期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20201993
关键词
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资金
- George Mason University
- National Institute of Allergy and Infectious Diseases [1U19AI142759, P01-AI138398-S1, 2U1 9AI111825, R01AI137276, U19AI111825]
- North Carolina Policy Collaboratory at University of North Carolina at Chapel Hill
- North Carolina Coronavirus Relief Fund
The study shows that combined use of hu-mAbs is effective for prevention and therapy of SARS-CoV-2 infection, but in vivo protection is influenced by intact effector function.
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.
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