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

• Type of Material: Article
• Authors: Xuemin Chen, Emory University; Christina Rostad, Emory University; Larry Anderson, Emory University; He-Ying Sun, Emory University; Stacey A Lapp, Emory University; Kathy Stephens, Emory University; Laila Hussaini, Emory University; Theda Gibson, Emory University; Nadine Rouphael, Emory University; Evan Anderson, Emory University
• Language: English
• Date: 2021-03-25
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2021.03.009
• Title of Journal or Parent Work: VIROLOGY
• Volume: 559
• Start Page: 1
• End Page: 9
• Grant/Funding Information: This study was partly funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health to the Emory Vaccine and Treatment Evaluation Units [VTEU] HHSN272201300018I and 1 UM1 AI148576-01. Additional support was provided by the Center for Childhood Infections and Vaccines at Emory University and Children's Healthcare of Atlanta, and the Georgia Research Alliance.
• Keywords: NK cells; COVID-19; TARGET-CELLS; Fc gamma RIIIa receptor (CD16); SARS-CoV-2; Virology; Antibody-dependent cell-mediated cytotoxicity (ADCC); Spike (S) protein; Science & Technology; Life Sciences & Biomedicine; REPORTER; IN-VITRO; VACCINATION
• Research Categories: Health Sciences, Health Care Management; Health Sciences, Public Health

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.