Sayed Sifat Bin, Nain Zulkar, Khan Md Shakil Ahmed, Abdulla Faruq, Tasmin Rubaia, Adhikari Utpal Kumar
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, 7003 Bangladesh.
Department of Statistics, Faculty of Sciences, Islamic University, Kushtia, 7003 Bangladesh.
Int J Pept Res Ther. 2020;26(4):2089-2107. doi: 10.1007/s10989-019-10003-8. Epub 2020 Jan 2.
Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N = 8 and N = 6) and B-cell (N = 4) epitopes from each LASV-derived protein in addition with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~ 68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor 2 (TLR2) showed binding efficiency followed by dynamics simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.
拉沙病毒(LASV)可引发一种被称为拉沙热的急性病毒性出血热。由于缺乏针对拉沙病毒的充分治疗和预防措施,其流行地区的死亡率很高。在本研究中,利用免疫信息学设计了一种多表位疫苗作为针对该病毒的预防剂。经过严格评估后,该疫苗采用来自每种拉沙病毒衍生蛋白的T细胞(N = 8和N = 6)和B细胞(N = 4)表位构建而成,并添加了合适的连接子和佐剂。对设计的疫苗(约68 kDa)的物理化学性质、免疫原性效力和安全性进行了评估。此外,我们疫苗所选择的细胞毒性T淋巴细胞(CTL)和辅助性T淋巴细胞(HTL)表位在全球人群中的覆盖率达97.37%。此外,二硫键工程也提高了嵌合疫苗的稳定性。我们的疫苗蛋白与Toll样受体2(TLR2)的分子对接显示出结合效率,随后进行动力学模拟以实现稳定相互作用。此外,免疫模拟和重复暴露模拟分别表明细胞介导免疫水平较高和抗原清除迅速。最后,在计算机克隆中使用了优化密码子,以确保在K12细菌内实现更高表达。通过进一步的体外和体内评估,我们相信我们提出的肽疫苗将是对抗拉沙热的潜在免疫原。