Frontiers in Immunology (Jul 2022)
Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2
- Bruce D. Wines,
- Bruce D. Wines,
- Bruce D. Wines,
- Bruce D. Wines,
- Liriye Kurtovic,
- Liriye Kurtovic,
- Halina M. Trist,
- Sandra Esparon,
- Ester Lopez,
- Klasina Chappin,
- Li-Jin Chan,
- Li-Jin Chan,
- Francesca L. Mordant,
- Wen Shi Lee,
- Nicholas A. Gherardin,
- Sheila K. Patel,
- Gemma E. Hartley,
- Phillip Pymm,
- Phillip Pymm,
- James P. Cooney,
- James P. Cooney,
- James G. Beeson,
- James G. Beeson,
- James G. Beeson,
- James G. Beeson,
- Dale I. Godfrey,
- Louise M. Burrell,
- Menno C. van Zelm,
- Menno C. van Zelm,
- Adam K. Wheatley,
- Adam K. Wheatley,
- Amy W. Chung,
- Wai-Hong Tham,
- Wai-Hong Tham,
- Kanta Subbarao,
- Kanta Subbarao,
- Stephen J. Kent,
- Stephen J. Kent,
- Stephen J. Kent,
- P. Mark Hogarth,
- P. Mark Hogarth,
- P. Mark Hogarth
Affiliations
- Bruce D. Wines
- Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia
- Bruce D. Wines
- Life Sciences, Burnet Institute, Melbourne, VIC, Australia
- Bruce D. Wines
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Bruce D. Wines
- Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia
- Liriye Kurtovic
- Life Sciences, Burnet Institute, Melbourne, VIC, Australia
- Liriye Kurtovic
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Halina M. Trist
- Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia
- Sandra Esparon
- Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia
- Ester Lopez
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Klasina Chappin
- Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia
- Li-Jin Chan
- Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Li-Jin Chan
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- Francesca L. Mordant
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Wen Shi Lee
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Nicholas A. Gherardin
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Sheila K. Patel
- Department of Medicine, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
- Gemma E. Hartley
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Phillip Pymm
- Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Phillip Pymm
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- James P. Cooney
- Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- James P. Cooney
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- James G. Beeson
- Life Sciences, Burnet Institute, Melbourne, VIC, Australia
- James G. Beeson
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- James G. Beeson
- Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
- James G. Beeson
- 0Department of Microbiology, Monash University, Clayton VIC, Australia
- Dale I. Godfrey
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Louise M. Burrell
- Department of Medicine, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
- Menno C. van Zelm
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Menno C. van Zelm
- 1Department of Allergy, Immunology and Respiratory Medicine, Central Clinical School, Alfred Hospital, Melbourne, VIC, Australia
- Adam K. Wheatley
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Adam K. Wheatley
- 2Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia
- Amy W. Chung
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Wai-Hong Tham
- Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Wai-Hong Tham
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- Kanta Subbarao
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Kanta Subbarao
- 3World 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
- Stephen J. Kent
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Stephen J. Kent
- 2Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia
- Stephen J. Kent
- 4Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia
- P. Mark Hogarth
- Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia
- P. Mark Hogarth
- Life Sciences, Burnet Institute, Melbourne, VIC, Australia
- P. Mark Hogarth
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
- DOI
- https://doi.org/10.3389/fimmu.2022.889372
- Journal volume & issue
-
Vol. 13
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.
Keywords
