Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran.
Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran.
J Biomed Inform. 2019 May;93:103160. doi: 10.1016/j.jbi.2019.103160. Epub 2019 Mar 27.
Crimean-Congo hemorrhagic fever (CCHF) is considered one of the major public health concerns with case fatality rates of up to 80%. Currently, there is no effective approved vaccine for CCHF. In this study, we used a computer-aided vaccine design approach to develop the first multi-epitope recombinant vaccine for CCHF. For this purpose, linear B-cell and T-cell binding epitopes from two structural glycoproteins of CCHF virus including Gc and Gn were predicted. The epitopes were further studied regarding their antigenicity, allergenicity, hydrophobicity, stability, toxicity and population coverage. A total number of seven epitopes including five T-cell and two B-cell epitopes were screened for the final vaccine construct. Final vaccine construct composed of 382 amino acid residues which were organized in four domains including linear B-cell, T-cell epitopes and cholera toxin B-subunit (CTxB) along with heat labile enterotoxin IIc B subunit (LT-IIc) as adjuvants. All the segments were joined using appropriate linkers. The physicochemical properties as well as the presence of IFN-γ inducing epitopes in the proposed vaccine, was also checked to determining the vaccine stability, solubility and its ability to induce cell-mediated immune responses. The 3D structure of proposed vaccine was subjected to the prediction of computational B-cell epitopes and molecular docking studies with MHC-I and II molecules. Furthermore, molecular dynamics stimulations were performed to study the vaccine-MHCs complexes stability during stimulation time. The results suggest that our proposed vaccine was stable, well soluble in water and potentially antigenic. Results also demonstrated that the vaccine can induce both humoral and cell-mediated immune responses and could serve as a promising anti-CCHF vaccine candidate.
克里米亚-刚果出血热（CCHF）被认为是主要的公共卫生关注之一，其病死率高达 80%。目前，尚无针对 CCHF 的有效批准疫苗。在这项研究中，我们使用计算机辅助疫苗设计方法开发了首个针对 CCHF 的多表位重组疫苗。为此，预测了 CCHF 病毒的两种结构糖蛋白 Gc 和 Gn 中的线性 B 细胞和 T 细胞结合表位。进一步研究了这些表位的抗原性、过敏性、疏水性、稳定性、毒性和人群覆盖率。总共筛选了七个表位，包括五个 T 细胞表位和两个 B 细胞表位，用于最终的疫苗构建。最终的疫苗构建由 382 个氨基酸残基组成，分为四个结构域，包括线性 B 细胞表位、T 细胞表位和霍乱毒素 B 亚单位（CTxB）以及不耐热肠毒素 IIc B 亚单位（LT-IIc）作为佐剂。所有片段均使用合适的接头连接。还检查了提议疫苗的物理化学性质以及 IFN-γ 诱导表位的存在，以确定疫苗的稳定性、溶解度及其诱导细胞介导免疫反应的能力。提议疫苗的 3D 结构还进行了计算 B 细胞表位的预测和与 MHC-I 和 II 分子的分子对接研究。此外，还进行了分子动力学模拟，以研究在刺激时间内疫苗-MHC 复合物的稳定性。结果表明，我们提出的疫苗稳定、水溶性好且具有潜在的抗原性。结果还表明，该疫苗可诱导体液和细胞介导的免疫反应，并可能成为有前途的抗 CCHF 疫苗候选物。
