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

James Brett Case, Paul W. Rothlauf, Rita E. Chen, Zhuoming Liu, Haiyan Zhao, Arthur S. Kim, Louis Marie Bloyet, Qiru Zeng, Stephen Tahan, Lindsay Droit, Ma Xenia G. Ilagan, Michael A. Tartell, Gaya Amarasinghe, Jeffrey P. Henderson, Shane Miersch, Mart Ustav, Sachdev Sidhu, Herbert W. Virgin, David Wang, Siyuan DingDavide Corti, Elitza S. Theel, Daved H. Fremont, Michael S. Diamond, Sean P.J. Whelan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)475-485.e5
JournalCell Host and Microbe
Volume28
Issue number3
DOIs
StatePublished - Sep 9 2020

Keywords

  • ACE2
  • COVID19
  • SARS-CoV-2
  • VSV
  • antibody
  • coronavirus
  • neutralizing
  • serum
  • surrogate assay

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