A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge
structural biology vaccines virology
Authors: Yahalom-Ronen*, Tamir* et al.,
Tags: Structural biology, Vaccines, Virology
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
rVSV-∆G-spike was neutralised by COVID-19 convalescent serum so can serve as a surrogate for SARS-CoV-2
rVSV-∆G-spike was safe and eliminated the lung viral load in a challenge model using golden Syrian hamster
The authors applied the established Vesicular Stomatitis Virus (VSV) vaccine platform to SARS-CoV-2 by replacing the VSV glycoprotein with the SARS-CoV-2 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 cells. rVSV-∆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
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
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.