SARS-CoV-2 causes a severe respiratory disease called COVID-19. Currently, global health is facing its devastating outbreak. However, there is no vaccine available against this virus up to now. In this study, a novel multi-epitope vaccine against SARS-CoV-2 was designed to provoke both innate and adaptive immune responses. The immunodominant regions of six non-structural proteins (nsp7, nsp8, nsp9, nsp10, nsp12 and nsp14) of SARS-CoV-2 were selected by multiple immunoinformatic tools to provoke T cell immune response. Also, immunodominant fragment of the functional region of SARS-CoV-2 spike (400–510 residues) protein was selected for inducing neutralizing antibodies production. The selected regions’ sequences were connected to each other by furin-sensitive linker (RVRR). Moreover, the functional region of β-defensin as a well-known agonist for the TLR-4/MD complex was added at the N-terminus of the vaccine using (EAAAK)3 linker. Also, a CD4 + T-helper epitope, PADRE, was used at the C-terminal of the vaccine by GPGPG and A(EAAAK)2A linkers to form the final vaccine construct. The physicochemical properties, allergenicity, antigenicity, functionality and population coverage of the final vaccine construct were analyzed. The final vaccine construct was an immunogenic, non-allergen and unfunctional protein which contained multiple CD8 + and CD4 + overlapping epitopes, IFN-γ inducing epitopes, linear and conformational B cell epitopes. It could form stable and significant interactions with TLR-4/MD according to molecular docking and dynamics simulations. Global population coverage of the vaccine for HLA-I and II were estimated 96.2% and 97.1%, respectively. At last, the final vaccine construct was reverse translated to design the DNA vaccine. Although the designed vaccine exhibited high efficacy in silico, further experimental validation is necessary.

SARS-CoV-2导致严重的呼吸道疾病，称为COVID-19。当前，全球健康正面临着毁灭性的爆发。但是，到目前为止，尚无针对这种病毒的疫苗。在这项研究中，针对SARS-CoV-2的新型多表位疫苗旨在激发先天和适应性免疫应答。通过多种免疫信息学工具选择SARS-CoV-2的六个非结构蛋白（nsp7，nsp8，nsp9，nsp10，nsp12和nsp14）的免疫优势区域，以激发T细胞免疫应答。此外，还选择了SARS-CoV-2穗蛋白（400-510个残基）功能区的免疫优势片段来诱导中和抗体的产生。所选区域的序列通过弗林蛋白酶敏感性接头（RVRR）彼此连接。此外，使用（EAAAK）3接头在疫苗的N端添加了作为防御TLR-4 / MD复合物的激动剂的β-防御素功能区。同样，CDPG + T辅助抗原决定簇PADRE被GPGPG和A（EAAAK）2A接头用于疫苗的C末端，形成最终的疫苗构建体。分析了最终疫苗构建体的理化特性，致敏性，抗原性，功能性和种群覆盖率。最终的疫苗构建体是一种免疫原性，非过敏原和无功能的蛋白质，其中包含多个CD8 +和CD4 +重叠表位，IFN-γ诱导表位，线性和构象B细胞表位。根据分子对接和动力学模拟，它可以与TLR-4 / MD形成稳定且重要的相互作用。HLA-I和II疫苗的全球人口覆盖率分别估计为96.2％和97.1％。最后，将最终的疫苗构建体反向翻译以设计DNA疫苗。尽管设计的疫苗显示出高功效在计算机上，需要进一步的实验验证。