A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition

Dieterle, M. E.; Haslwanter, D.; Bortz, R. H.; Wirchnianski, A. S.; Lasso, G.; Vergnolle, O.; Abbasi, S. A.; Fels, J. M.; Laudermilch, E.; Florez, C.; Mengotto, A.; Kimmel, D.; Malonis, R. J.; Georgiev, G.; Quiroz, J.; Barnhill, J.; Pirofski, L.-A.; Daily, J. P.; Dye, J. M.; Lai, J. R.; Herbert, A. S.; Chandran, K.; Jangra, R. K.

doi:10.1101/2020.05.20.105247

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bioRxiv · 10.1101/2020.05.20.105247

A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition

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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, and define correlates of immune protection, and to down-select candidate antivirals. Here, we describe a highly infectious recombinant vesicular stomatitis virus bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein that closely resembles the authentic agent in its entry-related properties. We show that the neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S and that neutralization of the rVSV 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 vaccines and therapeutics and for mechanistic studies of viral entry and its inhibition.

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Dieterle, M. E., Haslwanter, D., Bortz, R. H., Wirchnianski, A. S., Lasso, G., Vergnolle, O., Abbasi, S. A., Fels, J. M., Laudermilch, E., Florez, C., Mengotto, A., Kimmel, D., Malonis, R. J., Georgiev, G., Quiroz, J., Barnhill, J., Pirofski, L.-A., Daily, J. P., Dye, J. M., Lai, J. R., Herbert, A. S., Chandran, K., Jangra, R. K.. 2020-05-20. A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition. https://doi.org/10.1101/2020.05.20.105247

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