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功能性抗体依赖的细胞介导的细胞毒性（ADCC）针对 SARS-CoV-2 刺突蛋白的发展和动力学。

The development and kinetics of functional antibody-dependent cell-mediated cytotoxicity (ADCC) to SARS-CoV-2 spike protein.

机构信息

Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States; Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Atlanta, GA, United States.

Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States.

出版信息

Virology. 2021 Jul;559:1-9. doi: 10.1016/j.virol.2021.03.009. Epub 2021 Mar 19.

DOI:10.1016/j.virol.2021.03.009
PMID:33774551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7975276/
Abstract

Since the COVID-19 pandemic, functional non-neutralizing antibody responses to SARS-CoV-2, including antibody-dependent cell-mediated cytotoxicity (ADCC), are poorly understood. We developed an ADCC assay utilizing a stably transfected, dual-reporter target cell line with inducible expression of a SARS-CoV-2 spike protein on the cell surface. Using this assay, we analyzed 61 convalescent serum samples from adults with PCR-confirmed COVID-19 and 15 samples from healthy uninfected controls. We found that 56 of 61 convalescent serum samples induced ADCC killing of SARS-CoV-2 S target cells, whereas none of the 15 healthy controls had detectable ADCC. We then found a modest decline in ADCC titer over a median 3-month follow-up in 21 patients who had serial samples available for analysis. We confirmed that the antibody-dependent target cell lysis was mediated primarily via the NK FcγRIIIa receptor (CD16). This ADCC assay had high sensitivity and specificity for detecting serologic immune responses to SARS-CoV-2.

摘要

自 COVID-19 大流行以来，人们对 SARS-CoV-2 的功能性非中和抗体反应（包括抗体依赖性细胞介导的细胞毒性作用（ADCC））了解甚少。我们开发了一种 ADCC 测定法，利用稳定转染的双报告靶细胞系，该细胞系在细胞表面上可诱导表达 SARS-CoV-2 刺突蛋白。使用该测定法，我们分析了 61 份来自 PCR 确诊 COVID-19 的成年患者的恢复期血清样本和 15 份来自健康未感染者的对照样本。我们发现，61 份恢复期血清样本中有 56 份诱导了对 SARS-CoV-2 S 靶细胞的 ADCC 杀伤作用，而 15 份健康对照样本均未检测到 ADCC。然后，我们发现在 21 名可提供连续样本进行分析的患者中，ADCC 效价在中位 3 个月随访期间略有下降。我们证实，抗体依赖性靶细胞裂解主要通过 NK FcγRIIIa 受体（CD16）介导。该 ADCC 测定法对 SARS-CoV-2 的血清免疫反应具有很高的灵敏度和特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/ebee66887773/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/6441ebe092ad/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/02fb4dd3d8a5/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/7f6eda10c663/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/a9cd4290e714/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/ebee66887773/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/6441ebe092ad/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/02fb4dd3d8a5/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/7f6eda10c663/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/a9cd4290e714/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e1/7975276/ebee66887773/gr5_lrg.jpg

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