Elsevier

Virology

Volume 559, July 2021, Pages 1-9
Virology

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

https://doi.org/10.1016/j.virol.2021.03.009Get rights and content
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Highlights

  • Inducible EGFP and Luciferase dual reporters target cell line.

  • Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) to SARS-CoV-2 spike protein.

  • Cell lysis mediated primarily via the NK FcγRIIIa receptor (CD16).

  • Functional SARS-CoV-2 spike (S) protein-based ADCC antibody assay.

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.

Keywords

SARS-CoV-2
Antibody-dependent cell-mediated cytotoxicity (ADCC)
COVID-19
Spike (S) protein
NK cells
FcγRIIIa receptor (CD16)

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