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- Title
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction.
- 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
- 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. A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus.
- Publication
Nature Biotechnology, 2020, Vol 38, Issue 9, p1073
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/s41587-020-0631-z