Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2
- Author(s)
- Wines, BD; Kurtovic, L; Trist, HM; Esparon, S; Lopez, E; Chappin, K; Chan, LJ; Mordant, FL; Lee, WS; Gherardin, NA; Patel, SK; Hartley, GE; Pymm, P; Cooney, JP; Beeson, JG; Godfrey, DI; Burrell, LM; van Zelm, MC; Wheatley, AK; Chung, AW; Tham, WH; Subbarao, K; Kent, SJ; Hogarth, PM;
- Journal Title
- Frontiers in Immunology
- 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.
- Publisher
- Frontiers Media
- Keywords
- *Angiotensin-Converting Enzyme 2; *covid-19; Humans; Peptidyl-Dipeptidase A/metabolism; RNA, Viral; SARS-CoV-2; ACE2-Fc; Adcc; Covid-19; antibody effector function; complement; coronavirus; neutralization
- Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- 35967361
- Publisher's Version
- https://doi.org/10.3389/fimmu.2022.889372
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2022.889372- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-08-19 09:30:39
Last Modified: 2022-08-19 09:47:00