预防潜伏性结核感染的多表位疫苗的设计与研制

Medicine Advances Pub Date : 2023-11-14 DOI:10.1002/med4.40
Fan Jiang, Lingling Wang, Jie Wang, Peng Cheng, Jing Shen, Wenping Gong
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摘要

背景潜伏性结核感染(Latent tuberculosis infection, LTBI)经常发展为活动性结核,需要开发新型疫苗来预防LTBI。在这项研究中,我们旨在设计一种结核分枝杆菌(M. tuberculosis)疫苗,该疫苗可以引发有效的免疫反应来预防LTBI。方法利用生物信息学和免疫信息学技术,研制多表位疫苗(MEV) C624P。该疫苗含有6个细胞毒性T淋巴细胞(CTL)、2个辅助T淋巴细胞(HTL)和4个B细胞表位,这些表位来源于与LTBI和结核分枝杆菌差异区相关的6种抗原。我们在MEV中加入Toll样受体(TLR)激动剂和PADRE肽以增强其免疫原性。分析了C624P疫苗的理化性质、空间结构、与tlr的分子对接以及免疫学特性。结果C624P疫苗具有良好的抗原性和免疫原性,分别为0.901398和3.65609。疫苗结构稳定,α‐螺旋含量为42.82%,Z‐值为−7.84,优化后Ramachandran样区面积为85.84%。分子对接分析表明,C624P疫苗能与TLR2(−1011.0 kcal/mol)和TLR4(−941.4 kcal/mol)紧密结合。此外,C624P疫苗有效刺激T淋巴细胞和B淋巴细胞,导致高水平的Th1细胞因子,如IFN‐γ和IL‐2。结论C624P疫苗是一种很有前景的预防LTBI的MEV。该疫苗具有良好的抗原性、免疫原性、稳定性和激活免疫反应的能力,表明其在预防LTBI方面是有效的。我们的研究证明了生物信息学和免疫信息学技术在设计安全有效的结核病疫苗中的效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection
Abstract Background Latent tuberculosis infection (LTBI) often progresses to active tuberculosis, necessitating the development of novel vaccine to prevent LTBI. In this study, we aimed to design a Mycobacterium tuberculosis ( M. tuberculosis ) vaccine that could elicit a potent immune response to prevent LTBI. Methods We used bioinformatics and immunoinformatics techniques to develop a multi‐epitope vaccine (MEV) called C624P. The vaccine contained six cytotoxic T lymphocytes (CTL), two helper T lymphocytes (HTL), and four B‐cell epitopes derived from six antigens associated with LTBI and the Mycobacterium tuberculosis region of difference. We added Toll‐like receptor (TLR) agonists and PADRE peptide to the MEV to enhance its immunogenicity. We then analyzed the C624P vaccine's physical and chemical properties, spatial structure, molecular docking with TLRs, and immunological features. Results The C624P vaccine displayed good antigenicity and immunogenicity scores of 0.901398 and 3.65609, respectively. The vaccine structure was stable, with 42.82% α‐helix content, a Z‐value of −7.84, and a favored Ramachandran plot area of 85.84% after majorization. Molecular docking analysis showed that the C624P vaccine could bind tightly to TLR2 (−1011.0 kcal/mol) and TLR4 (−941.4 kcal/mol). Furthermore, the C624P vaccine effectively stimulated T and B lymphocytes, resulting in high levels of Th1 cytokines such as IFN‐γ and IL‐2. Conclusions The C624P vaccine represents a promising MEV for preventing LTBI. The vaccine's good antigenicity, immunogenicity, stability, and ability to activate immune responses suggest its effectiveness in preventing LTBI. Our study demonstrated the utility of bioinformatics and immunoinformatics techniques in designing safe and effective tuberculosis vaccines.
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