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通过生物信息学阐明保守表位,以设计针对现有和新出现的值得关注的SARS-CoV-2变体的潜在候选疫苗。

Bioinformatic elucidation of conserved epitopes to design a potential vaccine candidate against existing and emerging SARS-CoV-2 variants of concern.

作者信息

Rastogi Amber, Gautam Sakshi, Kumar Manoj

机构信息

Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh, 160036, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Heliyon. 2024 Jul 23;10(15):e35129. doi: 10.1016/j.heliyon.2024.e35129. eCollection 2024 Aug 15.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 poses a significant adverse effects on health and economy globally. Due to mutations in genome, COVID-19 vaccine efficacy decreases. We used immuno-informatics to design a Multi epitope vaccine (MEV) candidate for SARS-CoV-2 variants of concern (VOCs). Hence, we predicted binders/epitopes MHC-I, CD8, MHC-II, CD4, and CTLs from spike, membrane and envelope proteins of VOCs. In addition, we assessed the conservation of these binders and epitopes across different VOCs. Subsequently, we designed MEV by combining the predicted CTL and CD4 epitopes from spike protein, peptide linkers, and an adjuvant. Further, we evaluated the binding of MEV candidate against immune receptors namely HLA class I histocompatibility antigen, HLA class II histocompatibility antigen, and TLR4, achieving binding scores of -1265.3, -1330.7, and -1337.9. Molecular dynamics and normal mode analysis revealed stable docking complexes. Moreover, immune simulation suggested MEV candidate elicits both innate and adaptive immune response. We anticipate that this conserved MEV candidate will provide protection from VOCs and emerging strains.

摘要

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)大流行对全球健康和经济造成了重大不利影响。由于基因组中的突变,COVID-19疫苗的效力降低。我们利用免疫信息学为关注的SARS-CoV-2变异株(VOCs)设计了一种多表位疫苗(MEV)候选物。因此,我们从VOCs的刺突蛋白、膜蛋白和包膜蛋白中预测了与主要组织相容性复合体I类(MHC-I)、CD8、MHC-II、CD4和细胞毒性T淋巴细胞(CTLs)结合的表位。此外,我们评估了这些结合表位在不同VOCs中的保守性。随后,我们通过组合来自刺突蛋白的预测CTL和CD4表位、肽接头和佐剂来设计MEV。此外,我们评估了MEV候选物与免疫受体即HLA I类组织相容性抗原、HLA II类组织相容性抗原和Toll样受体4(TLR4)的结合情况,结合得分分别为-1265.3、-1330.7和-1337.9。分子动力学和正常模式分析揭示了稳定的对接复合物。此外,免疫模拟表明MEV候选物可引发先天性和适应性免疫反应。我们预计这种保守的MEV候选物将为抵御VOCs和新出现的毒株提供保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8a5/11328099/172912bfee9e/gr1.jpg

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