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

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Schäfer, A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Muecksch, F.
    • Other Affiliation: Rockefeller University
  • Lorenzi, J.C.C.
    • Other Affiliation: Rockefeller University
  • Leist, S.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Cipolla, M.
    • Other Affiliation: Rockefeller University
  • Bournazos, S.
    • Other Affiliation: Rockefeller University
  • Schmidt, F.
    • Other Affiliation: Rockefeller University
  • Maison, R.M.
    • Other Affiliation: Colorado State University
  • Gazumyan, A.
    • Other Affiliation: Rockefeller University
  • Martinez, D.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Baric, R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Robbiani, D.F.
    • Other Affiliation: Rockefeller University
  • Hatziioannou, T.
    • Other Affiliation: Rockefeller University
  • Ravetch, J.V.
    • Other Affiliation: Rockefeller University
  • Bieniasz, P.D.
    • Other Affiliation: Rockefeller University
  • Bowen, R.A.
    • Other Affiliation: Colorado State University
  • Nussenzweig, M.C.
    • Other Affiliation: Rockefeller University
  • Sheahan, T.P.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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.
Date of publication
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Journal of Experimental Medicine
Journal volume
  • 218
Journal issue
  • 3
Language
  • English
ISSN
  • 0022-1007

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details Antibody_potency_effector_function_and_combinati.pdf 2020-12-02 Public Download