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Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

2020; Rockefeller University Press; Volume: 218; Issue: 3 Linguagem: Inglês

10.1084/jem.20201993

1540-9538

Alexandra Schäfer, Frauke Muecksch, Julio C. C. Lorenzi, Sarah R. Leist, Melissa Cipolla, Stylianos Bournazos, Fabian Schmidt, Rachel M. Maison, Anna Gazumyan, David R. Martinez, Ralph S. Baric, Davide F. Robbiani, Théodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Richard A. Bowen, Michel C. Nussenzweig, Timothy P. Sheahan,

SARS-CoV-2 detection and testing

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.