Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy

Rachel Yamin, Andrew T. Jones, Hans-Heinrich Hoffmann, Alexandra Schäfer, Kevin S. Kao, Rebecca L. Francis, Timothy P. Sheahan, Ralph S. Baric, Charles M. Rice, Jeffrey V. Ravetch () and Stylianos Bournazos ()
Additional contact information
Rachel Yamin: The Rockefeller University
Andrew T. Jones: The Rockefeller University
Hans-Heinrich Hoffmann: The Rockefeller University
Alexandra Schäfer: University of North Carolina at Chapel Hill
Kevin S. Kao: The Rockefeller University
Rebecca L. Francis: The Rockefeller University
Timothy P. Sheahan: University of North Carolina at Chapel Hill
Ralph S. Baric: University of North Carolina at Chapel Hill
Charles M. Rice: The Rockefeller University
Jeffrey V. Ravetch: The Rockefeller University
Stylianos Bournazos: The Rockefeller University

Nature, 2021, vol. 599, issue 7885, 465-470

Abstract: Abstract Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1–4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-195. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-196,7, we demonstrate that selective engagement of activating Fcγ receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04017-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:599:y:2021:i:7885:d:10.1038_s41586-021-04017-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-04017-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().