ABSTRACT

Background

The novel SARS-CoV-2 coronavirus, the causative agent of the ongoing pandemic COVID-19 disease continues to infect people globally and has infected millions of humans worldwide. However, no effective vaccine against this virus exists.

Method

Using Immunoinformatics, epitopic sequences from multiple glycoproteins that play crucial role in pathogenesis were identified. Particularly, epitopes were mapped from conserved receptor-binding domain of spike protein which have been experimentally validated in SARS-CoV-1 as a promising target for vaccine development.

Results

A multi-epitopic vaccine construct comprising of B-cell, CTL, HTL epitopes was developed along with fusion of adjuvant and linkers. The epitopes identified herein are reported for the first time and were predicted to be highly antigenic, stable, nonallergen, nontoxic and displayed conservation across several SARS-CoV-2 isolates from different countries. Additionally, the epitopes associated with maximum HLA alleles and population coverage analysis shows the proposed epitopes would be a relevant representative of large proportion of the world population. A reliable three-dimensional structure of the vaccine construct was developed. Consequently, docking and molecular-dynamics simulation ensured the stable interaction between vaccine and innate-immune receptor.

中文翻译：

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设计一种有效的多表位疫苗，以显示与不同的HLA分子的相互作用，以实现有效的体液和细胞免疫反应，从而预防COVID-19感染。

摘要

背景

新型SARS-CoV-2冠状病毒是正在进行的大流行COVID-19疾病的病原体，继续在全球范围内感染人类，并已感染全球数百万人。但是，不存在针对这种病毒的有效疫苗。

方法

使用免疫信息学，鉴定了多种糖蛋白的抗原决定簇序列，它们在发病机理中起着至关重要的作用。特别地，从穗蛋白的保守受体结合结构域定位表位，其已经在SARS-CoV-1中被实验验证为疫苗开发的有希望的靶标。

结果

与佐剂和接头的融合一起，开发了包含B细胞，CTL，HTL表位的多表位疫苗构建体。本文鉴定的表位是首次报道，并被预测为高度抗原性，稳定，非过敏原，无毒，并且在来自不同国家的几种SARS-CoV-2分离株中显示出保守性。此外，与最大的HLA等位基因和人群覆盖率分析相关的表位表明，拟议的表位将成为世界人口很大比例的相关代表。开发了疫苗构建体的可靠的三维结构。因此，对接和分子动力学模拟确保了疫苗与先天免疫受体之间的稳定相互作用。