Optimization of Single-Dose VSV-Based COVID-19 Vaccination in Hamsters.

Kyle L O’Donnell,Tina Thomas,Kyle Shifflett,Carrie M Long,Chad S Clancy,Wakako Furuyama,Amanda J Griffin,Andrea Marzi,Tylisha Gourdine

doi:10.3389/fimmu.2021.788235

Abstract

The ongoing COVID-19 pandemic has resulted in global effects on human health, economic stability, and social norms. The emergence of viral variants raises concerns about the efficacy of existing vaccines and highlights the continued need for the development of efficient, fast-acting, and cost-effective vaccines. Here, we demonstrate the immunogenicity and protective efficacy of two vesicular stomatitis virus (VSV)-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV). Intranasally vaccinated hamsters showed an early CD8+ T cell response in the lungs and a greater antigen-specific IgG response, while intramuscularly vaccinated hamsters had an early CD4+ T cell and NK cell response. Intranasal vaccination resulted in protection within 10 days with hamsters not showing clinical signs of pneumonia when challenged with three different SARS-CoV-2 variants. This data demonstrates that VSV-based vaccines are viable single-dose, fast-acting vaccine candidates that are protective from COVID-19.

Highlights

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as a novel, highly infectious, respiratory CoV and is the causative agent of Coronavirus disease 2019 (COVID-19), first described in the city of Wuhan in Hubei province in China [1]
We generated a monovalent vesicular stomatitis virus (VSV) construct by replacing the Ebola virus (EBOV) GP with the SARS-CoV-2 S which contains a cytoplasmic tail deletion previously described [28, 45]
We performed viral growth kinetics and found that VSV-SARS2EBOV replicated with similar kinetics and had comparable endpoint titers as the parental VSV-EBOV (Figure S1C)

Summary

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as a novel, highly infectious, respiratory CoV and is the causative agent of Coronavirus disease 2019 (COVID-19), first described in the city of Wuhan in Hubei province in China [1]. The World Health Organization declared the SARS-CoV-2 pandemic a Public Health Emergency of International Concern on January 30th 2020 [2]. The COVID-19 pandemic mandated the development of a VSV-SARS-CoV-2 Vaccine Protects Hamsters vaccine to be a global priority [7,8,9,10,11]. B.1.1.7 acquired 23 mutations including N501Y within the S shown to increase binding affinity to the ACE2 receptor [12, 13]. B.1.351 harbors similar mutations such as the N501Y, in addition to K417N and E484K which may reduce the efficacy of existing countermeasures [14,15,16]

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