VSV-Based Vaccines Reduce Virus Shedding and Viral Load in Hamsters Infected with SARS-CoV-2 Variants of Concern.

Kyle L O’Donnell,Wakako Furuyama,Kyle Shifflett,Tylisha Gourdine,Paige Fletcher,Chad S Clancy,Andrea Marzi

doi:10.3390/vaccines10030435

Kyle L O’Donnell, Wakako Furuyama + Show 5 more

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https://doi.org/10.3390/vaccines10030435

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Abstract

The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of concern (VOC). The existing vaccines implemented on a global scale are based on the ancestral strain, which has resulted in increased numbers of breakthrough infections as these VOC have emerged. It is imperative to show protection against VOC infection with newly developed vaccines. Previously, we evaluated two vesicular stomatitis virus (VSV)-based vaccines expressing the SARS-CoV-2 spike protein alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV) and demonstrated their fast-acting potential. Here, we prolonged the time to challenge; we vaccinated hamsters intranasally (IN) or intramuscularly 28 days prior to infection with three SARS-CoV-2 VOC—the Alpha, Beta, and Delta variants. IN vaccination with either the VSV-SARS2 or VSV-SARS2-EBOV resulted in the highest protective efficacy as demonstrated by decreased virus shedding and lung viral load of vaccinated hamsters. Histopathologic analysis of the lungs revealed the least amount of lung damage in the IN-vaccinated animals regardless of the challenge virus. This data demonstrates the ability of a VSV-based vaccine to not only protect from disease caused by SARS-CoV-2 VOC but also reduce viral shedding.

Highlights

Publisher’s Note: MDPI stays neutralEarly during the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it became apparent that greater challenges lay ahead in comparison to the outbreaks caused by SARS-CoV and MERS-CoV in 2002 and 2012, respectively
We sought to investigate the protective efficacy of our vesicular stomatitis virus (VSV)-based COVID-19 vaccines with a longer time between vaccination and challenge to expand upon the previous study showing protective efficacy within 10 days [33]
We included the vaccines VSV-SARS2EBOV, which is based on the licensed Ebola virus (EBOV) vaccine, and the VSV-SARS2 in our studies

Summary

Introduction

Publisher’s Note: MDPI stays neutralEarly during the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it became apparent that greater challenges lay ahead in comparison to the outbreaks caused by SARS-CoV and MERS-CoV in 2002 and 2012, respectively. SARS-CoV-2 can spread effectively from people that are pre-symptomatic or asymptomatic, making surveillance and epidemiology challenging [1]. As the virus continued to spread, it accumulated mutations, leading to newly emerging viral variants circumventing the growing resistance the population was acquiring through vaccination and natural infection [2–5]. One of the emerging SARS-CoV-2 variants of concern (VOC), the. Alpha variant, had acquired 23 mutations within the spike (S) protein to increase binding affinity to the ACE2 receptor and undergone a deletion of amino acids (aa) 69 and 70 that has been associated with increased viral escape in immunocompromised individuals [6]. The Beta variant harbors similar S protein mutations in addition to N501Y, E484K, and with regard to jurisdictional claims in published maps and institutional affiliations

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