Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo-Reference-Cited by-同舟云学术

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

Published:2020-11-19 Issue:3 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Schäfer Alexandra¹^ORCID,Muecksch Frauke²^ORCID,Lorenzi Julio C.C.³^ORCID,Leist Sarah R.¹^ORCID,Cipolla Melissa³^ORCID,Bournazos Stylianos⁴^ORCID,Schmidt Fabian²^ORCID,Maison Rachel M.⁵^ORCID,Gazumyan Anna³^ORCID,Martinez David R.¹^ORCID,Baric Ralph S.¹⁶^ORCID,Robbiani Davide F.³⁷^ORCID,Hatziioannou Theodora²^ORCID,Ravetch Jeffrey V.⁴^ORCID,Bieniasz Paul D.²⁸^ORCID,Bowen Richard A.⁵^ORCID,Nussenzweig Michel C.³⁸^ORCID,Sheahan Timothy P.¹^ORCID

Affiliation:

1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC

2. Laboratory of Retrovirology, The Rockefeller University, New York, NY

3. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY

4. Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY

5. Laboratory of Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO

6. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC

7. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland

8. Howard Hughes Medical Institute, The Rockefeller University, New York, NY

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.

Funder

George Mason University

National Institute of Allergy and Infectious Diseases

Antiviral Drug Discovery and Development Center

Howard Hughes Medical Institute

The Rockefeller University

North Carolina Policy Collaboratory

University of North Carolina at Chapel Hill

North Carolina Coronavirus Relief Fund

North Carolina General Assembly

Publisher

Rockefeller University Press