3 Biotech ( IF 2.8 ) Pub Date : 2021-01-11 , DOI: 10.1007/s13205-020-02574-x Ratnadeep Saha 1 , Pratik Ghosh 2 , V L S Prasad Burra 3
COVID-19 caused by SARS-CoV-2 was declared a global pandemic by WHO (World Health Organization) in March, 2020. Within 6 months, nearly 750,000 deaths are claimed by COVID-19 across the globe. This called for immediate social, scientific, technological, public and community interventions. Considering the severity of infection and the associated mortalities, global efforts are underway to develop preventive measures against SARS-CoV-2. Among the SARS-CoV-2 target proteins, Spike (S) glycoprotein (a.k.a S Protein) is the most studied target known to trigger strong host immune response. A detailed analysis of S protein-based epitopes enabled us to design a novel B-cell-derived T-cell Multi-epitope-based peptide (MEBP) vaccine candidate. This involved a systematic and comprehensive computational protocol consisting of prediction of dual-purpose epitopes and designing an MEBP vaccine construct. This was followed by 3D structure validation, MEBP complex interaction studies, in silico cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The dual-purpose epitope prediction protocol was designed such that the same epitope elicits both humoral and cellular immune response unlike the earlier designs. Further, the epitopes predicted were screened against stringent criteria to ensure selection of a potent candidate with maximum antigen coverage and best immune response. The vaccine dose-based immune response simulation studies revealed a rapid antigen clearance through antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis strongly indicate that the vaccine construct is indeed a potent vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.
中文翻译:
使用计算方法设计针对 SARS-CoV-2 的下一代基于多表位的肽疫苗候选者
由 SARS-CoV-2 引起的 COVID-19 于 2020 年 3 月被 WHO(世界卫生组织)宣布为全球大流行病。在 6 个月内,全球有近 750,000 人死于 COVID-19。这需要立即进行社会、科学、技术、公共和社区干预。考虑到感染的严重性和相关的死亡率,全球正在努力制定针对 SARS-CoV-2 的预防措施。在 SARS-CoV-2 靶蛋白中,Spike (S) 糖蛋白(又名 S 蛋白)是已知的引发强烈宿主免疫反应的研究最多的靶点。基于 S 蛋白的表位的详细分析使我们能够设计一种新的 B 细胞衍生的 T 细胞多表位肽 (MEBP) 候选疫苗。这涉及系统和全面的计算协议,包括预测双重用途表位和设计 MEBP 疫苗构建体。随后是 3D 结构验证、MEBP 复合物相互作用研究、计算机克隆和基于疫苗剂量的免疫反应模拟,以评估疫苗构建体的免疫原性效力。双重目的表位预测方案的设计使得相同的表位同时引发体液和细胞免疫反应,这与早期的设计不同。此外,根据严格的标准筛选预测的表位,以确保选择具有最大抗原覆盖率和最佳免疫反应的有效候选者。基于疫苗剂量的免疫反应模拟研究表明,在反复接触疫苗期间,通过抗体产生和细胞介导的免疫水平升高,可以快速清除抗原。分析的有利结果有力地表明,疫苗构建体确实是一种有效的候选疫苗,并准备好进行下一步的实验验证和功效研究。