Therapeutic Potential of SARS-CoV-2-Specific Monoclonal Antibody CR3022
15 Pages Posted: 1 Jun 2020 Publication Status: Review CompleteMore...
The spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics or vaccines, has paralyzed the globe. While significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc-interactions may be vital to eliminate the virus. However, Fc-engineering efforts have largely been blind, using limited data to select Fc-modifications. To explore the role of Fc-activity in SARS-CoV-2 immunity, the functional potential of a cross-SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc-variants, enhanced disease was observed after administration of wildtype IgG. Conversely, the functionally enhanced Fc-variant provided protection when administered therapeutically. Surprisingly, the Fc-silenced variant showed significant protection. These data point to the need for strategic Fc-engineering for the prevention and treatment of SARS-CoV-2 infection.
Funding: We acknowledge support from the Ragon Institute of MGH, MIT, the Massachusetts Consortium on Pathogen Readiness (MassCPR), and the Bill & Melinda Gates Foundation (235730).
Conflict of Interest: Galit Alter is a founder of SeromYx Systems. All other authors declare no conflicts of interest.
Keywords: SARS-CoV-2, antibody effector function, immunity, Fc function, CR3022
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