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
Hauptverfasser: 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
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.
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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