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在 COVID-19 和恢复期,针对 SARS-CoV-2 刺突和核衣壳蛋白快速产生持久的 B 细胞记忆。

Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence.

机构信息

Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.

Department of Allergy, Immunology & Respiratory Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia.

出版信息

Sci Immunol. 2020 Dec 22;5(54). doi: 10.1126/sciimmunol.abf8891.

Abstract

Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM or IgG1 and continued to rise until 150 days. RBD-specific IgG Bmem were predominantly CD27, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

摘要

SARS-CoV-2 感染后持久的免疫受到质疑,因为恢复期血清抗体下降。然而,功能性免疫是由长寿的记忆 T 和 B(Bmem)细胞介导的。因此,我们生成了带有荧光标记的刺突受体结合域(RBD)和核衣壳蛋白(NCP)的四聚体,以确定 COVID-19 患者中 SARS-CoV-2 特异性 Bmem 细胞的寿命和免疫表型。从 25 名 COVID-19 患者中获得了总共 36 份血液样本,这些患者的症状发作后 4 至 242 天,包括 11 对样本。虽然所有患者均检测到针对 RBD 和 NCP 的血清 IgG,但抗体水平在症状发作后 20 天开始下降。RBD 和 NCP 特异性 Bmem 细胞主要表达 IgM 或 IgG1,并持续升高至 150 天。RBD 特异性 IgG Bmem 主要为 CD27,数量与循环滤泡辅助 T 细胞数量显著相关。因此,SARS-CoV-2 抗体反应在恢复期收缩,同时 RBD 和 NCP 特异性 Bmem 细胞持续存在。SARS-CoV-2 特异性 Bmem 细胞的流式细胞术检测可用于检测 COVID-19 感染或疫苗接种后的长期免疫记忆。

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