Abstract
Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune response. In this review, we discuss recent studies, primarily using mouse models, that identified a role for Fc-FcγR interactions for optimal antibody-based protection against emerging and re-emerging virus infections.
Highlights
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Antibodies consist of two heavy and two light chains that form two distinct regions, the fragment antigen binding (Fab) region, which contains the variable region that binds to the antigen, and the fragment crystallizable (Fc) region, which interacts with host proteins, such as
The requirement of Fc effector functions for IgG-mediated protection in vivo can be be evaluated using a combination of IgG subclass switching, recombinant monoclonal antibody (mAb) variants evaluated using a combination of IgG subclass switching, recombinant mAb variants to to enhance or eliminate FcγR interactions, genetic knockout mice, and transgenic FcγR
Summary
Emerging viral infections are caused by newly discovered viruses or viruses that are increasing in incidence or geographical range. IgG can neutralize infection by directly blocking the viral replication cycle, form immune complexes that enhance phagocytosis through opsonization, and activate immune cells through Fc-Fc gamma receptor (FcγR) interactions (Figure 1). Viruses 2021, 13, 1037 with the Fc region of antibodies bound to viral proteins on the surface of infected cells can trigger clearance of infected cells through antibody-dependent cellular cytotoxicity (ADCC). During infectedand cellsantibody-dependent can trigger clearancecellular of infected cells through antibody-dependent cellular some viral infections, Fc-FcγR interactions assist in alternative pathways of virion cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) Emerging viral infections are a significant public health threat, and optimizing antibased protection through balanced engagement of Fc-mediated functions will result body-based protection through balanced engagement of Fc-mediated functions will resultin therapeutics. FcγR interactions for mAb-based therapies, primarily using mouse models, during emergand re-emerging virus infections.
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