In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis.
In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis.
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针对结核分枝杆菌的混杂嵌合多表位疫苗的计算机设计
DOI：
10.1016/j.csbj.2023.01.019
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发表时间：
2023
影响因子：
6
通讯作者：
He, Jin
中科院分区：
文献类型：
--
作者：
Andongma, Binda T.;Huang, Yazheng;Chen, Fang;Tang, Qing;Yang, Min;Chou, Shan-Ho;Li, Xinfeng;He, Jin
关键词：
结核病是一种全球健康威胁，每年造成约150万人死亡。由于出现了广泛的耐药菌株，根除结核病的主要病原体结核分枝杆菌越来越具有挑战性。接种疫苗被认为是保护宿主免受病原体侵害的有效方法，但是唯一临床批准的结核病疫苗卡介苗（Bacillus calmetet - gusamrin， BCG）对成人的保护作用有限。多表位疫苗已被发现通过选择性地结合几种候选蛋白的表位来增强对疾病的免疫力。本研究旨在利用免疫信息学方法设计一种抗结核病的多表位疫苗。通过功能富集，我们鉴定出结核分枝杆菌分泌的8种蛋白质，这些蛋白质要么是发病所必需的，要么分泌到细胞外空间，要么两者兼而有之。然后，我们分析了这些蛋白的表位，并选择了16个具有干扰素γ诱导活性的辅助性T淋巴细胞表位，15个细胞毒性T淋巴细胞表位和10个线性b细胞表位，并使用适当的连接物将它们与佐剂和Pan HLA dr结合表位（PADRE）结合。此外，我们预测了该疫苗的三级结构，它与toll样受体-4 （TLR4）的潜在相互作用，以及它可能引发的免疫反应。结果表明，该疫苗对TLR4具有较强的亲和力，能显著刺激CD4+、CD8+细胞分泌免疫因子，刺激B淋巴细胞分泌免疫球蛋白，从而获得良好的体液免疫和细胞免疫。总的来说，这种多表位蛋白被预测为稳定、安全、高抗原性和高免疫原性，有可能作为一种全球结核病疫苗。
Tuberculosis (TB) is a global health threat, killing approximately 1.5 million people each year. The eradication of Mycobacterium tuberculosis, the main causative agent of TB, is increasingly challenging due to the emergence of extensive drug-resistant strains. Vaccination is considered an effective way to protect the host from pathogens, but the only clinically approved TB vaccine, Bacillus Calmette-Guérin (BCG), has limited protection in adults. Multi-epitope vaccines have been found to enhance immunity to diseases by selectively combining epitopes from several candidate proteins. This study aimed to design a multi-epitope vaccine against TB using an immuno-informatics approach. Through functional enrichment, we identified eight proteins secreted by M. tuberculosis that are either required for pathogenesis, secreted into extracellular space, or both. We then analyzed the epitopes of these proteins and selected 16 helper T lymphocyte epitopes with interferon-γ inducing activity, 15 cytotoxic T lymphocyte epitopes, and 10 linear B-cell epitopes, and conjugated them with adjuvant and Pan HLA DR-binding epitope (PADRE) using appropriate linkers. Moreover, we predicted the tertiary structure of this vaccine, its potential interaction with Toll-Like Receptor-4 (TLR4), and the immune response it might elicit. The results showed that this vaccine had a strong affinity for TLR4, which could significantly stimulate CD4+ and CD8+ cells to secrete immune factors and B lymphocytes to secrete immunoglobulins, so as to obtain good humoral and cellular immunity. Overall, this multi-epitope protein was predicted to be stable, safe, highly antigenic, and highly immunogenic, which has the potential to serve as a global vaccine against TB.
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MHC I类的性质提出了增强免疫原性的肽。
影响因子：
4.3
作者：
Calis JJ;Maybeno M;Greenbaum JA;Weiskopf D;De Silva AD;Sette A;Keşmir C;Peters B
通讯作者：
Peters B
结核分枝杆菌免疫逃避的机制是对结核病疫苗设计的挑战。
影响因子：
30.3
作者：
Ernst JD
通讯作者：
Ernst JD
影响因子：
3.6
作者：
Chen, Jeffrey M.;Zhang, Ming;Cole, Stewart T.
通讯作者：
Cole, Stewart T.
影响因子：
7.3
作者：
Dong, Rong;Chu, Zhugang;Zha, Yan
通讯作者：
Zha, Yan
DOI：
10.1080/07391102.2020.1850357
发表时间：
2020-11-16
影响因子：
4.4
作者：
Ayyagari, Vijaya Sai;Venkateswarulu, T. C.;Srirama, Krupanidhi
通讯作者：
Srirama, Krupanidhi