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Authors: Yahalom-Ronen*, Tamir* et al.,  

Journal/ Pre-Print:BioRxV 

Tags: Structural biology, Vaccines, Virology 

Research Highlights

  1. rVSV-∆G-spike vaccine involved replacing the glycoprotein (viral binding and cell entry) of Vesicular Stomatitis Virus with the Spike protein from SARS-CoV-2 

  1. rVSV-∆G-spike was neutralised by COVID-19 convalescent serum so can serve as a surrogate for SARS-CoV-2 

  1. rVSV-∆G-spike was safe and eliminated the lung viral load in a challenge model using golden Syrian hamster 

Summary

The authors applied the established Vesicular Stomatitis Virus (VSV) vaccine platform to SARS-CoV-2 by replacing the VSV glycoprotein with the SARS-CoV-spike protein (rVSV-∆G-spike). After 13 passages in VeroE6 cells the construct was replicating successfully (3x107 pfu/ml) alongside increase of S gene expression and elimination of the VSV-G gene. Three mutations emerged during this process which are hypothesised to aid the rVSV-∆G-spike virus stability and ability to propagate in Vero cellsrVSV-∆G-spike was neutralised by SARS-CoV-2 convalescent serum and showed efficacy in vivo using a golden Syrian hamster model. Different doses (104-108 pfu) of the rVSV-∆G-spike vaccine were administered intramuscularly or subcutaneously. Hamsters were challenged 4 weeks later with 5x106 pfu SARS-CoV-2 intranasally. Single-dose vaccination was safe, reduced viral titres to undetectable levels, induced SARS-CoV-2 neutralising antibodies, abrogated weight loss and reduced lung pathology. 

Impact for SARS-CoV-2/COVID19 research efforts  

Develop a vaccine for SARS-CoV-2/COVID19 

Study Type  

  • In vitro study – Vero E6 cell line 

  • In vivo study – golden Syrian hamster in vivo model for COVID-19 

Strengths and limitations of the paper 

Novelty: Development of a novel vaccine that is safe and provides protection against COVID-19 in golden Syrian hamsters  

Standing in the field:Details the generation and testing of a novel vaccine approach for SARS-CoV-2. Minimal detailed phenotyping in this initial study leaving several open questions 

Appropriate statistics: Statistics not shown for several graphs and no quantification of imaging. Not entirely clear what test is done based on figure legend e.g. Fig8M  

Viral model used:SARS-CoV-2-infected golden Syrian hamsters 

Translatability:Vaccine development so potentially translatable, but several unanswered questions are outstanding  

Main limitations:  

  • Would be good to assess the viral load in the nose or stool given concerns over viral spread 

  • What is the effect of the vaccine on T cell responses? Which cells are in the lung? Would be possible given that they have performed lung pathology on day 5 

  • i.m. and s.c. route of administration employed but don’t directly compare or discuss why both used 

  • Would be good to assess the duration of protection and any additive effect of a vaccine boost (challenge 4 weeks after vaccination) 

  • Would be good to pursue the effect of the spike protein mutations in more detail. Can mutations be intentionally introduced to improve efficacy?   

  • VSV as a vaccine vector, although approved for Ebola, shows notable adverse events. The safety profile of VSV based vaccines might be a limiting factor in their development.