Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding-Reference-Cited by-同舟云学术

Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding

Published:2020-10-28 Issue:5 Volume:5 Page:
ISSN:2379-5042
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language:en
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Author:

Byrnes James R.¹^ORCID,Zhou Xin X.¹^ORCID,Lui Irene¹^ORCID,Elledge Susanna K.¹^ORCID,Glasgow Jeff E.¹^ORCID,Lim Shion A.¹^ORCID,Loudermilk Rita P.²³^ORCID,Chiu Charles Y.⁴⁵^ORCID,Wang Taia T.⁶⁷⁸^ORCID,Wilson Michael R.²³^ORCID,Leung Kevin K.¹^ORCID,Wells James A.¹⁶⁹^ORCID

Affiliation:

1. Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA

2. Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA

3. Department of Neurology, University of California, San Francisco, San Francisco, California, USA

4. Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA

5. Department of Medicine, University of California, San Francisco, San Francisco, California, USA

6. Chan Zuckerberg Biohub, San Francisco, California, USA

7. Department of Medicine, Stanford University Medical School, Stanford, California, USA

8. Department of Microbiology and Immunology, Stanford University Medical School, Stanford, California, USA

9. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA

Abstract

With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.

Funder

Charles and Helen Schwab Foundation

Rachleff Family Endowment

CEND COVID Catalyst Fund

Harry and Dianna Hind Endowed Professorship in Pharmaceutical Sciences

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

HHS | NIH | National Heart, Lung, and Blood Institute

Helen Hay Whitney Foundation

Chan Zuckerberg Initiative

Fast Grants