DataSheet_1_Development of a Novel Multi-Epitope Vaccine Against Crimean-Congo Hemorrhagic Fever Virus: An Integrated Reverse Vaccinology, Vaccine Informatics and Biophysics Approach.docx

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and interferon-gamma induction potential. The epitopes were engineered into an MEV through suitable linkers and adjuvating with an appropriate adjuvant molecule. The recombinant vaccine sequence revealed all favorable physicochemical properties allowing the ease of experimental analysis in vivo and in vitro. The vaccine 3D structure was established ab initio. Furthermore, the vaccine displayed excellent binding affinity for critical innate immune receptors: TLR2 (−14.33 kcal/mol) and TLR3 (−6.95 kcal/mol). Vaccine binding with these receptors was dynamically analyzed in terms of complex stability and interaction energetics. Finally, we speculate the vaccine sequence reported here has excellent potential to evoke protective and specific immune responses subject to evaluation of downstream experimental analysis.

克里米亚-刚果出血热（Crimean-Congo hemorrhagic fever, CCHF）是一种由蜱传播的克里米亚-刚果出血热病毒（CCHFV）引发的烈性高致病人畜共患病毒性疾病。该病毒在多个国家呈地方性流行，病死率介于10%至40%之间。由于目前尚无获批上市的疫苗或治疗手段用于克里米亚-刚果出血热的防控，本研究旨在应用现代计算生物学方法，开发一款多表位疫苗（multi-epitope vaccine, MEV），其抗原表位源自CCHFV基因组并经过优先级筛选。整合的计算分析结果显示，从核蛋白（Nucleoprotein, N）、RNA依赖RNA聚合酶（RNA dependent RNA polymerase, RdRp）、糖蛋白N（Glycoprotein N, Gn/G2）以及糖蛋白C（Glycoprotein C, Gc/G1）中共筛选得到9个免疫优势表位。上述表位的覆盖范围可达全球99.74%的人群。该系列表位对B细胞与T细胞参考等位基因集展现出优异的结合亲和力，同时具备高抗原性、非致敏性、良好的可溶性、零毒性以及诱导干扰素-γ产生的潜能。研究人员通过合适的连接肽将这些表位进行拼接，并辅以恰当的佐剂分子构建得到多表位疫苗。该重组疫苗序列具备所有理想的理化特性，可便捷开展体内（in vivo）与体外（in vitro）实验验证。本研究通过从头建模方法解析了该疫苗的三维结构。进一步分析显示，该疫苗可与关键先天免疫受体Toll样受体2（TLR2，结合自由能为-14.33 kcal/mol）与Toll样受体3（TLR3，结合自由能为-6.95 kcal/mol）实现高效结合。研究团队针对该疫苗与受体形成的复合物的稳定性及相互作用能开展了动态结合分析。最后，本研究推测本次报道的疫苗序列具备引发保护性特异性免疫应答的巨大潜力，有待后续实验研究进一步验证。