Fc-independent protection from sars-cov-2 infection by recombinant human monoclonal antibodies

Tal Noy-Porat, Avishay Edri, Ron Alcalay, Efi Makdasi, David Gur, Moshe Aftalion, Yentl Evgy, Adi Beth-Din, Yinon Levy, Eyal Epstein, Olga Radinsky, Ayelet Zauberman, Shirley Lazar, Shmuel Yitzhaki, Hadar Marcus, Angel Porgador, Ronit Rosenfeld, Ohad Mazor

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.

Original languageEnglish
Article number45
Issue number4
StatePublished - 1 Dec 2021


  • A-glycosylated
  • Fragment crystallizable (Fc)
  • K18-hACE2
  • Monoclonal antibodies (mAbs)
  • SARS-CoV-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Drug Discovery


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