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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James Brett Case

Paul W Rothlauf

Rita E. Chen

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Zhuoming Liu

Haiyan Zhao

Published 4 Projects

Microbiology

Arthur S Kim

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Microbiology

Louis-Marie Bloyet

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Immunology Microbiology

Qiru Zeng

Published 4 Projects

Microbiology

Stephen Tahan

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Microbiology

Lindsay Droit

Published 2 Projects

Microbiology

Ma. Xenia G. Ilagan

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Microbiology

Michael A Tartell

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Microbiology

Gaya Amarasinghe

Jeffrey P Henderson

Published 1 Project

Microbiology

Shane Miersch

Mart Ustav

Sachdev S Sidhu

Herbert W Virgin

Published 4 Projects

Immunology Microbiology

David Wang

Published 2 Projects

Microbiology

Siyuan Ding

Published 4 Projects

Microbiology

Davide Corti

Published 4 Projects

Immunology Microbiology

Elitza S Theel

Published 2 Projects

Microbiology

Daved H Fremont

Published 4 Projects

Immunology Microbiology

Michael Diamond

Sean P. J. Whelan

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Antibody-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. ### Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and on the Scientific Advisory Board of Moderna. D.C. and H.W.V. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. S.P.J.W. and P.W.R. have filed a disclosure with Washington University for the recombinant VSV.

Microbiology
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