Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2

• Published in: Cell host & microbe Vol. 28; no. 3; pp. 475 - 485.e5
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.09.2020
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; antibody; Betacoronavirus - genetics; Betacoronavirus - immunology; Betacoronavirus - physiology; Chlorocebus aethiops; coronavirus; Coronavirus Infections - genetics; Coronavirus Infections - immunology; Coronavirus Infections - therapy; Coronavirus Infections - virology; COVID-19; COVID-19 Serotherapy; COVID19; Green Fluorescent Proteins - genetics; Host Microbial Interactions - immunology; Humans; Immunization, Passive; Life Sciences; Microbiology and Parasitology; Neutralization Tests; neutralizing; Pandemics; Peptidyl-Dipeptidase A - immunology; Pneumonia, Viral - immunology; Pneumonia, Viral - therapy; Pneumonia, Viral - virology; Resource; SARS-CoV-2; serum; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; surrogate assay; Vero Cells; Vesicular stomatitis Indiana virus - genetics; Vesicular stomatitis Indiana virus - immunology; Virology; Virus Internalization; Virus Replication; VSV; ACE2; SARS-CoV-2; COVID19; antibody; VSV; coronavirus; neutralizing; serum; surrogate assay; Vesicular stomatitis virus; Neutralizing antibodies
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2020.06.021

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. [Display omitted] •Vesicular stomatitis virus encoding the SARS-CoV-2 spike replicates to high titers•Virus propagation is enhanced by a truncation in the cytoplasmic tail of the spike•Neutralization can be assessed by BSL2 and BSL3 high-throughput assays•SARS-CoV-2- and VSV-SARS-CoV-2-based neutralization assays correlate Case, Rothlauf et al. generate a replication-competent vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike and compare the neutralizing activity of antibodies with VSV-SARS-CoV-2 to fully infectious SARS-CoV-2. They show that VSV-SARS-CoV-2 is a useful BSL2 surrogate virus, as neutralization profiles strongly correlate with focus-reduction neutralization tests using SARS-CoV-2.