Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches.
Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches.
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DOI：
10.1016/j.vaccine.2020.10.016
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发表时间：
2020-11-10
期刊：
影响因子：
5.5
通讯作者：
Ghahremani F
中科院分区：
文献类型：
--
作者：
Safavi A;Kefayat A;Mahdevar E;Abiri A;Ghahremani F
该疫苗由SARS-CoV-2非结构蛋白的免疫显性区域组成。此外，刺突蛋白的功能区被并入疫苗构建体中。最终的疫苗构建体含有多个CD 8+和CD 4+重叠表位。此外，它含有多个IFN-γ诱导的线性和构象B细胞表位。它与TLR-4/MD形成显著的相互作用和稳定的复合物。DNA疫苗通过最终疫苗构建体的反向翻译来设计。SARS-CoV-2导致一种称为COVID-19的严重呼吸道疾病。目前，全球卫生正面临其毁灭性的爆发。然而，到目前为止还没有针对这种病毒的疫苗。本研究设计了一种新的抗SARS-CoV-2的多表位疫苗，以激发先天性和适应性免疫应答。利用多种免疫信息学工具筛选SARS-CoV-2的6个非结构蛋白（nsp 7、nsp 8、nsp 9、nsp 10、nsp 12和nsp 14）的免疫优势区，以激发T细胞免疫应答。此外，选择SARS-CoV-2刺突蛋白功能区（400-510个残基）的免疫显性片段用于诱导中和抗体产生。所选区域的序列通过弗林蛋白酶敏感接头（RVRR）彼此连接。此外，使用（EAAAK）3接头将作为TLR-4/MD复合物的众所周知的激动剂的β-防御素的功能区添加在疫苗的N-末端。此外，通过GPGPG和A（EAAAK）2A接头在疫苗的C末端使用CD 4 + T辅助表位PADRE以形成最终的疫苗构建体。分析了最终疫苗构建体的理化性质、致敏性、抗原性、功能性和群体覆盖率。最终的疫苗构建体是免疫原性的、非变应原的和无功能的蛋白质，其含有多个CD 8+和CD 4+重叠表位、IFN-γ诱导表位、线性和构象B细胞表位。分子对接和动力学模拟结果表明，它与TLR-4/MD能形成稳定而显著的相互作用。HLA-I和II疫苗的全球人口覆盖率估计分别为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。虽然设计的疫苗在计算机上表现出高效力，但还需要进一步的实验验证。
The vaccine is composed of immunodominant regions of SARS-CoV-2 non-structural proteins. Also, the functional region of the spike protein is incorporated in the vaccine construct. The final vaccine construct contains multiple CD8+ and CD4+ overlapping epitopes Also, it contains multiple IFN-γ inducing, linear and conformational B cell epitopes. It forms significant interactions and stable complex with TLR-4/MD. The DNA vaccine is designed by reverse translation of the final vaccine construct. 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.
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影响因子：
14.9
作者：
Comeau, SR;Gatchell, DW;Camacho, CJ
通讯作者：
Camacho, CJ
影响因子：
9.5
作者：
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DOI：
10.1080/07391102.2020.1770127
发表时间：
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影响因子：
4.4
作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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