■当前的结核病(TB)控制策略面临局限性,如抗生素治疗依从性低和多药耐药性上升。此外,缺乏安全有效的疫苗化合物这些挑战。现有疫苗对结核病的疗效有限,这凸显了创新战略的紧迫性。如免疫信息学。因此,本研究旨在利用免疫信息学方法设计针对结核感染的靶向多表位疫苗.
■针对Ag85A的多表位疫苗,Ag85B,ESAT-6和CFP-10蛋白。该设计采用了细胞毒性T淋巴细胞(CTL)的各种免疫信息学工具,辅助性T淋巴细胞(HTL),和线性B淋巴细胞(LBL)表位预测,对疫苗特性的评估,结构建模,人口覆盖率分析,二硫化物工程,溶解度预测,与Toll样受体(TLRs)的分子对接/动力学,密码子优化/克隆,和免疫模拟。
■多表位疫苗,它是用12个CTL组装的,25HTL,和21个与CpG佐剂相关的LBL表位,表现出了有希望的特点。免疫信息学分析证实了抗原性,免疫原性,缺乏过敏原性。物理化学评估表明蛋白质是稳定的,热稳定,亲水性,并且高度可溶。对接模拟表明与TLR的高亲和力结合,包括TLR2、TLR4和TLR9。计算机免疫模拟预测了强T细胞(细胞因子释放)和B细胞(免疫球蛋白释放)反应。
■这种免疫信息学设计的多表位疫苗靶向Ag85A,Ag85B,ESAT-6和CFP-10蛋白在稳定性方面显示出有希望的特征,免疫原性,抗原性,溶解度,并预测体液和适应性免疫反应的诱导。这表明其作为针对TB的预防性和治疗性疫苗的潜力。
UNASSIGNED: Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach.
UNASSIGNED: The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation.
UNASSIGNED: The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses.
UNASSIGNED: This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.