Experimental Medicine Centre, Venezuelan Institute for Scientific Research, Caracas 1020-A, Venezuela.
J Immunol Methods. 2022 Mar;502:113216. doi: 10.1016/j.jim.2022.113216. Epub 2022 Jan 7.
Coronavirus Disease 2019 (COVID-19) represents a new global threat demanding a multidisciplinary effort to fight its etiological agent-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this regard, immunoinformatics may aid to predict prominent immunogenic regions from critical SARS-CoV-2 structural proteins, such as the spike (S) glycoprotein, for their use in prophylactic or therapeutic interventions against this highly pathogenic betacoronavirus. Accordingly, in this study, an integrated immunoinformatics approach was applied to identify cytotoxic T cell (CTC), T helper cell (THC), and Linear B cell (BC) epitopes from the S glycoprotein in an attempt to design a high-quality multi-epitope vaccine. The best CTC, THC, and BC epitopes showed high viral antigenicity and lack of allergenic or toxic residues, as well as CTC and THC epitopes showed suitable interactions with HLA class I (HLA-I) and HLA class II (HLA-II) molecules, respectively. Remarkably, SARS-CoV-2 receptor-binding domain (RBD) and its receptor-binding motif (RBM) harbour several potential epitopes. The structure prediction, refinement, and validation data indicate that the multi-epitope vaccine has an appropriate conformation and stability. Four conformational epitopes and an efficient binding between Toll-like receptor 4 (TLR4) and the vaccine model were observed. Importantly, the population coverage analysis showed that the multi-epitope vaccine could be used globally. Notably, computer-based simulations suggest that the vaccine model has a robust potential to evoke and maximize both immune effector responses and immunological memory to SARS-CoV-2. Further research is needed to accomplish with the mandatory international guidelines for human vaccine formulations.
新型冠状病毒病(COVID-19)是一种新的全球威胁,需要多学科努力来对抗其病原体——严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)。在这方面,免疫信息学可以帮助预测 SARS-CoV-2 关键结构蛋白(如刺突[Spike]糖蛋白)中的主要免疫原性区域,以便将其用于针对这种高致病性β冠状病毒的预防或治疗干预。因此,在这项研究中,应用了一种集成的免疫信息学方法来鉴定 S 糖蛋白中的细胞毒性 T 细胞(CTL)、辅助性 T 细胞(TH)和线性 B 细胞(BC)表位,以期设计一种高质量的多表位疫苗。最佳的 CTL、TH 和 BC 表位具有高病毒抗原性,且缺乏变应原或毒性残基,CTL 和 TH 表位分别与 HLA Ⅰ类(HLA-I)和 HLA Ⅱ类(HLA-II)分子具有合适的相互作用。值得注意的是,SARS-CoV-2 受体结合域(RBD)及其受体结合基序(RBM)包含多个潜在的表位。结构预测、细化和验证数据表明,该多表位疫苗具有适当的构象和稳定性。观察到四个构象表位和 Toll 样受体 4(TLR4)与疫苗模型之间的有效结合。重要的是,人群覆盖率分析表明,该多表位疫苗可在全球范围内使用。值得注意的是,基于计算机的模拟表明,该疫苗模型具有强大的潜力,可以引发并最大限度地增强针对 SARS-CoV-2 的免疫效应反应和免疫记忆。需要进一步的研究来完成人类疫苗制剂的强制性国际准则。