ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1571835
This article is part of the Research TopicSARS-CoV-2 Vaccines Beyond the Pandemic EraView all 27 articles
Fc-Effector Functional Antibody Assays for SARS-CoV-2 Variants of Concern
Provisionally accepted
- 1School of Medicine, Emory University, Atlanta, United States
- 2Children's Healthcare of Atlanta, Atlanta, Georgia, United States
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Background: The Fc regions of antibodies mediate important effector cell functions such as antibodydependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), antibodydependent neutrophil phagocytosis (ADNP), and complement-dependent cytotoxicity (CDC). These functions enhance immune defense and infected cell clearance. This study evaluated the effect COVID-19 XBB1.5 booster vaccination on Fc-effector antibody responses to SARS-CoV-2. Methods: We developed four assays to evaluate the Fc-effector functions of SARS-CoV-2 antibodies. ADCC and CDC assays utilized stably transfected luciferase-based target cell lines expressing SARS-CoV-2 spike variants (Ancestral, Omicron XBB.1.5, and EG.5) to measure antibody-mediated lysis by effector cells. ADCP and ADNP were assessed by flow cytometry to measure phagocytosis of fluorescently labeled virus-like particles that display SARS-CoV-2 variant spike proteins. Serum samples from 20 healthy adult volunteers pre-and post-monovalent XBB.1.5 COVID-19 vaccine were analyzed for pseudovirus neutralizing and Fceffector antibodies.Results: Prior to administration of the COVID-19 XBB.1.5 booster vaccination, cross-neutralizing antibodies against XBB.1.5 and EG.5 variants were minimally detectable, while cross-functional Fc-effector antibodies were present at higher baseline levels. The COVID-19 XBB.1.5 booster vaccination significantly boosted both neutralizing and Fc-effector antibodies in magnitude and breadth. The greatest increase in neutralizing antibodies was against the XBB.1.5 strain, while Fc-effector functional antibodies had similar fold-increases in antibody titers against the breadth of SARS-CoV-2 variants tested. Neutralizing and Fc effector antibodies were most highly correlated at baseline (prior to booster vaccination) but were less correlated postvaccination, consistent with differential boosting of neutralizing vs Fc-effector antibodies by the monovalent vaccine. The COVID-19 XBB.1.5 booster vaccination significantly improved the magnitude, breadth, and quality of antibody responses to SARS-CoV-2. Combining Fc-mediated functional and neutralizing antibody assays provides a comprehensive model for understanding vaccine-induced immunity and optimizing vaccination strategies.
Keywords: ADCC, ADNP, ADCP, Non-neutralizing antibodies, Cytotoxicity, Phagocytosis, Complement deposition
Received: 06 Feb 2025; Accepted: 15 Apr 2025.
Copyright: © 2025 Chen, Li, Ciric, Gibson, Anderson and Rostad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Christina A. Rostad, School of Medicine, Emory University, Atlanta, United States
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