Alnuqaydan Abdullah M, Eisa Alaa Abdulaziz
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia.
Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Meddina 30002, Saudi Arabia.
Biology (Basel). 2024 Sep 20;13(9):738. doi: 10.3390/biology13090738.
Omsk Hemorrhagic Fever Virus (OHFV) is an RNA virus with a single-stranded, positive-sense genome. It is classified under the Flaviviridae family. The genome of this virus is 98% similar to the Alkhurma hemorrhagic fever virus (AHFV), which belongs to the same family. Cases of the virus have been reported in various regions of Saudi Arabia. Both OHFV and AHFV have similarities in pathogenic polyprotein targets. No effective and licensed vaccines are available to manage OHFV infections. Therefore, an effective and safe vaccine is required that can activate protective immunity against OHFV. The current study aimed to design a multiepitope subunit vaccine against the OHFV utilizing several immunoinformatic tools. The polyprotein of OHFV was selected and potent antigenic, non-allergenic, and nontoxic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes were chosen. After screening, eight (8) CTL, five (5) HTL, and six (6) B cell epitopes were joined with each other using different linkers. Adjuvant human beta defensin-2 was also linked to the epitopes to increase vaccine antigenic and immunogenic efficiency. The designed vaccine was docked with Toll-like receptor 4 (TLR4) as it activates and induces primary and secondary immune responses against OHFV. Codon optimization was carried out, which resulted in a CAI value of 0.99 and 53.4% GC contents. In addition, the construct was blindly docked to the TLR4 immune receptor and subjected to conformational dynamics simulation analysis to interpret the intricate affinity and comprehend the time-dependent behavior. Moreover, it was predicted that immune responses to the developed vaccine construct reported formation of strong humoral and cellular immune cells. Therefore, the proposed vaccine may be considered in experimental assays to combat OHFV infections. Laboratory experiments for the above predictions are essential in order to evaluate the effectiveness, safety, and protective properties of the subject in question.
鄂木斯克出血热病毒(OHFV)是一种具有单链正 sense 基因组的RNA病毒。它被归类于黄病毒科。该病毒的基因组与同属一科的阿尔胡尔马出血热病毒(AHFV)有98%的相似性。沙特阿拉伯的各个地区都报告过该病毒的病例。OHFV和AHFV在致病多聚蛋白靶点上有相似之处。目前尚无有效的许可疫苗来控制OHFV感染。因此,需要一种能激活针对OHFV的保护性免疫的有效且安全的疫苗。当前的研究旨在利用多种免疫信息学工具设计一种针对OHFV的多表位亚单位疫苗。选择了OHFV的多聚蛋白,并挑选了强效的抗原性、非致敏性和无毒的细胞毒性T淋巴细胞(CTL)、辅助性T淋巴细胞(HTL)和线性B淋巴细胞(LBL)表位。筛选后,使用不同的连接子将8个CTL、5个HTL和6个B细胞表位相互连接。佐剂人β-防御素-2也与这些表位相连,以提高疫苗的抗原性和免疫原性效率。设计的疫苗与Toll样受体4(TLR4)进行对接,因为它能激活并诱导针对OHFV的初级和次级免疫反应。进行了密码子优化,结果密码子适应指数(CAI)值为0.99,GC含量为53.4%。此外,将构建体盲目对接至TLR4免疫受体,并进行构象动力学模拟分析,以解释复杂的亲和力并理解时间依赖性行为。此外,预测针对所开发疫苗构建体的免疫反应会形成强大的体液免疫和细胞免疫细胞。因此,在对抗OHFV感染的实验测定中可考虑使用所提议的疫苗。为了评估相关对象的有效性、安全性和保护特性,对上述预测进行实验室实验至关重要。