Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany.
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.
Front Immunol. 2021 May 20;12:688436. doi: 10.3389/fimmu.2021.688436. eCollection 2021.
Adaptive immune responses to structural proteins of the virion play a crucial role in protection against coronavirus disease 2019 (COVID-19). We therefore studied T cell responses against multiple SARS-CoV-2 structural proteins in a large cohort using a simple, fast, and high-throughput approach.
An automated interferon gamma release assay (IGRA) for the Nucleocapsid (NC)-, Membrane (M)-, Spike-C-terminus (SCT)-, and N-terminus-protein (SNT)-specific T cell responses was performed using fresh whole blood from study subjects with convalescent, confirmed COVID-19 (n = 177, more than 200 days post infection), exposed household members (n = 145), and unexposed controls (n = 85). SARS-CoV-2-specific antibodies were assessed using Elecsys Anti-SARS-CoV-2 (Ro-N-Ig) and Anti-SARS-CoV-2-ELISA (IgG) (EI-S1-IgG).
156 of 177 (88%) previously PCR confirmed cases were still positive by Ro-N-Ig more than 200 days after infection. In T cells, most frequently the M-protein was targeted by 88% seropositive, PCR confirmed cases, followed by SCT (85%), NC (82%), and SNT (73%), whereas each of these antigens was recognized by less than 14% of non-exposed control subjects. Broad targeting of these structural virion proteins was characteristic of convalescent SARS-CoV-2 infection; 68% of all seropositive individuals targeted all four tested antigens. Indeed, anti-NC antibody titer correlated loosely, but significantly with the magnitude and breadth of the SARS-CoV-2-specific T cell response. Age, sex, and body mass index were comparable between the different groups.
SARS-CoV-2 seropositivity correlates with broad T cell reactivity of the structural virus proteins at 200 days after infection and beyond. The SARS-CoV-2-IGRA can facilitate large scale determination of SARS-CoV-2-specific T cell responses with high accuracy against multiple targets.
针对病毒结构蛋白的适应性免疫反应在预防 2019 年冠状病毒病（COVID-19）方面起着至关重要的作用。因此，我们使用一种简单、快速且高通量的方法，在一个大的队列中研究了针对多种 SARS-CoV-2 结构蛋白的 T 细胞反应。
使用来自恢复期、确诊 COVID-19（n=177，感染后 200 天以上）、暴露于家庭环境中的成员（n=145）和未暴露于家庭环境中的对照者（n=85）的新鲜全血，使用 Nucleocapsid（NC）、Membrane（M）、Spike-C-terminus（SCT）和 N-terminus-protein（SNT）特异性 T 细胞反应的自动化干扰素 γ释放测定（IGRA）进行 SARS-CoV-2 特异性 T 细胞反应的检测。使用 Elecsys Anti-SARS-CoV-2（Ro-N-Ig）和 Anti-SARS-CoV-2-ELISA（IgG）（EI-S1-IgG）检测 SARS-CoV-2 特异性抗体。
177 例经 PCR 确诊的病例中，156 例（88%）在感染后 200 天以上仍通过 Ro-N-Ig 检测呈阳性。在 T 细胞中，最常见的是 M 蛋白被 88%的血清阳性、PCR 确诊的病例所靶向，其次是 SCT（85%）、NC（82%）和 SNT（73%），而这些抗原中每个抗原都被不到 14%的未暴露对照者识别。这些结构病毒蛋白的广泛靶向是恢复期 SARS-CoV-2 感染的特征；所有血清阳性个体中有 68%靶向了所有 4 种测试抗原。事实上，抗 NC 抗体滴度与 SARS-CoV-2 特异性 T 细胞反应的幅度和广度呈松散但显著的相关性。不同组之间的年龄、性别和体重指数相当。
SARS-CoV-2 血清阳性与感染后 200 天及以后针对多种靶标结构病毒蛋白的广泛 T 细胞反应相关。SARS-CoV-2-IGRA 可以促进针对多种靶标进行 SARS-CoV-2 特异性 T 细胞反应的大规模测定，具有很高的准确性。
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