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An in-depth in silico and immunoinformatics approach for designing a potential multi-epitope construct for the effective development of vaccine to combat against SARS-CoV-2 encompassing variants of concern and interest
Computers in Biology and Medicine ( IF 7.7 ) Pub Date : 2021-07-30 , DOI: 10.1016/j.compbiomed.2021.104703
Abdullah Al Saba 1 , Maisha Adiba 1 , Piyal Saha 1 , Md Ismail Hosen 1 , Sajib Chakraborty 2 , A H M Nurun Nabi 1
Affiliation  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest of the several viral pathogens that have acted as a threat to human health around the world. Thus, to prevent COVID-19 and control the outbreak, the development of vaccines against SARS-CoV-2 is one of the most important strategies at present. The study aimed to design a multi-epitope vaccine (MEV) against SARS-CoV-2. For the development of a more effective vaccine, 1549 nucleotide sequences were taken into consideration, including the variants of concern (B.1.1.7, B.1.351, P.1 and, B.1.617.2) and variants of interest (B.1.427, B.1.429, B.1.526, B.1.617.1 and P.2). A total of 11 SARS-CoV-2 proteins (S, N, E, M, ORF1ab polyprotein, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10) were targeted for T-cell epitope prediction and S protein was targeted for B-cell epitope prediction. MEV was constructed using linkers and adjuvant beta-defensin. The vaccine construct was verified, based on its antigenicity, physicochemical properties, and its binding potential, with toll-like receptors (TLR2, TLR4), ACE2 receptor and B cell receptor. The selected vaccine construct showed considerable binding with all the receptors and a significant immune response, including elevated antibody titer and B cell population along with augmented activity of TH cells, Tc cells and NK cells. Thus, immunoinformatics and in silico-based approaches were used for constructing MEV which is capable of eliciting both innate and adaptive immunity. In conclusion, the vaccine construct developed in this study has all the potential for the development of a next-generation vaccine which may in turn effectively combat the new variants of SARS-CoV-2 identified so far. However, in vitro and animal studies are warranted to justify our findings for its utility as probable preventive measure.



中文翻译:

一种深入的计算机和免疫信息学方法,用于设计潜在的多表位构建体,以有效开发疫苗以对抗 SARS-CoV-2,其中包含令人关注和感兴趣的变体

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 是对全球人类健康构成威胁的几种病毒病原体中最新的一种。因此,为预防 COVID-19 和控制疫情,开发针对 SARS-CoV-2 的疫苗是目前最重要的策略之一。该研究旨在设计一种针对 SARS-CoV-2 的多表位疫苗 (MEV)。为了开发更有效的疫苗,考虑了 1549 个核苷酸序列,包括关注的变体(B.1.1.7、B.1.351、P.1 和 B.1.617.2)和感兴趣的变体(B .1.427、B.1.429、B.1.526、B.1.617.1 和 P.2)。共有 11 种 SARS-CoV-2 蛋白(S、N、E、M、ORF1ab 多蛋白、ORF3a、ORF6、ORF7a、ORF7 b, ORF8, ORF10) 用于 T 细胞表位预测,S 蛋白用于 B 细胞表位预测。MEV 是使用接头和佐剂 β-防御素构建的。根据其抗原性、理化特性及其与 Toll 样受体(TLR2、TLR4)、ACE2 受体和 B 细胞受体的结合潜力,验证了疫苗构建体。选定的疫苗构建体显示出与所有受体的显着结合和显着的免疫反应,包括升高的抗体滴度和 B 细胞群以及 T H细胞、Tc 细胞和 NK 细胞的增强活性。因此,免疫信息学和计算机基于的方法被用于构建能够引发先天免疫和适应性免疫的 MEV。总之,本研究开发的疫苗结构具有开发下一代疫苗的所有潜力,而下一代疫苗可能反过来有效对抗迄今为止发现的 SARS-CoV-2 新变种。然而,体外和动物研究有必要证明我们的发现作为可能的预防措施的效用。

更新日期:2021-08-03
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