Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30752
Title: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2.
Austin Authors: Wines, Bruce D;Kurtovic, Liriye;Trist, Halina M;Esparon, Sandra;Lopez, Ester;Chappin, Klasina;Chan, Li-Jin;Mordant, Francesca L;Lee, Wen Shi;Gherardin, Nicholas A;Patel, Sheila K ;Hartley, Gemma E;Pymm, Phillip;Cooney, James P;Beeson, James G;Godfrey, Dale I;Burrell, Louise M ;van Zelm, Menno C;Wheatley, Adam K;Chung, Amy W;Tham, Wai-Hong;Subbarao, Kanta;Kent, Stephen J;Hogarth, P Mark
Affiliation: Life Sciences, Burnet Institute, Melbourne, VIC, Australia..
World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia..
Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia..
Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Alfred Hospital, Melbourne, VIC, Australia..
Department of Microbiology, Monash University, Clayton VIC, Australia..
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia..
Medicine (University of Melbourne)
Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia..
Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia..
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia..
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia..
Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia..
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia..
Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia..
Issue Date: 28-Jul-2022
Date: 2022
Publication information: Frontiers in Immunology 2022; 13: 889372
Abstract: Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens.
URI: https://ahro.austin.org.au/austinjspui/handle/1/30752
DOI: 10.3389/fimmu.2022.889372
ORCID: 0000-0002-0626-1899
0000-0003-1863-7539
Journal: Frontiers in Immunology
PubMed URL: 35967361
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35967361/
Type: Journal Article
Subjects: ACE2-Fc
ADCC
COVID-19
SARS-CoV-2
antibody effector function
complement
coronavirus
neutralization
Appears in Collections:Journal articles

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