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

Type Journal Article Author Chee Wah Tan Author Wan Ni Chia Author Xijian Qin Author Pei Liu Author Mark I.-C. Chen Author Charles Tiu Author Zhiliang Hu Author Vivian Chih-Wei Chen Author Barnaby E. Young Author Wan Rong Sia Author Yee-Joo Tan Author Randy Foo Author Yongxiang Yi Author David C. Lye Author Danielle E. Anderson Author Lin-Fa Wang URL https://www.nature.com/articles/s41587-020-0631-z Rights 2020 The Author(s), under exclusive licence to Springer Nature America, Inc. Volume 38 Issue 9 Pages 1073-1078 Publication Nature Biotechnology ISSN 1546-1696 Date 23/07/2020 Extra Number: 9 Publisher: Nature Publishing Group DOI 10.1038/s41587-020-0631-z Library Catalog www.nature.com Language en 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.