Zaheer Tahreem, Waseem Maaz, Waqar Walifa, Dar Hamza Arshad, Shehroz Muhammad, Naz Kanwal, Ishaq Zaara, Ahmad Tahir, Ullah Nimat, Bakhtiar Syeda Marriam, Muhammad Syed Aun, Ali Amjad
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Department of Biotechnology, Virtual University of Pakistan, Peshawar, Pakistan.
PeerJ. 2020 Aug 3;8:e9541. doi: 10.7717/peerj.9541. eCollection 2020.
The coronavirus SARS-CoV-2 is a member of the Coronaviridae family that has caused a global public health emergency. Currently, there is no approved treatment or vaccine available against it. The current study aimed to cover the diversity of SARS-CoV-2 strains reported from all over the world and to design a broad-spectrum multi-epitope vaccine using an immunoinformatics approach.
For this purpose, all available complete genomes were retrieved from GISAID and NGDC followed by genome multiple alignments to develop a global consensus sequence to compare with the reference genome. Fortunately, comparative genomics and phylogeny revealed a significantly high level of conservation between the viral strains. All the Open Reading Frames (ORFs) of the reference sequence NC_045512.2 were subjected to epitope mapping using CTLpred and HLApred, respectively. The predicted CTL epitopes were then screened for antigenicity, immunogenicity and strong binding affinity with HLA superfamily alleles. HTL predicted epitopes were screened for antigenicity, interferon induction potential, overlapping B cell epitopes and strong HLA DR binding potential. The shortlisted epitopes were arranged into two multi-epitope sequences, Cov-I-Vac and Cov-II-Vac, and molecular docking was performed with Toll-Like Receptor 8 (TLR8).
The designed multi-epitopes were found to be antigenic and non-allergenic. Both multi-epitopes were stable and predicted to be soluble in an expression system. The molecular docking with TLR8 also demonstrated that they have a strong binding affinity and immunogenic potential. These in silico analyses suggest that the proposed multi-epitope vaccine can effectively evoke an immune response.
冠状病毒SARS-CoV-2是冠状病毒科的成员，已引发全球公共卫生紧急事件。目前，尚无针对它的获批治疗方法或疫苗。当前的研究旨在涵盖全球报道的SARS-CoV-2毒株的多样性，并使用免疫信息学方法设计一种广谱多表位疫苗。
为此，从全球共享流感数据倡议组织（GISAID）和国家基因组科学数据中心（NGDC）检索所有可用的完整基因组，随后进行基因组多重比对以开发全球共识序列，以便与参考基因组进行比较。幸运的是，比较基因组学和系统发育分析显示病毒毒株之间存在显著高水平的保守性。参考序列NC_045512.2的所有开放阅读框（ORF）分别使用CTLpred和HLApred进行表位映射。然后筛选预测的CTL表位的抗原性、免疫原性以及与HLA超家族等位基因的强结合亲和力。筛选HTL预测的表位的抗原性、干扰素诱导潜力、重叠B细胞表位以及与HLA DR的强结合潜力。将入围的表位排列成两个多表位序列，即Cov-I-Vac和Cov-II-Vac，并与Toll样受体8（TLR8）进行分子对接。
发现设计的多表位具有抗原性且无致敏性。两个多表位均稳定，预计可在表达系统中溶解。与TLR8的分子对接还表明它们具有强结合亲和力和免疫原性潜力。这些计算机模拟分析表明，所提出的多表位疫苗可有效引发免疫反应。
