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register hereAs Bacille Calmette-Guérin (BCG) vaccine's effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope vaccine against Mycobacterium tuberculosis using immunoinformatic analysis.

由于卡介苗（BCG）疫苗的有效性仅限于儿童，正在使用多个平台研究新结核病（TB）疫苗的开发，需要一种克服这一限制的新型结核病疫苗。在这项研究中，我们使用免疫信息学分析设计了一种有效的抗结核分枝杆菌多表位疫苗。

First, we selected 11 highly antigenic proteins based on previous research: Ag85A, Ag85B, Ag85C, ESAT-6, MPT64, Rv2660c, TB10.4, HspX, GlfT2, Fas, and IniB. Among these antigens, 10 linear B-cell epitopes, 9 helper T-cell epitopes, and 16 cytotoxic T-cell epitopes were predicted to design the multi-epitope vaccine.

首先，我们根据先前的研究选择了11种高抗原性蛋白：Ag85A，Ag85B，Ag85C，ESAT-6，MPT64，Rv2660c，TB10.4，HspX，GlfT2，Fas和IniB。在这些抗原中，预测有10个线性B细胞表位，9个辅助性T细胞表位和16个细胞毒性T细胞表位可设计多表位疫苗。

To improve the immunogenicity of the candidate vaccine, three different adjuvants, griselimycin, human beta-defensin 3 (HBD3), and 50s ribosomal protein (50sRP), were attached with linker sequences to the vaccine model. The immunogenic, antigenic, allergenic, and physicochemical properties of the resulting designed multi-epitope vaccines were predicted in silico.

为了提高候选疫苗的免疫原性，将三种不同的佐剂格瑞霉素，人β-防御素3（HBD3）和50s核糖体蛋白（50sRP）与接头序列连接到疫苗模型上。在计算机上预测了所得设计的多表位疫苗的免疫原性，抗原性，致敏性和理化性质。

Moreover, 3D structural modeling, refinement, and validation were used to select a model for further evaluation. Molecular docking analysis revealed a consistent and significant binding affinity of the candidate vaccine for toll-like receptors (TLRs), TLR-2, -3, and -4. Immune simulation performed using C-ImmSim demonstrated that three rounds of immunization with multi-epitope vaccines induced a high production of cytokines and immunoglobulins related with both cellular and humoral immune response.

此外，使用3D结构建模，改进和验证来选择模型进行进一步评估。分子对接分析显示候选疫苗对toll样受体（TLR），TLR-2，-3和-4具有一致且显着的结合亲和力。使用C-ImmSim进行的免疫模拟表明，用多表位疫苗进行三轮免疫可诱导与细胞和体液免疫应答相关的细胞因子和免疫球蛋白的大量产生。

Moreover, we constructed vaccine candidate composed of 50sRP and evaluated its immunogenicity in a mouse model. Consequently, this in silico-engineered multi-epitope structure can elicit adaptive immune responses and .

。因此，这种计算机工程多表位结构可以引发适应性免疫反应。