Type 2 diabetes mellitus (T2DM) is a worldwide disease that have an impact on individuals of all ages causing micro and macro vascular impairments due to hyperglycemic internal environment. For ultimate treatment to cure T2DM, association of diabetes with immune components provides a strong basis for immunotherapies and vaccines developments that could stimulate the immune cells to minimize the insulin resistance and initiate gluconeogenesis through an insulin independent route. Immunoinformatics based approach was used to design a polyvalent vaccine for T2DM that involved data accession, antigenicity analysis, T-cell epitopes prediction, conservation and proteasomal evaluation, functional annotation, interactomic and in silico binding affinity analysis. We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) Class-I molecules for immune activation to control T2DM. We found 13-epitopes of 9 amino acid residues for multiple alleles of MHC class-I bears significant binding affinity. The downstream signaling resulted by T-cell activation is directly regulated by the molecular weight, amino acid properties and affinity of these epitopes. Each epitope has important percentile rank with significant ANN IC50 values. These high score potential epitopes were linked using AAY, EAAAK linkers and HBHA adjuvant to generate T-cell polyvalent vaccine with a molecular weight of 35.6 kDa containing 322 amino acids residues. In silico analysis of polyvalent construct showed the significant binding affinity (− 15.34 Kcal/mol) with MHC Class-I. This interaction would help to understand our hypothesis, potential activation of T-cells and stimulatory factor of cytokines and GLUT1 receptors. Our system-level immunoinformatics approach is suitable for designing potential polyvalent therapeutic vaccine candidates for T2DM by reducing hyperglycemia and enhancing metabolic activities through the immune system.

中文翻译：

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用于2型糖尿病的多价治疗疫苗：免疫信息学方法，用于研究细胞因子和GLUT1受体的共同刺激。

2型糖尿病（T2DM）是一种全球性疾病，会对所有年龄段的个体产生影响，由于体内血糖过多而导致微血管和大血管受损。对于治疗T2DM的终极治疗，糖尿病与免疫成分的结合为免疫疗法和疫苗的开发提供了坚实的基础，可以刺激免疫细胞使胰岛素抵抗最小化并通过非胰岛素依赖途径启动糖异生。基于免疫信息学的方法用于设计T2DM的多价疫苗，涉及数据访问，抗原性分析，T细胞表位预测，保守和蛋白酶体评估，功能注释，相互作用和计算机内结合亲和力分析。我们发现抗原肽与主要组织相容性复合体（MHC）I类分子的结合亲和力可通过免疫激活来控制T2DM。我们发现MHC I类的多个等位基因的9个氨基酸残基的13个表位具有显着的结合亲和力。T细胞活化导致的下游信号直接受这些表位的分子量，氨基酸性质和亲和力调节。每个表位都有重要的百分位等级，且具有显着的ANN IC50值。使用AAY，EAAAK接头和HBHA佐剂将这些高分值潜在表位连接在一起，以产生分子量为35.6 kDa的322个氨基酸残基的T细胞多价疫苗。在计算机分析中，多价构建体显示与MHC I类具有显着的结合亲和力（− 15.34 Kcal / mol）。这种相互作用将有助于理解我们的假设，T细胞的潜在活化以及细胞因子和GLUT1受体的刺激因子。我们的系统级免疫信息学方法通过降低高血糖症并通过免疫系统增强代谢活性，适合设计T2DM的潜在多价治疗性候选疫苗。