestinal peptide (VIP). All parts of the final vaccine were joined together by the helping of proper linkers. After vaccine construction, the three-D structure, as well as different physicochemical and immunological features of the vaccine were predicted. Finally, in silico gene cloning was also carried out to assure efficient production of protein vaccine in Escherichia coli K 12 expression strain. CONCLUSION Computational analysis demonstrated that this vaccine, by harnessing pathogenic T cells, can control MS disease progression and even disease relapse.