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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.
bioRxiv. 2020 May 18B

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-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.

Authors

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Pub Type(s)

Preprint

Language

eng

PubMed ID

32511401

Citation

Case, James Brett, et al. "Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2." BioRxiv : the Preprint Server for Biology, 2020.
Case JB, Rothlauf PW, Chen RE, et al. Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. bioRxiv. 2020.
Case, J. B., Rothlauf, P. W., Chen, R. E., Liu, Z., Zhao, H., Kim, A. S., Bloyet, L. M., Zeng, Q., Tahan, S., Droit, L., Ilagan, M. X. G., Tartell, M. A., Amarasinghe, G., Henderson, J. P., Miersch, S., Ustav, M., Sidhu, S., Virgin, H. W., Wang, D., ... Whelan, S. P. J. (2020). Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2020.05.18.102038
Case JB, et al. Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2. bioRxiv. 2020 May 18; PubMed PMID: 32511401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. AU - Case,James Brett, AU - Rothlauf,Paul W, AU - Chen,Rita E, AU - Liu,Zhuoming, AU - Zhao,Haiyan, AU - Kim,Arthur S, AU - Bloyet,Louis-Marie, AU - Zeng,Qiru, AU - Tahan,Stephen, AU - Droit,Lindsay, AU - Ilagan,Ma Xenia G, AU - Tartell,Michael A, AU - Amarasinghe,Gaya, AU - Henderson,Jeffrey P, AU - Miersch,Shane, AU - Ustav,Mart, AU - Sidhu,Sachdev, AU - Virgin,Herbert W, AU - Wang,David, AU - Ding,Siyuan, AU - Corti,Davide, AU - Theel,Elitza S, AU - Fremont,Daved H, AU - Diamond,Michael S, AU - Whelan,Sean P J, Y1 - 2020/05/18/ PY - 2020/6/9/entrez PY - 2020/6/9/pubmed PY - 2020/6/9/medline JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - 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. UR - https://www.unboundmedicine.com/medline/citation/32511401/Neutralizing_antibody_and_soluble_ACE2_inhibition_of_a_replication_competent_VSV_SARS_CoV_2_and_a_clinical_isolate_of_SARS_CoV_2_ L2 - https://doi.org/10.1101/2020.05.18.102038 DB - PRIME DP - Unbound Medicine ER -
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