PDF(Pubmed)
Abstract：
Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.
摘要：
汉坦病毒是属于布尼亚病毒科的单链RNA病毒，在世界范围内引起汉坦病毒心肺综合征（HCPS）和肾综合征出血热（HFRS）。目前,没有有效的疫苗接种或治疗方法可用于治疗汉坦病毒，因此，迫切需要研究以制定该疾病的治疗方法。计算疫苗设计目前是一个高度准确的，设计针对不同疾病的有效疫苗的时间和成本效益方法。在目前的研究中,我们入围了高抗原蛋白，即，信封,和来自汉坦病毒蛋白质组的核蛋白，并经过高抗原表位的选择，设计下一代多表位疫苗构建体。一种高度抗原性和稳定的佐剂与免疫表位（T细胞，B细胞,和HTL)来设计Env-Vac，NP-Vac,和Com-Vac结构，表现出更强的抗原性，非过敏性，和良好的理化性质。此外，预测了3D结构,对接分析揭示了与人Toll样受体3(TLR3)的强相互作用以启动免疫级联反应.为Env-Vac计算的总自由能，NP-Vac,Com-Vac为-50.02千卡/摩尔，-24.13kcal/mol,和-62.30千卡/摩尔，分别。硅克隆，结果表明Env-Vac的CAI值，NP-Vac,和Com-Vac分别为0.957、0.954和0.956，而其相应的GC含量为65.1%，64.0%,和63.6%。此外,三剂量注射的免疫模拟结果释放了显著水平的IgG，IgM,白细胞介素,和细胞因子，以及随着时间的推移抗原清除，在接受疫苗和两次加强剂量后。我们针对汉坦病毒的疫苗被发现具有高度免疫原性，诱导强大的免疫反应，需要临床使用的实验验证。
