Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Orthopedics, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.
Curr Drug Saf. 2023;18(1):79-92. doi: 10.2174/1574886317666220429105439.
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.
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.
The 3D structure of anti-DEC205 scFv and the remaining part of the vaccine were modeled by ROSIE Antibody server and ITASSER software, respectively. AIDA web server (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 the vaccine were assessed. In the final step, in silico cloning was done to ensure high-level expression in the desired host.
This vaccine consists of three main parts; 1) Anti-DEC205 scFv antibody, 2) multiepitope 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 with the help 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 K12 expression strain.
Computational study revealed that this vaccination can regulate MS disease progression and even relapse by harnessing pathogenic T cells.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性自身免疫性疾病。广泛认为，MS 的发展和进展是由于针对 CNS 抗原的潜在致脑炎反应性 T 细胞的异常激活。CD4+（辅助性 T；Th）和 CD8+T 细胞在 MS 病变中的病理作用已得到证实。
在本工作中，我们应用一系列生物信息学工具设计了一种针对树突状细胞（DC）的靶向 Tregitope 多表位疫苗，用于诱导致病性髓鞘特异性 T 细胞耐受。
抗 DEC205 scFv 的 3D 结构和疫苗的其余部分分别通过 ROSIE Antibody 服务器和 ITASSER 软件进行建模。AIDA 网络服务器（从头域组装服务器）用于组装疫苗的两部分并构建完整结构。在对建模结构进行细化和验证后，评估了疫苗的理化性质和变应原性。在最后一步中，进行了计算机克隆以确保在所需宿主中高水平表达。
该疫苗由三个主要部分组成：1）抗 DEC205 scFv 抗体，2）由多个来自 MS 患者的已知抗原的多个致病性 CD4+和 CD8+T 细胞表位以及 T 调节（Treg）诱导表位（Tregitopes）组成的多表位疫苗部分，以及 3）血管活性肠肽（VIP）。最终疫苗的所有部分都在适当接头的帮助下连接在一起。构建疫苗后，预测了疫苗的三维结构以及不同的理化和免疫学特征。最后，还进行了计算机基因克隆，以确保在大肠杆菌 K12 表达株中有效生产蛋白疫苗。
计算研究表明，这种疫苗可以通过利用致病性 T 细胞来调节 MS 疾病的进展甚至复发。
