Ramalingam Prasanna Srinivasan, Aranganathan Mahalakshmi, Hussain Md Sadique, Elangovan Sujatha, Chellasamy Gayathri, Balakrishnan Purushothaman, Mekala Janaki Ramaiah, Yun Kyusik, Arumugam Sivakumar
Protein Engineering Lab, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, TamilNadu, India.
School of Natural Sciences and Mathematics, The University of Texas at Dallas, Richardson, TX, United States.
Front Immunol. 2025 May 19;16:1576557. doi: 10.3389/fimmu.2025.1576557. eCollection 2025.
Infectious diseases continue to challenge human health with high incidence and mortality rates worldwide. Notably, the adaptability of RNA viruses, highlighted by outbreaks of SARS, MERS, and COVID-19, emphasizes the timely need for effective therapeutics. Saint Louis encephalitis virus (SLEV) belonging to the Flaviviridae family is an RNA virus that mostly affects the central nervous system (CNS) of humans. Although supportive care treatments such as antiemetics and painkillers are being used against SLEV infection, it still lacks potential therapeutics for the effective treatment.
Reverse vaccinology and immunoinformatics approaches help in the identification of suitable epitopes to design a vaccine construct that will activate both B- and T-cell-mediated responses. Previous studies used only the envelope protein E for the vaccine design, but we have used multiple protein targets to enhance the vaccine efficacy. Thus, in the present study, we have designed a multi-epitope subunit vaccine that specifically targets the membrane glycoprotein M, envelope protein E, and anchored capsid protein anchC of SLEV.
Our results indicated that the vaccine construct is structurally stable, antigenic, non-allergic, non-toxic, and soluble. Additionally, the vaccine construct was structurally refined and indicated significant binding affinity toward the Toll-like receptor 4 (TLR-4) supported by molecular docking and molecular dynamics simulations. Furthermore, it also indicated that it has the potential to induce an immune response.
In addition, it has been cloned in the pET-28a (+) vector-6xHis-TEV-ORF9c expression vector for further experimental validation. We also recommend to evaluate the designed vaccine's therapeutic efficacy through and studies in the near future.
传染病在全球范围内持续以高发病率和死亡率威胁人类健康。值得注意的是,SARS、MERS和COVID - 19疫情凸显了RNA病毒的适应性,这强调了及时开发有效治疗方法的必要性。圣路易斯脑炎病毒(SLEV)属于黄病毒科,是一种主要影响人类中枢神经系统(CNS)的RNA病毒。尽管目前使用止吐药和止痛药等支持性护理治疗SLEV感染,但仍缺乏有效的潜在治疗方法。
反向疫苗学和免疫信息学方法有助于识别合适的表位,以设计能够激活B细胞和T细胞介导反应的疫苗构建体。以往研究仅使用包膜蛋白E进行疫苗设计,但我们使用了多个蛋白靶点来提高疫苗效力。因此,在本研究中,我们设计了一种多表位亚单位疫苗,专门针对SLEV的膜糖蛋白M、包膜蛋白E和锚定衣壳蛋白anchC。
我们的结果表明,该疫苗构建体结构稳定、具有抗原性、无过敏反应、无毒且可溶。此外,通过分子对接和分子动力学模拟支持,该疫苗构建体在结构上得到优化,并显示出对Toll样受体4(TLR - 4)具有显著的结合亲和力。此外,还表明它具有诱导免疫反应的潜力。
此外,它已被克隆到pET - 28a(+)载体 - 6xHis - TEV - ORF9c表达载体中,用于进一步的实验验证。我们还建议在不久的将来通过[具体研究方法1]和[具体研究方法2]研究来评估所设计疫苗的治疗效果。