Zhang Yumin, Zhao Guoqing, Xiong Yangjing, Li Feiyu, Chen Yifan, Cheng Yuqiang, Ma Jingjiao, Wang Henan, Yan Yaxian, Wang Zhaofei, Sun Jianhe
Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 201100, China.
Vet Sci. 2023 May 31;10(6):383. doi: 10.3390/vetsci10060383.
is a significant zoonotic pathogen that is a great threat not only to the swine industry but also to human health, causing arthritis, meningitis, and even streptococcal toxic shock-like syndrome. Owing to its many serotypes and high geographic variability, an efficacious cross-protective vaccine is not readily available. Therefore, this study aimed to design a universal multi-epitope vaccine (MVHP6) that involved three highly immunogenic proteins of , namely, the surface antigen containing a glycosaminoglycan binding domain (HP0197), endopeptidase (PepO), and 6-phosphogluconate dehydrogenase (6PGD). Forecasted T-cell and B-cell epitopes with high antigenic properties and a suitable adjuvant were linked to construct a multi-epitope vaccine. In silico analysis showed that the selected epitopes were conserved in highly susceptible serotypes for humans. Thereafter, we evaluated the different parameters of MVHP6 and showed that MVHP6 was highly antigenic, non-toxic, and non-allergenic. To verify whether the vaccine could display appropriate epitopes and maintain high stability, the MVHP6 tertiary structure was modeled, refined, and validated. Molecular docking studies revealed a strong binding interaction between the vaccine and the toll-like receptor (TLR4), whereas molecular dynamics simulations demonstrated the vaccine's compatibility, binding stability, and structural compactness. Moreover, the in silico analysis showed that MVHP6 could evoke strong immune responses and enable worldwide population coverage. Moreover, MVHP6 was cloned into the pET28a (+) vector in silico to ensure the credibility, validation, and proper expression of the vaccine construct. The findings suggested that the proposed multi-epitope vaccine can provide cross-protection against infections.
是一种重要的人畜共患病原体，不仅对养猪业构成巨大威胁，也对人类健康构成威胁，可导致关节炎、脑膜炎，甚至链球菌中毒性休克样综合征。由于其众多血清型和高度的地理变异性，目前尚无有效的交叉保护疫苗。因此，本研究旨在设计一种通用的多表位疫苗（MVHP6），该疫苗涉及的三种高度免疫原性蛋白，即含有糖胺聚糖结合域的表面抗原（HP0197）、内肽酶（PepO）和6-磷酸葡萄糖酸脱氢酶（6PGD）。将预测的具有高抗原特性的T细胞和B细胞表位与合适的佐剂连接，构建多表位疫苗。计算机模拟分析表明，所选表位在人类高度易感血清型中具有保守性。此后，我们评估了MVHP6的不同参数，结果表明MVHP6具有高抗原性、无毒性和无过敏性。为了验证该疫苗是否能展示合适的表位并保持高稳定性，对MVHP6的三级结构进行了建模、优化和验证。分子对接研究揭示了该疫苗与Toll样受体（TLR4）之间有强烈的结合相互作用，而分子动力学模拟证明了该疫苗的兼容性、结合稳定性和结构紧凑性。此外，计算机模拟分析表明MVHP6能引发强烈的免疫反应并实现全球人群覆盖。此外，在计算机模拟中将MVHP6克隆到pET28a（+）载体中，以确保疫苗构建体的可信度、有效性和正确表达。研究结果表明，所提出的多表位疫苗可以提供针对感染的交叉保护。
