Publications & Reports

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

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
Immune therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia.


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 FcgammaRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcgammaR 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 FcgammaRIIIa. 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.

Link to publisher’s web site


  • Journal: Frontiers in immunology
  • Published: 28/07/2022
  • Volume: 13
  • Pagination: 889372