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新型库蚊唾液蛋白聚集体构建针对血液吸食传播病原体感染的多表位亚单位疫苗

Conglomeration of novel Culex quinquefasciatus salivary proteins to contrive multi-epitope subunit vaccine against infections caused by blood imbibing transmitter.

机构信息

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India.

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India.

出版信息

Int J Biol Macromol. 2018 Oct 15;118(Pt A):834-843. doi: 10.1016/j.ijbiomac.2018.06.112. Epub 2018 Jun 25.

DOI:10.1016/j.ijbiomac.2018.06.112
PMID:29953889
Abstract

The southern house vector, Culex quinquefasciatus is the paramount cause of Japanese encephalitis, West Nile fever and Lymphatic Filariasis, which is globally affecting the worldwide population. Many attempts were made by researchers with different perceptions to discover regimen against these aforementioned ailments but the output was not that effectual. Consequently, there is an imminent need to develop very effective and potential treatment against these perilous diseases. Employing immunoinformatic approaches, we have designed the multi-epitope subunit vaccine by exploring salivary proteins of Culex quinquefasciatus, which possess both antigenic and potent immunogenic behaviour. The immunogenic epitopes from the immune cells (B-cell, CTL, and HTL) were predicted and linked together with the help of linkers. Apart from this, at the N-terminal of the construct, an adjuvant was added in order to enhance the immunogenicity of the vaccine. The physiological parameters, antigenicity and allergenicity were also evaluated for the designed vaccine construct. Molecular docking between ligand (vaccine construct) and TLR-4 receptor was performed. Molecular dynamics simulation of the docked complex was performed to identify the stability, patterns, macromolecules interactions and their behaviour. Finally, to ensure the translation and gene expression efficiency of designed construct, insilico restriction cloning was executed into suitable expression vector pET28a.

摘要

南方家蚊,库蚊属,是日本脑炎、西尼罗河热和淋巴丝虫病的主要病因,这些疾病在全球范围内影响着全球人口。研究人员从不同角度进行了许多尝试,以发现针对这些疾病的治疗方法,但效果并不理想。因此,迫切需要开发针对这些危险疾病的非常有效和有潜力的治疗方法。我们采用免疫信息学方法,通过探索库蚊的唾液蛋白,设计了多表位亚单位疫苗,这些蛋白具有抗原性和强大的免疫原性。利用接头将免疫细胞(B 细胞、CTL 和 HTL)的免疫原性表位连接在一起。此外,在构建物的 N 端添加了佐剂,以增强疫苗的免疫原性。还评估了设计的疫苗构建物的生理参数、抗原性和变应原性。进行了配体(疫苗构建物)和 TLR-4 受体之间的分子对接。对接复合物的分子动力学模拟用于确定稳定性、模式、大分子相互作用及其行为。最后,为了确保设计构建物的翻译和基因表达效率,进行了计算机限制克隆到合适的表达载体 pET28a 中。

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