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基于免疫信息学方法设计宫颈癌多表位疫苗

Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches.

机构信息

Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

Sci Rep. 2021 Jun 11;11(1):12397. doi: 10.1038/s41598-021-91997-4.

Abstract

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

摘要

宫颈癌是由人乳头瘤病毒(HPV)引起的,是全球女性中第四常见的癌症类型。虽然有预防性 HPV 疫苗,但它们没有治疗作用,也不能清除现有的感染。本研究旨在使用反向疫苗学设计一种治疗宫颈癌的疫苗。在这项研究中,选择 HPV16 的 E6 和 E7 癌蛋白作为表位预测的靶抗原。预测了细胞毒性 T 淋巴细胞(CTL)和辅助性 T 淋巴细胞(HTL)表位,并根据抗原性、变应原性和毒性选择最佳表位。最终的疫苗构建体由选定的表位以及适当的佐剂和接头组成。多表位疫苗在理化性质、抗原性和变应原性方面进行了评估。预测了疫苗构建体的三级结构。此外,还进行了一些分析,包括分子对接、分子动力学(MD)模拟和疫苗构建体的计算机克隆。结果表明,最终提出的疫苗可被视为 HPV 的有效治疗性疫苗;然而,需要进行体外和体内实验来验证该疫苗候选物的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7d/8196015/e3e4780aff4e/41598_2021_91997_Fig1_HTML.jpg

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