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基于 SARS-CoV-2 结构蛋白的 B 细胞和 T 细胞表位的生物信息学分析及其与新兴变异株和其他人类冠状病毒的潜在交叉反应性。

Bioinformatic Analysis of B- and T-cell Epitopes from SARS-CoV-2 Structural Proteins and their Potential Cross-reactivity with Emerging Variants and other Human Coronaviruses.

机构信息

Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.

Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México; Consejo Nacional de Ciencia y Tecnología, Ciudad de México, México.

出版信息

Arch Med Res. 2022 Nov;53(7):694-710. doi: 10.1016/j.arcmed.2022.10.007. Epub 2022 Nov 3.

Abstract

BACKGROUND

The mutations in SARS-CoV-2 variants of concern (VOC) facilitate the virus' escape from the neutralizing antibodies induced by vaccines. However, the protection from hospitalization and death is not significantly diminished. Both vaccine boosters and infection improve immune responses and provide protection, suggesting that conserved and/or cross-reactive epitopes could be involved. While several important T- and B-cell epitopes have been identified, mainly in the S protein, the M and N proteins and their potential cross-reactive epitopes with other coronaviruses remain largely unexplored.

AIMS

To identify and map new potential B- and T-cell epitopes within the SARS-CoV-2 S, M and N proteins, as well as cross-reactive epitopes with human coronaviruses.

METHODS

Different bioinformatics tools were used to: i) Identify new and compile previously-reported B-and T-cell epitopes from SARS-CoV-2 S, M and N proteins; ii) Determine the mutations in S protein from VOC that affect B- and T-cell epitopes, and; iii) Identify cross-reactive epitopes with coronaviruses relevant to human health.

RESULTS

New, potential B- and T-cell epitopes from S, M and N proteins as well as cross-reactive epitopes with other coronaviruses were found and mapped within the proteins' structures.

CONCLUSION

Numerous potential B- and T-cell epitopes were found in S, M and N proteins, some of which are conserved between coronaviruses. VOCs present mutations within important epitopes in the S protein; however, a significant number of other epitopes remain unchanged. The epitopes identified here may contribute to augmenting the protective response to SARS-CoV-2 and its variants induced by infection and/or vaccination, and may also be used for the rational design of novel broad-spectrum coronavirus vaccines.

摘要

背景

SARS-CoV-2 变体中的突变可使病毒逃避疫苗诱导的中和抗体。然而,住院和死亡的保护作用并未显著降低。疫苗加强针和感染都可以改善免疫反应并提供保护,这表明保守和/或交叉反应性表位可能参与其中。虽然已经确定了几个重要的 T 细胞和 B 细胞表位,主要在 S 蛋白中,但 M 和 N 蛋白及其与其他冠状病毒的潜在交叉反应性表位在很大程度上仍未得到探索。

目的

鉴定和绘制 SARS-CoV-2 S、M 和 N 蛋白内的新潜在 B 细胞和 T 细胞表位,以及与人类冠状病毒的交叉反应性表位。

方法

使用不同的生物信息学工具:i)从 SARS-CoV-2 S、M 和 N 蛋白中鉴定和编译新的和先前报道的 B 细胞和 T 细胞表位;ii)确定 VOC 中影响 B 细胞和 T 细胞表位的 S 蛋白突变;iii)鉴定与人类健康相关的冠状病毒的交叉反应性表位。

结果

在 S、M 和 N 蛋白的结构内发现并绘制了新的、潜在的 B 细胞和 T 细胞表位以及与其他冠状病毒的交叉反应性表位。

结论

在 S、M 和 N 蛋白中发现了大量潜在的 B 细胞和 T 细胞表位,其中一些在冠状病毒之间是保守的。VOC 在 S 蛋白中的重要表位中存在突变;然而,大量其他表位保持不变。这里鉴定的表位可能有助于增强感染和/或接种疫苗引起的对 SARS-CoV-2 及其变体的保护性反应,也可用于合理设计新型广谱冠状病毒疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c43c/9633039/2b1285d3e70c/gr1_lrg.jpg

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