在未接种疫苗或接种过 SARS-CoV-2 疫苗的患者中，刺突特异性 TCRβ 库具有明显特征。

The spike-specific TCRβ repertoire shows distinct features in unvaccinated or vaccinated patients with SARS-CoV-2 infection.

机构信息

Department of Experimental and Clinical Medicine, University "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.

Interdepartmental Centre of Services, University "Magna Graecia", 88100, Catanzaro, Italy.

出版信息

J Transl Med. 2024 Jan 7;22(1):33. doi: 10.1186/s12967-024-04852-1.

DOI:10.1186/s12967-024-04852-1

PMID:38185632

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10771664/

Abstract

BACKGROUND

The evolving variants of SARS-CoV-2 may escape immunity from prior infections or vaccinations. It's vital to understand how immunity adapts to these changes. Both infection and mRNA vaccination induce T cells that target the Spike protein. These T cells can recognize multiple variants, such as Delta and Omicron, even if neutralizing antibodies are weakened. However, the degree of recognition can vary among people, affecting vaccine efficacy. Previous studies demonstrated the capability of T-cell receptor (TCR) repertoire analysis to identify conserved and immunodominant peptides with cross-reactive potential among variant of concerns. However, there is a need to extend the analysis of the TCR repertoire to different clinical scenarios. The aim of this study was to examine the Spike-specific TCR repertoire profiles in natural infections and those with combined natural and vaccine immunity.

METHODS

A T-cell enrichment approach and bioinformatic tools were used to investigate the Spike-specific TCRβ repertoire in peripheral blood mononuclear cells of previously vaccinated (n = 8) or unvaccinated (n = 6) COVID-19 patients.

RESULTS

Diversity and clonality of the TCRβ repertoire showed no significant differences between vaccinated and unvaccinated groups. When comparing the TCRβ data to public databases, 692 unique TCRβ sequences linked to S epitopes were found in the vaccinated group and 670 in the unvaccinated group. TCRβ clonotypes related to spike regions S135-177, S264-276, S319-350, and S448-472 appear notably more prevalent in the vaccinated group. In contrast, the S673-699 epitope, believed to have super antigenic properties, is observed more frequently in the unvaccinated group. In-silico analyses suggest that mutations in epitopes, relative to the main SARS-CoV-2 variants of concern, don't hinder their cross-reactive recognition by associated TCRβ clonotypes.

CONCLUSIONS

Our findings reveal distinct TCRβ signatures in vaccinated and unvaccinated individuals with COVID-19. These differences might be associated with disease severity and could influence clinical outcomes.

TRIAL REGISTRATION

FESR/FSE 2014-2020 DDRC n. 585, Action 10.5.12, noCOVID19@UMG.

摘要

背景

SARS-CoV-2 的不断演变的变体可能逃避先前感染或疫苗接种产生的免疫。了解免疫如何适应这些变化至关重要。感染和 mRNA 疫苗均可诱导针对 Spike 蛋白的 T 细胞。这些 T 细胞可以识别多种变体，如 Delta 和 Omicron，即使中和抗体减弱也是如此。然而，人与人之间的识别程度可能不同，从而影响疫苗的效果。先前的研究表明，T 细胞受体 (TCR) 谱分析具有识别关切变体之间具有交叉反应潜力的保守和免疫优势肽的能力。然而，需要将 TCR 谱分析扩展到不同的临床情况。本研究旨在检查自然感染和自然感染与联合疫苗免疫中 Spike 特异性 TCR 谱。

方法

使用 T 细胞富集方法和生物信息学工具来研究先前接种过疫苗（n=8）或未接种疫苗（n=6）的 COVID-19 患者外周血单个核细胞中的 Spike 特异性 TCRβ 谱。

结果

接种组和未接种组的 TCRβ 谱的多样性和克隆性无显著差异。将 TCRβ 数据与公共数据库进行比较时，在接种组中发现了 692 个与 S 表位相关的独特 TCRβ 序列，而在未接种组中发现了 670 个。与 Spike 区域 S135-177、S264-276、S319-350 和 S448-472 相关的 TCRβ 克隆型在接种组中更为普遍。相比之下，S673-699 表位被认为具有超级抗原特性，在未接种组中更频繁出现。计算机分析表明，与主要的 SARS-CoV-2 变体相比，表位中的突变不会阻碍其相关 TCRβ 克隆型的交叉反应识别。