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基于 SARS-CoV-2 刺突糖蛋白的多聚表位肽疫苗的免疫信息学设计。

Immuno-informatics design of a multimeric epitope peptide based vaccine targeting SARS-CoV-2 spike glycoprotein.

机构信息

Department of Cell Biology and Genetics, University of Lagos, Lagos, Nigeria.

Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Cape Town, South Africa.

出版信息

PLoS One. 2021 Mar 17;16(3):e0248061. doi: 10.1371/journal.pone.0248061. eCollection 2021.

DOI:10.1371/journal.pone.0248061
PMID:33730022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7968690/
Abstract

Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We, therefore, propose that potential vaccine designs consider this approach.

摘要

开发针对严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)感染的有效疫苗对于遏制 COVID-19 死亡和为全球提供免疫保护至关重要。我们采用生物信息学方法来辅助设计针对该病毒刺突蛋白的基于表位肽的疫苗。我们从结构上确定了五个具有潜在抗原性的 B 细胞抗原表位和总共 27 个不连续的 B 细胞表位,以用于抗体识别。我们鉴定了八个 CD8+ T 细胞 9 -mer 和 12 个 CD4+ T 细胞 14-15-mer 作为有前途的候选表位,它们分别假定受到大量 MHC I 和 II 等位基因的限制。我们利用这些信息构建了一种计算机模拟的嵌合肽疫苗,当克隆到 pET28a(+)载体中时,其翻译效率得到高度表达。通过我们的计算机测试,当作为同源初免-加强免疫时,该疫苗构建体被预测具有高抗原性和细胞介导的免疫性,佐剂接头触发 Toll 样受体 5。该疫苗还表现出 IgM 和 IgG 的增加以及一系列 Th1 和 Th2 细胞因子。在使用我们的免疫模拟进行 SARS-CoV-2 的计算机挑战时,抗原水平下降。因此,我们建议潜在的疫苗设计考虑这种方法。

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