Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Faculty of Allied Health Sciences, Kuwait University, Kuwait City, Kuwait.
Immunogenetics. 2021 Dec;73(6):459-477. doi: 10.1007/s00251-021-01228-3. Epub 2021 Sep 20.
Since 2019, the world was involved with SARS-CoV-2 and consequently, with the announcement by the World Health Organization that COVID-19 was a pandemic, scientific were an effort to obtain the best approach to combat this global dilemma. The best way to prevent the pandemic from spreading further is to use a vaccine against COVID-19. Here, we report the design of a recombinant multi-epitope vaccine against the four proteins spike or crown (S), membrane (M), nucleocapsid (N), and envelope (E) of SARS-CoV-2 using immunoinformatics tools. We evaluated the most antigenic epitopes that bind to HLA class 1 subtypes, along with HLA class 2, as well as B cell epitopes. Beta-defensin 3 and PADRE sequence were used as adjuvants in the structure of the vaccine. KK, GPGPG, and AAY linkers were used to fuse the selected epitopes. The nucleotide sequence was cloned into pET26b(+) vector using restriction enzymes XhoI and NdeI, and HisTag sequence was considered in the C-terminal of the construct. The results showed that the proposed candidate vaccine is a 70.87 kDa protein with high antigenicity and immunogenicity as well as non-allergenic and non-toxic. A total of 95% of the selected epitopes have conservancy with similar sequences. Molecular docking showed a strong binding between the vaccine structure and tool-like receptor (TLR) 7/8. The docking, molecular dynamics, and MM/PBSA analysis showed that the vaccine established a stable interaction with both structures of TLR7 and TLR8. Simulation of immune stimulation by this vaccine showed that it evokes immune responses related to humoral and cellular immunity.
自 2019 年以来,世界一直受到 SARS-CoV-2 的影响,随后世界卫生组织宣布 COVID-19 大流行,科学界努力寻找最佳方法来应对这一全球性难题。阻止大流行进一步传播的最佳方法是使用 COVID-19 疫苗。在这里,我们报告了使用免疫信息学工具针对 SARS-CoV-2 的四个蛋白刺突或冠状(S)、膜(M)、核衣壳(N)和包膜(E)设计的重组多表位疫苗。我们评估了与 HLA 类 1 亚型结合的最抗原表位,以及 HLA 类 2 和 B 细胞表位。β-防御素 3 和 PADRE 序列被用作疫苗结构中的佐剂。KK、GPGPG 和 AAY 接头用于融合所选表位。使用限制性内切酶 XhoI 和 NdeI 将核苷酸序列克隆到 pET26b(+)载体中,并在构建体的 C 末端考虑 HisTag 序列。结果表明,所提出的候选疫苗是一种 70.87 kDa 的蛋白质,具有高抗原性和免疫原性,同时具有非变应原性和非毒性。所选表位的 95%具有保守性,具有相似的序列。分子对接显示疫苗结构与工具样受体(TLR)7/8 之间具有很强的结合。对接、分子动力学和 MM/PBSA 分析表明,疫苗与 TLR7 和 TLR8 的两种结构均建立了稳定的相互作用。该疫苗免疫刺激的模拟表明,它引发与体液和细胞免疫相关的免疫反应。