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Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.
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.
  • Yamin R; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
  • Jones AT; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
  • Hoffmann HH; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kao KS; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
  • Francis RL; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
  • Sheahan TP; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Rice CM; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Ravetch JV; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • Bournazos S; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA. ravetch@rockefeller.edu.
Nature ; 599(7885): 465-470, 2021 11.
Article in English | MEDLINE | ID: covidwho-1428880
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 disease1-4. 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-195. 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-196,7, we demonstrate that selective engagement of activating Fcγ 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 Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin Fc Fragments / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment / Antibodies, Monoclonal Type of study: Experimental Studies / Prognostic study Limits: Animals / Female / Humans / Male Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-021-04017-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin Fc Fragments / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment / Antibodies, Monoclonal Type of study: Experimental Studies / Prognostic study Limits: Animals / Female / Humans / Male Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-021-04017-w