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

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, Theodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Richard A. Bowen, Michel C. Nussenzweig, Timothy P. Sheahan

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

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.
Original languageEnglish (US)
JournalJournal of Experimental Medicine
Volume218
Issue number3
DOIs
StatePublished - Jan 1 2020
Externally publishedYes

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Generated from Scopus record by KAUST IRTS on 2023-02-15

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