Cited by 410SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesSARS-CoV-2 detection and testing

Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2

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Case, James Brett, Rothlauf, Paul W., Chen, Rita E., Liu, Zhuoming, Zhao, Haiyan, Kim, Arthur S., Bloyet, Louis-Marie, Zeng, Qiru +17 more·2020·Cell Host & Microbe

Published version of a preprint

Abstract

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, which engages with host ACE2 receptor for entry. Using an infectious molecular clone of vesicular stomatitis virus (VSV) expressing eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput-imaging-based neutralization assay at biosafety level 2. We also developed a focus-reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. Comparing the neutralizing activities of various antibodies and ACE2-Fc soluble decoy protein in both assays revealed a high degree of concordance. These assays will help define correlates of protection for antibody-based countermeasures and vaccines against SARS-CoV-2. Additionally, replication-competent VSV-eGFP-SARS-CoV-2 provides a tool for testing inhibitors of SARS-CoV-2 mediated entry under reduced biosafety containment.

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  • SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2).

    “SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2)1,28.”
  • The pseudovirus-neutralization test (pVNT) has been shown to be in close concordance with live SARS-CoV-2-neutralization assays.

    “a pseudovirus-neutralization test (pVNT) that has been shown to be in close concordance with live SARS-CoV-2–neutralization assays (17, 18)”
  • The study used two orthogonal test systems: a pseudovirus-neutralization test and a live SARS-CoV-2-neutralization test.

    “we used two orthogonal test systems: a pseudovirus-neutralization test (pVNT) that has been shown to be in close concordance with live SARS-CoV-2–neutralization assays (17, 18), as well as a live SARS-CoV-2–neutralization test (VNT).”

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Authors
Case, J. B., Rothlauf, P. W., Chen, R. E., Liu, Z., Zhao, H., Kim, A. S., Bloyet, L.-M., Zeng, Q., Tahan, S., Droit, L., Ilagan, M. X. G., Tartell, M. A., Amarasinghe, G., Henderson, J. P., Miersch, S., Ustav, M., Sidhu, S., Virgin, H. W., Wang, D., Ding, S., Corti, D., Theel, E. S., Fremont, D. H., Diamond, M. S., & Whelan, S. P. J.
Affiliations
  • Washington University in St. Louis (US)
  • Harvard University (US)
  • University of Toronto (CA)
  • VIR Biotechnology (United States) (US)
  • Vir Biotechnology (Switzerland) (CH)
  • Mayo Clinic (US)
Corresponding author
  • Diamond, Michael S.
  • Whelan, Sean P.J.
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2020-09
Volume
28
Issue
3
Pages
475-485.e5
ISSN
1931-3128 (ISSN-L)
OpenAlex
W3040017923
Cited by
410
References
92
Citations by year
2026: 25 · 2025: 25 · 2024: 40 · 2023: 47 · 2022: 99 · 2021: 127 · 2020: 46
FWCI
10.46
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • SSRN Electronic Journal (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • HAL (submittedVersion)
Funders
  • Helen Hay Whitney Foundation (MA104)
  • Washington University in St. Louis
  • Washington University School of Medicine in St. Louis
  • National Institutes of Health (75N93019C00062, HHSN272201700060C, R01 AI127828, R37 AI059371, U01 AI151810)
  • Vir Biotechnology
  • Eli Lilly and Company
  • Defense Advanced Research Projects Agency (HR001117S0019)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords
SARS-CoV-2, neutralizing antibodies, soluble ACE2, spike protein, focus reduction neutralization test, correlates of protection, vaccine development, viral entry inhibitors, biosafety level 2, biosafety level 3

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