Shah Syed Zawar, Jabbar Basit, Mirza Muhammad Usman, Waqas Muhammad, Aziz Shahkaar, Halim Sobia Ahsan, Ali Amjad, Rafique Shazia, Idrees Muhammad, Khalid Asaad, Abdalla Ashraf N, Khan Ajmal, Al-Harrasi Ahmed
Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan.
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada.
Vaccines (Basel). 2022 Dec 27;11(1):61. doi: 10.3390/vaccines11010061.
Crimean-Congo haemorrhagic fever (CCHF), caused by Crimean-Congo haemorrhagic fever virus (CCHFV), is a disease of worldwide importance (endemic yet not limited to Asia, Middle East, and Africa) and has triggered several outbreaks amounting to a case fatality rate of 10-40% as per the World Health Organization. Genetic diversity and phylogenetic data revealed that the Asia-1 genotype of CCHFV remained dominant in Pakistan, where 688 confirmed cases were reported between the 2012-2022 period. Currently, no approved vaccine is available to tackle the viral infection. Epitope-based vaccine design has gained significant attention in recent years due to its safety, timeliness, and cost efficiency compared to conventional vaccines. In the present study, we employed a robust immunoinformatics-based approach targeting the structural glycoproteins G1 and G2 of CCHFV (Asia-1 genotype) to design a multi-epitope vaccine construct. Five B-cells and six cytotoxic T-lymphocytes (CTL) epitopes were mapped and finalized from G1 and G2 and were fused with suitable linkers (EAAAK, GGGS, AAY, and GPGPG), a PADRE sequence (13 aa), and an adjuvant (50S ribosomal protein L7/L12) to formulate a chimeric vaccine construct. The selected CTL epitopes showed high affinity and stable binding with the binding groove of common human HLA class I molecules (HLA-A02:01 and HLA-B44:02) and mouse major histocompatibility complex class I molecules. The chimeric vaccine was predicted to be an antigenic, non-allergenic, and soluble molecule with a suitable physicochemical profile. Molecular docking and molecular dynamics simulation indicated a stable and energetically favourable interaction between the constructed antigen and Toll-like receptors (TLR2, TLR3, and TLR4). Our results demonstrated that innate, adaptive, and humoral immune responses could be elicited upon administration of such a potent muti-epitope vaccine construct. These results could be helpful for an experimental vaccinologist to develop an effective vaccine against the Asia-1 genotype of CCHFV.
克里米亚-刚果出血热（CCHF）由克里米亚-刚果出血热病毒（CCHFV）引起，是一种具有全球重要性的疾病（流行但不限于亚洲、中东和非洲），据世界卫生组织统计，已引发多次疫情，病死率达10%-40%。遗传多样性和系统发育数据显示，CCHFV的亚洲-1基因型在巴基斯坦仍然占主导地位，2012年至2022年期间该国报告了688例确诊病例。目前，尚无获批的疫苗可用于应对这种病毒感染。近年来，基于表位的疫苗设计因其与传统疫苗相比具有安全性、及时性和成本效益而备受关注。在本研究中，我们采用了一种强大的基于免疫信息学的方法，针对CCHFV（亚洲-1基因型）的结构糖蛋白G1和G2设计了一种多表位疫苗构建体。从G1和G2中筛选并确定了5个B细胞表位和6个细胞毒性T淋巴细胞（CTL）表位，并与合适的接头（EAAAK、GGGS、AAY和GPGPG）、一个PADRE序列（13个氨基酸）和一种佐剂（50S核糖体蛋白L7/L12）融合，以构建一种嵌合疫苗构建体。所选的CTL表位与常见的人类HLA I类分子（HLA-A02:01和HLA-B44:02）以及小鼠主要组织相容性复合体I类分子的结合槽具有高亲和力和稳定的结合。预测该嵌合疫苗是一种具有合适理化特性的抗原性、非致敏性和可溶性分子。分子对接和分子动力学模拟表明，构建的抗原与Toll样受体（TLR2、TLR3和TLR4）之间存在稳定且能量有利的相互作用。我们的结果表明，接种这种有效的多表位疫苗构建体可引发先天性、适应性和体液免疫反应。这些结果可能有助于实验疫苗学家开发一种针对CCHFV亚洲-1基因型的有效疫苗。
