Department of Biotechnology, School of Bio and Chemical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamil Nadu, India.
College of Pharmacy, University of Georgia, Athens, GA, USA.
Infect Genet Evol. 2021 Apr;89:104712. doi: 10.1016/j.meegid.2021.104712. Epub 2021 Jan 7.
An immunoinformatics-based approach was used to identify potential multivalent subunit CTL vaccine candidates for SARS-CoV-2. Criteria for computational screening included antigen processing, antigenicity, allergenicity, and toxicity. A total of 2604 epitopes were found to be strong binders to MHC class I molecules when analyzed using IEDB tools. Further testing for antigen processing yielded 826 peptides of which 451 were 9-mers that were analyzed for potential antigenicity. Antigenic properties were predicted for 102 of the 451 peptides. Further assessment for potential allergenicity and toxicity narrowed the number of candidate CTL epitopes to 50 peptide sequences, 45 of which were present in all strains of SARS-CoV-2 that were tested. The predicted CTL epitopes were then tested to eliminate those with MHC class II binding potential, a property that could induce hyperinflammatory responses mediated by T2 cells in immunized hosts. Eighteen of the 50 epitopes did not show class II binding potential. To our knowledge this is the first comprehensive analysis on the proteome of SARS-CoV-2 for prediction of CTL epitopes lacking binding properties that could stimulate unwanted T2 responses. Future studies will be needed to assess these epitopes as multivalent subunit vaccine candidates which stimulate protective CTL responses against SARS-COV-2.
我们采用免疫信息学方法鉴定了针对 SARS-CoV-2 的潜在多价亚单位 CTL 疫苗候选物。计算筛选的标准包括抗原加工、抗原性、变应原性和毒性。使用 IEDB 工具分析后，共发现 2604 个表位与 MHC Ⅰ类分子具有强结合能力。进一步进行抗原加工检测，得到了 826 个肽段，其中 451 个是 9 聚体肽段，用于分析潜在的抗原性。对 102 个 451 个肽段进行了抗原性预测。进一步评估潜在的变应原性和毒性，将候选 CTL 表位的数量缩小到 50 个肽序列，其中 45 个存在于所有测试的 SARS-CoV-2 株中。然后对预测的 CTL 表位进行测试，以消除与 MHC Ⅱ类结合潜力的表位，这种特性可能会在免疫宿主中诱导由 T2 细胞介导的过度炎症反应。在这 50 个表位中，有 18 个没有显示出 II 类结合潜力。据我们所知，这是首次针对 SARS-CoV-2 蛋白质组进行的 CTL 表位预测分析，这些表位缺乏可能刺激不想要的 T2 反应的结合特性。未来的研究将需要评估这些表位作为刺激针对 SARS-COV-2 的保护性 CTL 反应的多价亚单位疫苗候选物。
