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

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Source: https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30362-0


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
Paul W. Rothlauf ∗
Rita E. Chen
Daved H. Fremont
Michael S. Diamond
Sean P.J. Whelan #
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Published:July 01, 2020DOI:https://doi.org/10.1016/j.chom.2020.06.021

Highlights

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Vesicular stomatitis virus encoding the SARS-CoV-2 spike replicates to high titers
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Virus propagation is enhanced by a truncation in the cytoplasmic tail of the spike
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Neutralization can be assessed by BSL2 and BSL3 high-throughput assays
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SARS-CoV-2 and VSV-SARS-CoV-2-based neutralization assays correlate

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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Source: https://medicine.wustl.edu/news/lab-made-virus-mimics-covid-19-virus/

News Release
Lab-made virus mimics COVID-19 virus
Is safer to work with, can aid efforts to find drugs, vaccines
by Tamara Bhandari•July 20, 2020



Paul Rothlauf, a visiting scientist at Washington University School of Medicine in St. Louis, works with a lab-made virus that infects cells and interacts with antibodies just like the COVID-19 virus, but lacks the ability to cause severe disease. This safer virus makes it possible for scientists who do not have access to high-level biosafety facilities to join the effort to find drugs or vaccines for COVID-19.

Airborne and potentially deadly, the virus that causes COVID-19 can only be studied safely under high-level biosafety conditions. Scientists handling the infectious virus must wear full-body biohazard suits with pressurized respirators, and work inside laboratories with multiple containment levels and specialized ventilation systems. While necessary to protect laboratory workers, these safety precautions slow down efforts to find drugs and vaccines for COVID-19 since many scientists lack access to the required biosafety facilities.

To help remedy that, researchers at Washington University School of Medicine in St. Louis have developed a hybrid virus that will enable more scientists to enter the fight against the pandemic. The researchers genetically modified a mild virus by swapping one of its genes for one from SARS-CoV-2, the virus that causes COVID-19. The resulting hybrid virus infects cells and is recognized by antibodies just like SARS-CoV-2, but can be handled under ordinary laboratory safety conditions....