Tweet
Cell Host Microbe
. 2020 Jul 3;S1931-3128(20)30362-0.
doi: 10.1016/j.chom.2020.06.021. Online ahead of print.
Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2
James Brett Case 1 , Paul W Rothlauf 2 , Rita E Chen 3 , Zhuoming Liu 4 , Haiyan Zhao 5 , Arthur S Kim 3 , Louis-Marie Bloyet 4 , Qiru Zeng 4 , Stephen Tahan 4 , Lindsay Droit 4 , Ma Xenia G Ilagan 6 , Michael A Tartell 2 , Gaya Amarasinghe 7 , Jeffrey P Henderson 1 , Shane Miersch 8 , Mart Ustav 8 , Sachdev Sidhu 8 , Herbert W Virgin 9 , David Wang 10 , Siyuan Ding 4 , Davide Corti 11 , Elitza S Theel 12 , Daved H Fremont 13 , Michael S Diamond 14 , Sean P J Whelan 15
Affiliations
- PMID: 32735849
- DOI: 10.1016/j.chom.2020.06.021
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.
Keywords: ACE2; COVID19; SARS-CoV-2; VSV; antibody; coronavirus; neutralizing; serum; surrogate assay.