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

tetano

Editor, Senior Moderator
Nat Biotechnol


. 2020 Jul 23.
doi: 10.1038/s41587-020-0631-z. Online ahead of print.
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction


Chee Wah Tan[SUP] 1 [/SUP], Wan Ni Chia[SUP] 1 [/SUP], Xijian Qin[SUP] 2 [/SUP], Pei Liu[SUP] 2 [/SUP], Mark I-C Chen[SUP] 3 4 [/SUP], Charles Tiu[SUP] 1 [/SUP], Zhiliang Hu[SUP] 5 6 [/SUP], Vivian Chih-Wei Chen[SUP] 1 [/SUP], Barnaby E Young[SUP] 3 7 8 [/SUP], Wan Rong Sia[SUP] 1 [/SUP], Yee-Joo Tan[SUP] 9 10 [/SUP], Randy Foo[SUP] 1 [/SUP], Yongxiang Yi[SUP] 5 [/SUP], David C Lye[SUP] 3 7 8 11 [/SUP], Danielle E Anderson[SUP] 12 13 [/SUP], Lin-Fa Wang[SUP] 14 15 [/SUP]



Affiliations

Abstract

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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