A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the...

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Bibliographic Details
Published in:Nature biotechnology Vol. 38; no. 9; pp. 1073 - 1078
Main Authors: Tan, Chee Wah, Chia, Wan Ni, Qin, Xijian, Liu, Pei, Chen, Mark I-C, Tiu, Charles, Hu, Zhiliang, Chen, Vivian Chih-Wei, Young, Barnaby E, Sia, Wan Rong, Tan, Yee-Joo, Foo, Randy, Yi, Yongxiang, Lye, David C, Anderson, Danielle E, Wang, Lin-Fa
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.09.2020
Subjects:
ACE2
Angiotensin
Angiotensin-Converting Enzyme 2
Antibodies
Antibodies - immunology
Antibodies - pharmacology
Betacoronavirus - genetics
Betacoronavirus - pathogenicity
Binding
Biosafety
Clinical trials
Containment
Coronavirus Infections - genetics
Coronavirus Infections - immunology
Coronavirus Infections - pathology
Coronavirus Infections - virology
Coronaviruses
COVID-19
Enzymes
Herd immunity
Humans
Humoral immunity
Neutralization
Neutralization Tests
Neutralizing
Pandemics
Peptidyl-dipeptidase A
Peptidyl-Dipeptidase A - genetics
Pneumonia, Viral - genetics
Pneumonia, Viral - immunology
Pneumonia, Viral - pathology
Pneumonia, Viral - virology
Protein Interaction Domains and Motifs - genetics
Proteins
Receptors
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - genetics
Spike protein
Vaccination
Vaccine efficacy
Vaccines
Viral diseases
Viruses
ISSN:1087-0156, 1546-1696, 1546-1696
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Summary:A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.
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ISSN:1087-0156
1546-1696
1546-1696
DOI:10.1038/s41587-020-0631-z