A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8+ T cell test

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Congling Qiu , Bo Peng , Chanchan Xiao , Pengfei Chen , Lipeng Mao , Xiaolu Shi , Zhen Zhang , Ziquan Lv , Qiuying Lv , Xiaomin Zhang , Jiaxin Li , Yanhao Huang , Qinghua Hu , Guobing Chen , Xuan Zou , Xiaofeng Liang
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引用次数: 0

Abstract

Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8+ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8+ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8+ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8+ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8+ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2+ and HLA-A24+ donors, providing a novel method for SARS-CoV-2 infected case tracing.

通过表位特异性 CD8+ T 细胞检测鉴定 SARS-CoV-2 感染突变体的新方法
自 2019 年爆发冠状病毒病 2019(COVID-19)疫情以来,公共卫生系统面临着巨大的挑战。追踪严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)检测呈阳性的个体是阻断 SARS-CoV-2 传播链、降低 COVID-19 相关死亡率的关键一步。随着无症状感染的增加,很难通过流行病学调查和病毒全基因组测序来追踪无症状感染。然而,由于多种病毒亚型产生的中和抗体具有交叉反应性,中和抗体检测不能用于确定个人是否有感染特定亚型 SARS-CoV-2 的历史。我们招募了 4 名人类白细胞抗原 A2 (HLA-A2) 感染者、15 名接种了三剂灭活疫苗的患者和 30 名接种疫苗后出现突破性感染的患者,并讨论了一种病例追踪方法,以检测密切接触者外周血中表位特异性 CD8+ T 细胞、包括根据核糖核酸 (RNA) 测序和流式细胞仪数据进行准确的 HLA 分型,以及比较和鉴定 SARS-CoV-2 HLA-A2 和 HLA-A24 表位特异性 CD8+ T 细胞。我们从接种了三剂灭活疫苗的个体中观察到,CD8+ T 细胞对祖先表位的特异性明显高于对变异表位的特异性,变异表位相对于祖先表位的 CD8+ T 细胞的折合变化小于 1。这项研究形成了一种 "基于受试者外周血中表位特异性 CD8+ T 细胞比例了解 SARS-CoV-2 亚型感染史的方法",覆盖人群高达 46%,包括 HLA-A2+ 和 HLA-A24+ 供体,为 SARS-CoV-2 感染病例追踪提供了一种新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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