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Therapeutic Potential of SARS-CoV-2-Specific Monoclonal Antibody CR3022

15 Pages Posted: 1 Jun 2020 Publication Status: Review Complete

See all articles by Caroline Atyeo

Caroline Atyeo

Ragon Institute of MGH, MIT and Harvard

Matthew D. Slein

Ragon Institute of MGH, MIT and Harvard

Stephanie Fischinger

Ragon Institute of MGH, MIT and Harvard

John Burke

Ragon Institute of MGH, MIT and Harvard

Alexandra Schӓfer

University of North Carolina (UNC) at Chapel Hill - Department of Epidemiology

Sarah R. Leist

University of North Carolina (UNC) at Chapel Hill - Department of Epidemiology

Anna Honko

Boston University - Department of Microbiology

Rebecca Johnson

Boston University - Department of Microbiology

Nadia Storm

Boston University - Department of Microbiology

Matthew Bernett

Xencor

Caitlyn Linde

SeromYx Systems

Todd Suscovich

SeromYx Systems

Anthony Griffiths

Boston University - Department of Microbiology

John R. Desjarlais

Xencor

Boris D. Juelg

Ragon Institute of MGH, MIT and Harvard

Jaap Goudsmit

Harvard University - Department of Epidemiology

Ralph Baric

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology

Galit Alter

Ragon Institute of MGH, MIT and Harvard

More...

Abstract

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

Suggested Citation

Atyeo, Caroline and Slein, Matthew D. and Fischinger, Stephanie and Burke, John and Schӓfer, Alexandra and Leist, Sarah R. and Honko, Anna and Johnson, Rebecca and Storm, Nadia and Bernett, Matthew and Linde, Caitlyn and Suscovich, Todd and Griffiths, Anthony and Desjarlais, John R. and Juelg, Boris D. and Goudsmit, Jaap and Baric, Ralph and Alter, Galit, Therapeutic Potential of SARS-CoV-2-Specific Monoclonal Antibody CR3022. Available at SSRN: https://ssrn.com/abstract=3612156 or http://dx.doi.org/10.2139/ssrn.3612156
This version of the paper has not been formally peer reviewed.

Caroline Atyeo

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Matthew D. Slein

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Stephanie Fischinger

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

John Burke

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Alexandra Schӓfer

University of North Carolina (UNC) at Chapel Hill - Department of Epidemiology

United States

Sarah R. Leist

University of North Carolina (UNC) at Chapel Hill - Department of Epidemiology ( email )

United States

Anna Honko

Boston University - Department of Microbiology

595 Commonwealth Avenue
Boston, MA 02215
United States

Rebecca Johnson

Boston University - Department of Microbiology

595 Commonwealth Avenue
Boston, MA 02215
United States

Nadia Storm

Boston University - Department of Microbiology

595 Commonwealth Avenue
Boston, MA 02215
United States

Caitlyn Linde

SeromYx Systems

Todd Suscovich

SeromYx Systems

Anthony Griffiths

Boston University - Department of Microbiology

595 Commonwealth Avenue
Boston, MA 02215
United States

Boris D. Juelg

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Jaap Goudsmit

Harvard University - Department of Epidemiology

655 Huntington Ave.
Boston, MA 02115
United States

Ralph Baric

University of North Carolina (UNC) at Chapel Hill - Department of Microbiology and Immunology

Chapel Hill, NC
United States

Galit Alter (Contact Author)

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

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