Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

BD Wines; L Kurtovic; HM Trist; S Esparon; E Lopez; K Chappin; LJ Chan; FL Mordant; WS Lee; NA Gherardin; SK Patel; GE Hartley; P Pymm; JP Cooney; JG Beeson; DI Godfrey; LM Burrell; MC van Zelm; AK Wheatley; AW Chung; WH Tham; K Subbarao; SJ Kent; PM Hogarth

Journal article

Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

BD Wines, L Kurtovic, HM Trist, S Esparon, E Lopez, K Chappin, LJ Chan, FL Mordant, WS Lee, NA Gherardin, SK Patel, GE Hartley, P Pymm, JP Cooney, JG Beeson, DI Godfrey, LM Burrell, MC van Zelm, AK Wheatley, AW Chung Show all

Frontiers in Immunology | FRONTIERS MEDIA SA | Published : 2022

DOI: 10.3389/fimmu.2022.889372

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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 n..

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University of Melbourne Researchers

Li Jin Chan Author

Francesca Mordant Author

Wen Shi Lee Author

Nicholas Gherardin Author

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Awarded by Department of Health, Australian Government

Funding Acknowledgements

The Medical Research Future Fund (MRFF 2002073) and Victorian State Government COVID research funding supported the research of AW, DG, W-HT, SK, PH, and SP, LB (1175865) with contribution from the Victorian Operational Infrastructure Support Program and Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme. NHMRC project grants supported PH, BW. (1145303). Investigator Grants are held by JB (1173046), KS (1177174) and DG (2008913) and program grants by SK (1149990), LB (1055214). DG (1117766), W-HT, SK, MZ (1117687) and AW receive National Health and Medical Research Council (NHMRC) fellowships. DG is supported by the Australian Research Council (ARC; CE140100011). NG was supported by an ARC DECRA Fellowship (DE210100705). SP and LB funded by a Heart Foundation Vanguard Grant (105798). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. W-HT is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z).