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利用免疫信息学方法研制抗巨型片形吸虫的多表位亚单位疫苗。

Development of multi-epitope driven subunit vaccine against Fasciola gigantica using immunoinformatics approach.

机构信息

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India.

Laboratory for Structural Bioinformatics, Field for Structural Molecular Biology, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.

出版信息

Int J Biol Macromol. 2019 Oct 1;138:224-233. doi: 10.1016/j.ijbiomac.2019.07.024. Epub 2019 Jul 4.

Abstract

Fascioliasis, a serious helminth disease of the livestock population, results from infection with the parasite Fasciola. Despite the alarming increase in drug resistance, a safe and fully effective vaccine for fascioliasis is still not available. In the present study, we employed high-throughput immunoinformatics approaches to design a multi-epitope based subunit vaccine using seven important F. gigantica proteins (cathepsin B, cathepsin L, leucyl aminopeptidase, thioredoxin glutathione reductase, fatty acid binding protein-1, saposin-like protein-2, and 14-3-3 protein epsilon). The CTL, HTL, and B-cell epitopes were selected for designing the vaccine on the basis of their immunogenic behavior and binding affinity. The engineered vaccine showed potential immunogenic efficacy by elaborating the IFN-γ and humoral response. The modeled structure of the vaccine was docked with the toll-like receptor-2 immune receptor, and the molecular dynamics simulation was performed to understand the stability, interaction, and dynamics of the complex. Finally, in silico cloning of the resulting vaccine was performed to create the plasmid construct of vaccine for expression in an appropriate biological system. Experimental evaluation of the designed vaccine construct in an animal model may result in a novel and immunogenic vaccine that may confer protection against F. gigantica infection.

摘要

片形吸虫病是一种严重的家畜寄生虫病,由寄生虫片形吸虫引起。尽管药物耐药性令人担忧,但仍然没有安全有效的片形吸虫病全面疫苗。在本研究中,我们采用高通量免疫信息学方法,使用七种重要的 F. gigantica 蛋白(组织蛋白酶 B、组织蛋白酶 L、亮氨酸氨肽酶、硫氧还蛋白-谷胱甘肽还原酶、脂肪酸结合蛋白-1、类脂转移蛋白-2 和 14-3-3 蛋白 epsilon)设计了一种基于多表位的亚单位疫苗。根据其免疫原性行为和结合亲和力,选择 CTL、HTL 和 B 细胞表位来设计疫苗。该工程疫苗通过阐述 IFN-γ 和体液反应显示出潜在的免疫效力。对疫苗的模型结构进行了与 toll 样受体-2 免疫受体的对接,进行了分子动力学模拟以了解复合物的稳定性、相互作用和动力学。最后,对所得疫苗进行了计算机克隆,以构建用于在适当生物系统中表达的疫苗质粒构建体。在动物模型中对设计的疫苗构建体进行实验评估可能会产生一种新型的免疫原性疫苗,可提供针对 F. gigantica 感染的保护。

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