Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo
- Schäfer, Alexandra ORCID Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Muecksch, Frauke ORCID Laboratory of Retrovirology, The Rockefeller University, New York, NY
- Lorenzi, Julio C.C. ORCID Laboratory of Molecular Immunology, The Rockefeller University, New York, NY
- Leist, Sarah R. ORCID Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Cipolla, Melissa ORCID Laboratory of Molecular Immunology, The Rockefeller University, New York, NY
- Bournazos, Stylianos ORCID Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY
- Schmidt, Fabian ORCID Laboratory of Retrovirology, The Rockefeller University, New York, NY
- Maison, Rachel M. ORCID Laboratory of Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO
- Gazumyan, Anna ORCID Laboratory of Molecular Immunology, The Rockefeller University, New York, NY
- Martinez, David R. ORCID Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Baric, Ralph S. ORCID Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Robbiani, Davide F. ORCID Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
- Hatziioannou, Theodora ORCID Laboratory of Retrovirology, The Rockefeller University, New York, NY
- Ravetch, Jeffrey V. ORCID Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY
- Bieniasz, Paul D. ORCID Howard Hughes Medical Institute, The Rockefeller University, New York, NY
- Bowen, Richard A. ORCID Laboratory of Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO
- Nussenzweig, Michel C. ORCID Howard Hughes Medical Institute, The Rockefeller University, New York, NY
- Sheahan, Timothy P. ORCID Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
- 2020-11-19
Published in:
- Journal of Experimental Medicine. - Rockefeller University Press. - 2020, vol. 218, no. 3
English
SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1084/jem.20201993
- ISSN 0022-1007
- Persistent URL
- https://folia.unifr.ch/global/documents/235204
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