Shahrear Sazzad, Islam Abul Bashar Mir Md Khademul
Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
Comput Biol Med. 2022 Jan;140:105098. doi: 10.1016/j.compbiomed.2021.105098. Epub 2021 Dec 2.
The Crimean-Congo hemorrhagic fever virus (CCHFV) is a lethal human pathogen belonging to the Nairoviridae family that causes Crimean-Congo hemorrhagic fever (CCHF), a tick-borne infection with an alarming mortality rate of up to 80%. CCHFV is the most widespread tick-borne virus with the potential to trigger a pandemic. To date, no vaccines or therapeutics for CCHF have been authorized. In this study, we implemented immunoinformatics approach for developing CCHF_GN728, a universal mRNA-based multi-epitope vaccine against CCHFV. Glycoprotein precursor (GPC) and nucleoprotein (NP) from the virus were selected and screened for potential immunogenic T- and B-cell epitopes. Our developed antigen exhibited the potential to generate 99.95% population coverage worldwide. Stable epitope-allele interaction was confirmed using molecular docking and dynamics simulation. In silico immune simulation corroborated immune cell response to antigen clearance rate. Optimized codons ensured efficient expression of the mRNA in the host cell. The vaccine exhibited stable and strong interactions with the Toll-like receptors. Our findings suggest that the CCHF_GN728 vaccine will trigger specific anti-CCHFV immune responses. Our model is ready for wet-lab experimentation to assess the efficacy of this putative vaccine candidate.
克里米亚-刚果出血热病毒（CCHFV）是一种致命的人类病原体，属于内罗病毒科，可引起克里米亚-刚果出血热（CCHF），这是一种由蜱传播的感染病，死亡率高达80%，令人震惊。CCHFV是分布最广的蜱传病毒，有可能引发大流行。迄今为止，尚无针对CCHF的疫苗或治疗方法获得批准。在本研究中，我们采用免疫信息学方法开发了CCHF_GN728，这是一种基于mRNA的针对CCHFV的通用多表位疫苗。从该病毒中选择糖蛋白前体（GPC）和核蛋白（NP），并筛选潜在的免疫原性T细胞和B细胞表位。我们开发的抗原在全球范围内显示出能覆盖99.95%人群的潜力。通过分子对接和动力学模拟证实了稳定的表位-等位基因相互作用。计算机免疫模拟证实了免疫细胞对抗原清除率的反应。优化的密码子确保了mRNA在宿主细胞中的有效表达。该疫苗与Toll样受体表现出稳定而强烈的相互作用。我们的研究结果表明，CCHF_GN728疫苗将引发特异性的抗CCHFV免疫反应。我们的模型已准备好进行湿实验室实验，以评估这种假定疫苗候选物的疗效。
