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

Author:

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

ABSTRACTAntibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly disrupt epidemic transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, yet there is no consensus as to which assay should be used for such measurements. Using an infectious molecular clone of vesicular stomatitis virus (VSV) that expresses 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. We compared the neutralizing activities of monoclonal and polyclonal antibody preparations, as well as ACE2-Fc soluble decoy protein in both assays and find an exceptionally high degree of concordance. The two assays will help define correlates of protection for antibody-based countermeasures including therapeutic antibodies, immune γ-globulin or plasma preparations, and vaccines against SARS-CoV-2. Replication-competent VSV-eGFP-SARS-CoV-2 provides a rapid assay for testing inhibitors of SARS-CoV-2 mediated entry that can be performed in 7.5 hours under reduced biosafety containment.

Publisher

Cold Spring Harbor Laboratory

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