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利用综合免疫信息学方法挖掘基孔肯雅热基因组,设计 B 和 T 细胞多表位亚单位疫苗,以控制基孔肯雅热感染。

Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection.

机构信息

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan 305817, India.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342011, India.

出版信息

Infect Genet Evol. 2018 Jul;61:4-15. doi: 10.1016/j.meegid.2018.03.007. Epub 2018 Mar 10.

Abstract

Chikungunya infection has been a cause of countless deaths worldwide. Due to lack of permanent treatment and prevention of this disease, the mortality rate remains very high. Therefore, we followed an immunoinformatics approach for the development of multi-epitope subunit vaccine which is able to elucidate humoral, cell-mediated and innate immune responses inside the host body. Both structural and non-structural proteins of chikungunya virus were utilized for prediction of B-cell and T-cell binding epitopes along with interferon-γ (IFN-γ) inducing epitopes. The vaccine construct is composed of β-defensin as an adjuvant at the N-terminal followed by Cytotoxic T-Lymphocytes (CTL) and Helper T-Lymphocyte (HTL) epitopes. The same vaccine construct was also utilized for the prediction of B-cell binding epitopes and IFN-γ inducing epitopes. This was followed by the 3D model generation, refinement and validation of the vaccine construct. Later on, the interaction of modeled vaccine with the innate immune receptor (TLR-3) was explored by performing molecular docking and molecular dynamics simulation studies. Also to check the efficiency of expression of this vaccine construct in an expression vector, in silico cloning was performed at the final stage of vaccine development. Further, designed multi-epitope subunit vaccine necessitates experimental and clinical investigation to develop as an immunogenic vaccine candidate.

摘要

基孔肯雅热感染已成为全球无数人死亡的原因。由于缺乏针对这种疾病的永久性治疗和预防方法,死亡率仍然很高。因此,我们采用免疫信息学方法开发了多表位亚单位疫苗,该疫苗能够阐明宿主体内的体液、细胞介导和先天免疫反应。基孔肯雅病毒的结构蛋白和非结构蛋白均用于预测 B 细胞和 T 细胞结合表位以及干扰素-γ(IFN-γ)诱导表位。疫苗构建体由β防御素作为 N 端的佐剂组成,随后是细胞毒性 T 淋巴细胞(CTL)和辅助性 T 淋巴细胞(HTL)表位。相同的疫苗构建体也用于预测 B 细胞结合表位和 IFN-γ 诱导表位。接下来是疫苗构建体的 3D 模型生成、细化和验证。之后,通过进行分子对接和分子动力学模拟研究,探索了模型化疫苗与先天免疫受体(TLR-3)的相互作用。为了检查这种疫苗在表达载体中的表达效率,在疫苗开发的最后阶段进行了计算机模拟克隆。此外,设计的多表位亚单位疫苗需要进行实验和临床研究,以开发为具有免疫原性的疫苗候选物。

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