Exploring Proteome of Crimean-Congo Hemorrhagic Fever Virus to Construct Multiepitope Based Subunit Vaccine: Molecular Docking with Immunoinformatic Framework

Hira Shafique, Iqra Shafique, Farah Shahid, Nimra Asif, Usman Ali Ashfaq Ashfaq
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 Methodology: The study contains immunoinformatic and docking methodologies to obtain a MESV by choosing highly antigenic and overlapping epitopes comprising of 8 epitopes of both MHC class I and II from viral proteins. Epitopes were chosen which were conserved within the epitopes of IFN- gamma, T-cell and B-cell. Then these epitopes were joined to final peptide by GPGPG and AAY linkers. An adjuvant was added at N terminal of vaccine via EAAAK linker for the improvement of vaccine’s immunogenicity.
 Findings: Our final construct was comprised of 278 amino acids. To validate the vaccine’s immunogenicity and safety, its physiochemical properties, allergenicity as well as antigenicity were checked and it was predicted to be non-allergenic and antigenic. The construct was further analyzed by molecular docking within vaccine and TLR3 receptor to assure its molecular interaction and binding affinity. In the end, In-silico cloning was also carried out for ensuring its expression efficiency.
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Abstract

Purpose: Crimean-Congo hemorrhagic fever virus (CCHFV), a single-stranded RNA (ssRNA) virus that spreads via tick bites. For the treatment of CCHFV, there is still a lack of vaccine or any antiviral medicine. For this purpose, a study was performed to design a multiepitope based subunit vaccine (MESV) for effective prevention against CCHFV infection. Methodology: The study contains immunoinformatic and docking methodologies to obtain a MESV by choosing highly antigenic and overlapping epitopes comprising of 8 epitopes of both MHC class I and II from viral proteins. Epitopes were chosen which were conserved within the epitopes of IFN- gamma, T-cell and B-cell. Then these epitopes were joined to final peptide by GPGPG and AAY linkers. An adjuvant was added at N terminal of vaccine via EAAAK linker for the improvement of vaccine’s immunogenicity. Findings: Our final construct was comprised of 278 amino acids. To validate the vaccine’s immunogenicity and safety, its physiochemical properties, allergenicity as well as antigenicity were checked and it was predicted to be non-allergenic and antigenic. The construct was further analyzed by molecular docking within vaccine and TLR3 receptor to assure its molecular interaction and binding affinity. In the end, In-silico cloning was also carried out for ensuring its expression efficiency. Recommendations: Nonetheless, the designed construct is proposed to be tested in laboratory settings to confirm its immunogenicity and safety.
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探索克里米亚-刚果出血热病毒蛋白质组构建基于多表位的亚单位疫苗:与免疫信息学框架的分子对接
目的:克里米亚-刚果出血热病毒(CCHFV),一种单链RNA (ssRNA)病毒,通过蜱叮咬传播。对于治疗CCHFV,仍然缺乏疫苗或任何抗病毒药物。为此,开展了一项研究,设计一种基于多表位的亚单位疫苗(MESV),以有效预防CCHFV感染。方法:本研究采用免疫信息学和对接方法,通过从病毒蛋白中选择由MHC I类和II类8个表位组成的高抗原性和重叠的表位来获得MESV。选择在IFN- γ、t细胞和b细胞表位内保守的表位。然后这些表位通过GPGPG和AAY连接体与最终肽连接。通过EAAAK连接体在疫苗的N端加入佐剂,提高疫苗的免疫原性。 结果:我们的最终构建由278个氨基酸组成。为验证该疫苗的免疫原性和安全性,对其理化性质、致敏性和抗原性进行了检测,预测其无致敏性和抗原性。通过在疫苗和TLR3受体内的分子对接,进一步分析了该构建体的分子相互作用和结合亲和力。最后,为了保证其表达效率,还进行了In- silicon克隆。 建议:尽管如此,建议在实验室环境中对设计的结构进行测试,以确认其免疫原性和安全性。
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