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 | Chen, Rita | Liu, Zhuoming | Zhao, Haiyan | Kim, Arthur | Bloyet, Louis-Marie | Zeng, Qiru | Tahan, Stephen | Droit, Lindsay | Ilagan, Ma. Xenia G. | Tartell, Michael | Amarasinghe, Gaya | Henderson, Jeffrey | Miersch, Shane | Ustav, Mart | Sidhu, Sachdev | Virgin, Herbert | Wang, David | Ding, Siyuan | Corti, Davide | Theel, Elitza | Fremont, Daved | Diamond, Michael | Whelan, Sean P.J.

Edité par CCSD -

International audience. 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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