期刊
NATURE
卷 599, 期 7885, 页码 465-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-04017-w
关键词
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资金
- NIH Core Grant [P30CA008748]
- National Institute of Allergy and Infectious Diseases [R01AI137276, R01AI157155, U19AI111825, R01AI145870]
- Bill and Melinda Gates Foundation [INV023152]
- G. Harold and Leila Y. Mathers Charitable Foundation
- Bawd Foundation
- Fast Grants, a part of Emergent Ventures at the Mercatus Center, George Mason University
- Rockefeller University
- Vir Biotechnology
Monoclonal antibodies with optimized Fc domains show superior potency in preventing and treating COVID-19 in animal disease models, reducing the dose required for protection against SARS-CoV-2 challenge and for treating pre-infected animals. Selective engagement of activating Fc receptors results in improved efficacy, highlighting the importance of Fc receptor pathways in driving antibody-mediated antiviral immunity. These findings have implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function against COVID-19.
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(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(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(6,7), we demonstrate that selective engagement of activating Fc. 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. receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fc. 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.
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