Department of Human Anatomy, Faculty of Basic Medical Science, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria.
Department of Clinical Medicine, Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Aarhus University, Aarhus, Denmark.
Sci Rep. 2022 May 24;12(1):8736. doi: 10.1038/s41598-022-12651-1.
Crimean Congo Hemorrhagic Fever virus (CCHFV) is a deadly human pathogen that causes an emerging zoonotic disease with a broad geographic spread, especially in Africa, Asia, and Europe, and the second most common viral hemorrhagic fever and widely transmitted tick-borne viral disease. Following infection, the patients are presented with a variety of clinical manifestations and a fatality rate of 40%. Despite the high fatality rate, there are unmet clinical interventions, as no antiviral drugs or vaccines for CCHF have been approved. Immunoinformatics pipeline and reverse vaccinology were used in this study to design a multi-epitope vaccine that may elicit a protective humoral and cellular immune response against Crimean-Congo hemorrhagic fever virus infection. Three essential virulent and antigenic proteins (S, M, and L) were used to predict seven CTL and 18 HTL epitopes that were non-allergenic, antigenic, IFN-γ inducing, and non-toxic. The epitopes were connected using linkers and 50S ribosomal protein L7/L12 was used as an adjuvant and raised a multi-epitope vaccine (MEV) that is 567 amino acids long. Molecular docking and simulation of the predicted 3D structure of the MEV with the toll-like (TLR2, TLR3, and TLR4) receptors and major histocompatibility complex (MCH-I and MCH-II) indicate high interactions and stability of the complexes, MM-GBSA free binding energy calculation revealed a favourable protein-protein complex. Maximum MEV expression was achieved with a CAI value of 0.98 through in silico cloning in the Drosophila melanogaster host. According to the immune simulation, IgG1, T-helper cells, T-cytotoxic cells, INF-γ, and IL-2 were predicted to be significantly elevated. These robust computational analyses demonstrated that the proposed MEV is effective in preventing CCHFV infections. However, it is still necessary to conduct both in vitro and in vivo experiments to validate the potential of the vaccine.
克里米亚-刚果出血热病毒（CCHFV）是一种致命的人类病原体，可引起广泛传播的新兴人畜共患病，尤其在非洲、亚洲和欧洲，它是第二种最常见的病毒性出血热和广泛传播的蜱传病毒性疾病。感染后，患者表现出多种临床表现，死亡率为 40%。尽管死亡率很高，但仍缺乏临床干预措施，因为尚无针对克里米亚-刚果出血热的抗病毒药物或疫苗获得批准。本研究采用免疫信息学管道和反向疫苗学设计了一种多表位疫苗，该疫苗可能针对克里米亚-刚果出血热病毒感染引发保护性体液和细胞免疫反应。使用三种必需的毒力和抗原性蛋白（S、M 和 L）来预测七种 CTL 和 18 种 HTL 表位，这些表位是非变应原性、抗原性、IFN-γ诱导性和无毒的。使用接头连接表位，并使用 50S 核糖体蛋白 L7/L12 作为佐剂，构建了一个 567 个氨基酸长的多表位疫苗（MEV）。对 MEV 的预测三维结构与 Toll 样（TLR2、TLR3 和 TLR4）受体和主要组织相容性复合物（MCH-I 和 MCH-II）的分子对接和模拟表明，这些复合物具有高度的相互作用和稳定性，MM-GBSA 自由结合能计算显示出有利的蛋白-蛋白复合物。通过在果蝇宿主中的计算机克隆，实现了最大 MEV 表达，CAI 值为 0.98。根据免疫模拟，IgG1、T 辅助细胞、T 细胞毒性细胞、INF-γ和 IL-2 预计会显著升高。这些强大的计算分析表明，所提出的 MEV 可有效预防 CCHFV 感染。然而，仍有必要进行体外和体内实验来验证该疫苗的潜力。
