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

Authors :
Case JB
Rothlauf PW
Chen RE
Liu Z
Zhao H
Kim AS
Bloyet LM
Zeng Q
Tahan S
Droit L
Ilagan MXG
Tartell MA
Amarasinghe G
Henderson JP
Miersch S
Ustav M
Sidhu S
Virgin HW
Wang D
Ding S
Corti D
Theel ES
Fremont DH
Diamond MS
Whelan SPJ
Source :
SSRN [SSRN] 2020 May 27, pp. 3606354. Date of Electronic Publication: 2020 May 27.
Publication Year :
2020

Abstract

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-SARSCoV-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.<br />Competing Interests: COMPETING FINANCIAL INTERESTS 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.

Details

Language :
English
ISSN :
1556-5068
Database :
MEDLINE
Journal :
SSRN
Publication Type :
Academic Journal
Accession number :
32714117
Full Text :
https://doi.org/10.2139/ssrn.3606354