A novel Ebola virus antibody-dependent cell-mediated cytotoxicity (Ebola ADCC) assay

• Type of Material: Article
• Authors: Karnail Singh, Emory University; Bishal Marasini, Cincinnati Children’s Hospital Medical Center; Xuemin Chen, Emory University; Paul Spearman, Emory University
• Language: English
• Date: 2018-09-01
• Publisher: ELSEVIER SCIENCE BV
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jim.2018.06.002
• Title of Journal or Parent Work: JOURNAL OF IMMUNOLOGICAL METHODS
• Volume: 460
• Start Page: 10
• End Page: 16
• Keywords: Zaire; Life Sciences & Biomedicine; Ebola viral disease; PROTECTS NONHUMAN-PRIMATES; Biochemistry & Molecular Biology; Biochemical Research Methods; VACCINE; Ebolavirus; Science & Technology; ADCC; Immunology; Ebola glycoprotein; INFECTION

Abstract

Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potential mechanism through which anti-Ebola antibodies may mediate protection. We developed a robust Ebola-specific ADCC assay for use in ongoing trials of Ebola vaccines. Stable cell lines for inducible Zaire ebolavirus glycoprotein (EBOV GP) expression were developed to provide a uniform source of target cells in the assay, and were combined with an existing human natural killer (NK) cell line as the effector cell. When applied to commercially available anti-EBOV GP monoclonal antibodies, the assay clearly differentiated antibody with high ADCC activity from those with low or no ADCC activity. Anti-EBOV ADCC activity was also detected in plasma samples from rhesus macaques immunized with a candidate Ebola vaccine. The Ebola ADCC assay reported here will be a useful tool in studying the functionality of anti-EBOV GP antibodies elicited by Ebola vaccines in ongoing and future clinical trials.