Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2.

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

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.