State key laboratories of chemical Resources Engineering Beijing University of chemical technology, Beijing 100029, China.
Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126678. doi: 10.1016/j.ijbiomac.2023.126678. Epub 2023 Sep 2.
Jamestown Canyon virus (JCV) is a deadly viral infection transmitted by various mosquito species. This mosquito-borne virus belongs to Bunyaviridae family, posing a high public health threat in the in tropical regions of the United States causing encephalitis in humans. Common symptoms of JCV include fever, headache, stiff neck, photophobia, nausea, vomiting, and seizures. Despite the availability of resources, there is currently no vaccine or drug available to combat JCV. The purpose of this study was to develop an epitope-based vaccine using immunoinformatics approaches. The vaccine aimed to be secure, efficient, bio-compatible, and capable of stimulating both innate and adaptive immune responses. In this study, the protein sequence of JCV was obtained from the NCBI database. Various bioinformatics methods, including toxicity evaluation, antigenicity testing, conservancy analysis, and allergenicity assessment were utilized to identify the most promising epitopes. Suitable linkers and adjuvant sequences were used in the design of vaccine construct. 50s ribosomal protein sequence was used as an adjuvant at the N-terminus of the construct. A total of 5 CTL, 5 HTL, and 5 linear B cell epitopes were selected based on non-allergenicity, immunological potential, and antigenicity scores to design a highly immunogenic multi-peptide vaccine construct. Strong interactions between the proposed vaccine and human immune receptors, i.e., TLR-2 and TLR-4, were revealed in a docking study using ClusPro software, suggesting their possible relevance in the immunological response to the vaccine. Immunological and physicochemical properties assessment ensured that the proposed vaccine demonstrated high immunogenicity, solubility and thermostability. Molecular dynamics simulations confirmed the strong binding affinities, as well as dynamic and structural stability of the proposed vaccine. Immune simulation suggest that the vaccine has the potential to effectively stimulate cellular and humoral immune responses to combat JCV infection. Experimental and clinical assays are required to validate the results of this study.
贾第虫病毒(JCV)是一种由多种蚊子传播的致命病毒感染。这种蚊媒病毒属于布尼亚病毒科,在美国热带地区对公共健康构成高度威胁,可导致人类脑炎。JCV 的常见症状包括发热、头痛、颈项强直、畏光、恶心、呕吐和癫痫发作。尽管有资源可用,但目前尚无针对 JCV 的疫苗或药物。本研究旨在使用免疫信息学方法开发一种基于表位的疫苗。该疫苗旨在安全、高效、生物兼容,并能刺激先天和适应性免疫反应。在这项研究中,从 NCBI 数据库中获得了 JCV 的蛋白质序列。利用各种生物信息学方法,包括毒性评估、抗原性测试、保守性分析和变应原性评估,来鉴定最有前途的表位。在疫苗构建的设计中使用了合适的接头和佐剂序列。50s 核糖体蛋白序列被用作构建体 N 端的佐剂。根据非变应原性、免疫潜力和抗原性评分,选择了 5 个 CTL、5 个 HTL 和 5 个线性 B 细胞表位,用于设计高免疫原性的多肽疫苗构建体。在使用 ClusPro 软件进行对接研究中,发现所提出的疫苗与人类免疫受体(TLR-2 和 TLR-4)之间存在强烈的相互作用,这表明它们在疫苗免疫反应中可能具有相关性。免疫和物理化学性质评估确保了所提出的疫苗具有高免疫原性、溶解性和热稳定性。分子动力学模拟证实了所提出的疫苗具有很强的结合亲和力,以及动态和结构稳定性。免疫模拟表明,该疫苗有可能有效地刺激细胞和体液免疫反应,以对抗 JCV 感染。需要进行实验和临床检测来验证本研究的结果。