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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.
Cell Host Microbe. 2020 Sep 09; 28(3):475-485.e5.CH

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.

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Authors+Show Affiliations

Case JB
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Rothlauf PW
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.
Chen RE
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Liu Z
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Zhao H
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Kim AS
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Bloyet LM
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Zeng Q
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Tahan S
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Droit L
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Ilagan MXG
Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Tartell MA
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.
Amarasinghe G
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Henderson JP
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Miersch S
The Donnelly Centre, University of Toronto, Toronto, Canada.
Ustav M
The Donnelly Centre, University of Toronto, Toronto, Canada.
Sidhu S
The Donnelly Centre, University of Toronto, Toronto, Canada.
Virgin HW
Vir Biotechnology, San Francisco, CA, USA.
Wang D
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Ding S
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Corti D
Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., CH-6500, Bellinzona, Switzerland.
Theel ES
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Fremont DH
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
Diamond MS
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: diamond@wusm.wustl.edu.
Whelan SPJ
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: spjwhelan@wustl.edu.

MeSH

Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralBetacoronavirusCOVID-19Chlorocebus aethiopsCoronavirus InfectionsGreen Fluorescent ProteinsHost Microbial InteractionsHumansImmunization, PassiveNeutralization TestsPandemicsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Spike Glycoprotein, CoronavirusVero CellsVesicular stomatitis Indiana virusVirus InternalizationVirus ReplicationCOVID-19 Serotherapy

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32735849

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." Cell Host & Microbe, vol. 28, no. 3, 2020, pp. 475-485.e5.
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. Cell Host Microbe. 2020;28(3):475-485.e5.
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. Cell Host & Microbe, 28(3), 475-e5. https://doi.org/10.1016/j.chom.2020.06.021
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. Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5. PubMed PMID: 32735849.
* 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 - 2020/07/03/ PY - 2020/5/17/received PY - 2020/6/18/revised PY - 2020/6/24/accepted PY - 2020/8/1/pubmed PY - 2020/9/22/medline PY - 2020/8/1/entrez KW - ACE2 KW - COVID19 KW - SARS-CoV-2 KW - VSV KW - antibody KW - coronavirus KW - neutralizing KW - serum KW - surrogate assay SP - 475 EP - 485.e5 JF - Cell host & microbe JO - Cell Host Microbe VL - 28 IS - 3 N2 - 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. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/32735849/Neutralizing_Antibody_and_Soluble_ACE2_Inhibition_of_a_Replication_Competent_VSV_SARS_CoV_2_and_a_Clinical_Isolate_of_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -