College of Biology, Hunan University, Changsha 410082, China.
Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
Int J Mol Sci. 2024 Aug 13;25(16):8828. doi: 10.3390/ijms25168828.
Transmissible gastroenteritis virus (TGEV) is an etiological agent of enteric disease that results in high mortality rates in piglets. The economic impact of the virus is considerable, causing significant losses to the pig industry. The development of an efficacious subunit vaccine to provide promising protection against TGEV is of the utmost importance. The viral antigen, spike glycoprotein (S), is widely regarded as one of the most effective antigenic components for vaccine research. In this study, we employed immunoinformatics and molecular dynamics approaches to develop an 'ideal' multi-epitope vaccine. Firstly, the dominant, non-toxic, highly antigenic T (Th, CTL) and B cell epitopes predicted from the TGEV S protein were artificially engineered in tandem to design candidate subunit vaccines. Molecular docking and dynamic simulation results demonstrate that it exhibits robust interactions with toll-like receptor 4 (TLR4). Of particular significance was the finding that the vaccine was capable of triggering an immune response in mammals, as evidenced by the immune simulation results. The humoral aspect is typified by elevated levels of IgG and IgM, whereas the cellular immune aspect is capable of eliciting the robust production of interleukins and cytokines (IFN-γ and IL-2). Furthermore, the adoption of expression systems for the preparation of vaccines will also result in cost savings. This study offers logical guidelines for the development of a secure and efficacious subunit vaccine against TGEV, in addition to providing a novel theoretical foundation and strategy to prevent associated CoV infections.
传染性胃肠炎病毒(TGEV)是一种引起仔猪高死亡率的肠道疾病病原体。该病毒的经济影响相当大,给养猪业造成了重大损失。开发有效的亚单位疫苗为 TGEV 提供有希望的保护至关重要。病毒抗原,刺突糖蛋白(S),被广泛认为是疫苗研究中最有效的抗原性成分之一。在这项研究中,我们采用免疫信息学和分子动力学方法来开发一种“理想”的多表位疫苗。首先,从 TGEV S 蛋白中预测的优势、无毒、高度抗原性的 T(Th、CTL)和 B 细胞表位被人工串联设计成候选亚单位疫苗。分子对接和动态模拟结果表明,它与 Toll 样受体 4(TLR4)表现出强大的相互作用。特别重要的是,疫苗能够在哺乳动物中引发免疫反应,免疫模拟结果证明了这一点。体液免疫方面表现为 IgG 和 IgM 水平升高,而细胞免疫方面能够引发白细胞介素和细胞因子(IFN-γ 和 IL-2)的强烈产生。此外,采用表达系统制备疫苗也将节省成本。本研究为开发针对 TGEV 的安全有效的亚单位疫苗提供了合理的指导方针,并为预防相关 CoV 感染提供了新的理论基础和策略。