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利用结构和非结构病毒蛋白设计多表位亚单位疫苗以预防 Epstein-Barr 病毒相关恶性肿瘤。

Contriving multiepitope subunit vaccine by exploiting structural and nonstructural viral proteins to prevent Epstein-Barr virus-associated malignancy.

机构信息

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

出版信息

J Cell Physiol. 2019 May;234(5):6437-6448. doi: 10.1002/jcp.27380. Epub 2018 Oct 26.

DOI:10.1002/jcp.27380
PMID:30362500
Abstract

Cancer is one of the common lifestyle diseases and is considered to be the leading cause of death worldwide. Epstein-Barr virus (EBV)-infected individuals remain asymptomatic; but under certain stress conditions, EBV may lead to the development of cancers such as Burkitt's and Hodgkin's lymphoma and nasopharyngeal carcinoma. EBV-associated cancers result in a large number of deaths in Asian and African population, and no effective cure has still been developed. We, therefore, tried to devise a subunit vaccine with the help of immunoinformatic approaches that can be used for the prevention of EBV-associated malignancies. The epitopes were predicted through B-cell, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) from the different oncogenic proteins of EBV. A vaccine was designed by combining the B-cell and T-cell (HTL and CTL) epitopes through linkers, and for the enhancement of immunogenicity, an adjuvant was added at the N-terminal. Further, homology modeling was performed to generate the 3D structure of the designed vaccine. Moreover, molecular docking was performed between the designed vaccine and immune receptor (TLR-3) to determine the interaction between the final vaccine construct and the immune receptor complex. In addition, molecular dynamics was performed to analyze the stable interactions between the ligand final vaccine model and receptor TLR-3 molecule. Lastly, to check the expression of our vaccine construct, we performed in silico cloning. This study needed experimental validation to ensure its effectiveness and potency to control malignancy.

摘要

癌症是一种常见的生活方式疾病,被认为是全球主要的死亡原因。感染 Epstein-Barr 病毒 (EBV) 的个体无症状;但在某些应激条件下,EBV 可能导致伯基特淋巴瘤和霍奇金淋巴瘤和鼻咽癌等癌症的发展。EBV 相关癌症导致亚洲和非洲人口大量死亡,目前仍未开发出有效的治疗方法。因此,我们试图通过免疫信息学方法设计一种亚单位疫苗,用于预防 EBV 相关恶性肿瘤。通过 EBV 的不同致癌蛋白的 B 细胞、细胞毒性 T 淋巴细胞 (CTL) 和辅助 T 淋巴细胞 (HTL) 预测表位。通过接头将 B 细胞和 T 细胞 (HTL 和 CTL) 表位结合在一起设计疫苗,并在 N 端添加佐剂以增强免疫原性。此外,还进行了同源建模以生成设计疫苗的 3D 结构。此外,还进行了分子对接,以确定设计疫苗与免疫受体 (TLR-3) 之间的相互作用,以确定最终疫苗构建体与免疫受体复合物之间的相互作用。此外,还进行了分子动力学分析,以分析配体最终疫苗模型与受体 TLR-3 分子之间的稳定相互作用。最后,为了检查我们疫苗构建体的表达,我们进行了计算机克隆。这项研究需要进行实验验证,以确保其控制恶性肿瘤的有效性和效力。

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