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利用免疫信息学方法,开发一种基于辅助性 T 细胞和 CTL 表位的保守嵌合疫苗,以诱导针对曼氏血吸虫的强烈免疫应答。

Development of a conserved chimeric vaccine based on helper T-cell and CTL epitopes for induction of strong immune response against Schistosoma mansoni using immunoinformatics approaches.

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

出版信息

Int J Biol Macromol. 2019 Dec 1;141:125-136. doi: 10.1016/j.ijbiomac.2019.08.259. Epub 2019 Aug 31.

Abstract

Currently, three recombinant antigens based vaccines are under clinical trials against Schistosomiasis, but there is no vaccine available for prophylaxis or therapeutic. This study was conducted to construct a multi-epitope based vaccine against Schistosoma mansoni via utilizing Sm14, Sm21.7, Sm23, Sm29, Smp80, Sm-CB and SM-TSP-2 antigens. Helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL) and IFN-γ epitopes were predicted. Furthermore, Pan HLA DR-binding epitope was added to the vaccine. Moreover, 50S ribosomal protein L7/L12 of Mycobacterium tuberculosis as a novel TLR4 agonist was applied. The TAT peptide was added to the vaccine to augment intracellular delivery. The selected epitopes were linked together through appropriate linkers and chimeric vaccine was constructed with 617 amino acids with molecular weight of 65.43 kDa. Physico-chemical properties revealed a soluble protein with antigenic and non-allergic properties. Further analyses validated the stability of the construct that was able to interact with TLR4. Immunoinformatics analysis demonstrated the strong potential of constructed vaccine to stimulate T and B-cell mediated immune responses. In summary, obtained data indicated that the proposed vaccine can properly induce both T and B cells immune responses and could possibly be utilized for prophylactic or therapeutic aims in response to infection caused by S. mansoni.

摘要

目前,有三种基于重组抗原的疫苗正在针对血吸虫病进行临床试验,但尚无预防或治疗用疫苗。本研究旨在构建一种基于 Sm14、Sm21.7、Sm23、Sm29、Smp80、Sm-CB 和 SM-TSP-2 抗原的多表位血吸虫病疫苗。预测了辅助性 T 淋巴细胞 (HTL)、细胞毒性 T 淋巴细胞 (CTL) 和 IFN-γ 表位。此外,还添加了 Pan HLA DR 结合表位。此外,还应用了结核分枝杆菌 50S 核糖体蛋白 L7/L12 作为新型 TLR4 激动剂。在疫苗中添加 TAT 肽以增强细胞内传递。通过适当的接头将选定的表位连接在一起,构建了一个具有 617 个氨基酸和 65.43 kDa 分子量的嵌合疫苗。物理化学特性表明该蛋白具有可溶性、抗原性和非过敏性。进一步的分析验证了该构建体的稳定性,该构建体能够与 TLR4 相互作用。免疫信息学分析表明,所构建的疫苗具有刺激 T 和 B 细胞介导的免疫反应的强大潜力。总之,获得的数据表明,所提出的疫苗可以适当诱导 T 和 B 细胞免疫反应,并可能用于预防或治疗由 S. mansoni 引起的感染。

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