A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

M Eugenia Dieterle; Denise Haslwanter; Robert H Bortz 3rd; Ariel S Wirchnianski; Gorka Lasso; Olivia Vergnolle; Shawn A Abbasi; J Maximilian Fels; Ethan Laudermilch; Catalina Florez; Amanda Mengotto; Duncan Kimmel; Ryan J Malonis; George Georgiev; Jose Quiroz; Jason Barnhill; Liise-Anne Pirofski; Johanna P Daily; John M Dye; Jonathan R Lai; Andrew S Herbert; Kartik Chandran; Rohit K Jangra

doi:10.1016/j.chom.2020.06.020

A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

Cell Host Microbe. 2020 Sep 9;28(3):486-496.e6. doi: 10.1016/j.chom.2020.06.020. Epub 2020 Jul 3.

Authors

M Eugenia Dieterle¹, Denise Haslwanter¹, Robert H Bortz 3rd¹, Ariel S Wirchnianski², Gorka Lasso¹, Olivia Vergnolle³, Shawn A Abbasi⁴, J Maximilian Fels¹, Ethan Laudermilch¹, Catalina Florez⁵, Amanda Mengotto⁶, Duncan Kimmel⁶, Ryan J Malonis³, George Georgiev³, Jose Quiroz⁶, Jason Barnhill⁷, Liise-Anne Pirofski⁸, Johanna P Daily⁸, John M Dye⁴, Jonathan R Lai³, Andrew S Herbert⁹, Kartik Chandran¹⁰, Rohit K Jangra¹¹

Affiliations

¹ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
² Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
³ Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁴ U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
⁵ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Chemistry and Life Science, United States Military Academy at West Point, West Point, NY 10996, USA.
⁶ Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA.
⁷ Department of Chemistry and Life Science, United States Military Academy at West Point, West Point, NY 10996, USA.
⁸ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA.
⁹ U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA; The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA 98402, USA. Electronic address: [email protected].
¹⁰ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: [email protected].
¹¹ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: [email protected].

Abstract

There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.

Keywords: ACE2; COVID-19; SARS-CoV-2; VSV; antiviral drugs; convalescent plasma; neutralization assay; neutralizing antibody; serology; surrogate.

Publication types

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

MeSH terms

Angiotensin-Converting Enzyme 2
Animals
Antiviral Agents / pharmacology
Betacoronavirus / genetics
Betacoronavirus / pathogenicity*
Betacoronavirus / physiology
COVID-19
COVID-19 Drug Treatment
COVID-19 Vaccines
Cell Line
Chlorocebus aethiops
Coronavirus Infections / drug therapy
Coronavirus Infections / genetics
Coronavirus Infections / immunology
Coronavirus Infections / prevention & control
Coronavirus Infections / therapy
Coronavirus Infections / virology*
Drug Evaluation, Preclinical
Host Microbial Interactions / drug effects
Host Microbial Interactions / genetics
Host Microbial Interactions / physiology
Humans
Mutation
Neutralization Tests
Pandemics / prevention & control
Peptidyl-Dipeptidase A / genetics
Peptidyl-Dipeptidase A / physiology
Pneumonia, Viral / prevention & control
Pneumonia, Viral / therapy
Pneumonia, Viral / virology*
Receptors, Virus / genetics
Receptors, Virus / physiology
Recombination, Genetic
SARS-CoV-2
Serine Endopeptidases / physiology
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / physiology*
Vero Cells
Vesicular stomatitis Indiana virus / genetics
Vesicular stomatitis Indiana virus / physiology*
Viral Vaccines / genetics
Viral Vaccines / immunology
Virus Internalization
Virus Replication / genetics

Substances

Antiviral Agents
COVID-19 Vaccines
Receptors, Virus
Spike Glycoprotein, Coronavirus
Viral Vaccines
spike protein, SARS-CoV-2
Peptidyl-Dipeptidase A
ACE2 protein, human
Angiotensin-Converting Enzyme 2
Serine Endopeptidases
TMPRSS2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding