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

The Journal of Experimental Medicine
Alexandra SchäferTimothy P Sheahan

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.

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Citations

Jan 27, 2021·Cell·Alessandro Sette, Shane Crotty
Jan 19, 2021·Nature·Christian GaeblerMichel C Nussenzweig
Jan 8, 2021·Clinical Pharmacology and Therapeutics·Alan S Perelson, Ruian Ke
Feb 11, 2021·Nature·Zijun WangMichel C Nussenzweig
Mar 12, 2021·Cell Host & Microbe·Jérémie Prévost, Andrés Finzi
Apr 3, 2021·Cell Host & Microbe·Venkata Viswanadh EdaraMehul S Suthar
Mar 24, 2021·Expert Opinion on Therapeutic Targets·Simone I Richardson, Penny L Moore
Apr 5, 2021·EBioMedicine·Martin S WinklerMarcin F Osuchowski
Apr 22, 2021·MBio·Harini NatarajanMargaret E Ackerman
May 1, 2021·Nature Reviews. Immunology·Deborah CromerMiles P Davenport
Apr 28, 2021·Current Opinion in Virology·Chung-Young Lee, Anice C Lowen
May 12, 2021·Proteins·Wenyang Jing, Erik Procko
May 18, 2021·Cell Reports Medicine·Wen Shi LeeStephen J Kent
Jun 5, 2021·Cell·Davide CortiDavid Veesler
Jun 1, 2021·Cell Reports Medicine·Andrea R ShiakolasIvelin S Georgiev
Jun 14, 2021·Biochemical and Biophysical Research Communications·Dong-Kyun RyuSoo-Young Lee
Jul 9, 2021·Frontiers in Immunology·Christina WoopenTjalf Ziemssen

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Methods Mentioned

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