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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| Veröffentlicht in: | Nature biotechnology Jg. 38; H. 9; S. 1073 - 1078 |
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| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
Nature Publishing Group
01.09.2020
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| ISSN: | 1087-0156, 1546-1696, 1546-1696 |
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| 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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| AbstractList | 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. 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 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 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. |
| Author | Liu, Pei Qin, Xijian Chia, Wan Ni Tiu, Charles Young, Barnaby E Yi, Yongxiang Hu, Zhiliang Wang, Lin-Fa Chen, Mark I-C Tan, Yee-Joo Tan, Chee Wah Foo, Randy Anderson, Danielle E Chen, Vivian Chih-Wei Lye, David C Sia, Wan Rong |
| Author_xml | – sequence: 1 givenname: Chee Wah surname: Tan fullname: Tan, Chee Wah organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 2 givenname: Wan Ni surname: Chia fullname: Chia, Wan Ni organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 3 givenname: Xijian surname: Qin fullname: Qin, Xijian organization: GenScript Biotech, Nanjing, China – sequence: 4 givenname: Pei surname: Liu fullname: Liu, Pei organization: GenScript Biotech, Nanjing, China – sequence: 5 givenname: Mark I-C surname: Chen fullname: Chen, Mark I-C organization: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore – sequence: 6 givenname: Charles surname: Tiu fullname: Tiu, Charles organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 7 givenname: Zhiliang surname: Hu fullname: Hu, Zhiliang organization: Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China – sequence: 8 givenname: Vivian Chih-Wei orcidid: 0000-0001-8757-0644 surname: Chen fullname: Chen, Vivian Chih-Wei organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 9 givenname: Barnaby E orcidid: 0000-0003-1010-2230 surname: Young fullname: Young, Barnaby E organization: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore – sequence: 10 givenname: Wan Rong orcidid: 0000-0003-2694-4192 surname: Sia fullname: Sia, Wan Rong organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 11 givenname: Yee-Joo surname: Tan fullname: Tan, Yee-Joo organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore – sequence: 12 givenname: Randy surname: Foo fullname: Foo, Randy organization: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore – sequence: 13 givenname: Yongxiang surname: Yi fullname: Yi, Yongxiang organization: Nanjing Infectious Disease Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China – sequence: 14 givenname: David C surname: Lye fullname: Lye, David C organization: Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore – sequence: 15 givenname: Danielle E orcidid: 0000-0003-4791-5024 surname: Anderson fullname: Anderson, Danielle E email: Danielle.anderson@duke-nus.edu.sg, Danielle.anderson@duke-nus.edu.sg organization: SingHealth Duke-NUS Global Health Institute, Singapore, Singapore. Danielle.anderson@duke-nus.edu.sg – sequence: 16 givenname: Lin-Fa orcidid: 0000-0003-2752-0535 surname: Wang fullname: Wang, Lin-Fa email: linfa.wang@duke-nus.edu.sg, linfa.wang@duke-nus.edu.sg organization: SingHealth Duke-NUS Global Health Institute, Singapore, Singapore. linfa.wang@duke-nus.edu.sg |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32704169$$D View this record in MEDLINE/PubMed |
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| Snippet | 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... |
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| SubjectTerms | 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 |
| Title | A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction |
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