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Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy

Authors :
Yamin, Rachel
Jones, Andrew T.
Hoffmann, Hans-Heinrich
Schäfer, Alexandra
Kao, Kevin S.
Francis, Rebecca L.
Sheahan, Timothy P.
Baric, Ralph S.
Rice, Charles M.
Ravetch, Jeffrey V.
Bournazos, Stylianos
Source :
Nature. November 18, 2021, Vol. 599 Issue 7885, p465, 6 p.
Publication Year :
2021

Abstract

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease.sup.1-4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-19.sup.5. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-19.sup.6,7, we demonstrate that selective engagement of activating Fc[gamma] receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fc[gamma] receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fc[gamma] receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease. Optimization of monoclonal antibodies against SARS-CoV-2 for enhanced Fc-effector function increase their effectiveness for prevention and treatment of COVID-19 in multiple animal models of SARS-CoV-2 infection.<br />Author(s): Rachel Yamin [sup.1] , Andrew T. Jones [sup.1] , Hans-Heinrich Hoffmann [sup.2] , Alexandra Schäfer [sup.3] , Kevin S. Kao [sup.1] , Rebecca L. Francis [sup.1] , Timothy P. [...]

Details

Language :
English
ISSN :
00280836
Volume :
599
Issue :
7885
Database :
Gale General OneFile
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
edsgcl.682928428
Full Text :
https://doi.org/10.1038/s41586-021-04017-w