A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

Delphine C Malherbe,Julie M Williams,Matthew A Hyde,Chad Mire,Alexander Bukreyev,Noor Shaik,Adam J Ronk,Sivakumar Periasamy,Matthias J Schnell,Drishya Kurup,Christoph Wirblich,Natalia Kuzmina,Pei-Yong Shi

doi:10.1038/s41541-021-00352-1

Abstract

The development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal models of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

Highlights

The development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority
CoV, SARS-CoV-2, and porcine coronavirus utilized vesicular stomatitis virus (VSV) and rabies virus as vector backbones to express the spike protein as immunogen[5,6,7,8,9]
We previously developed a MERS vaccine candidate in which the S1 domain of the MERS spike protein was fused to the C-terminal part of the rabies virus glycoprotein to allow incorporation and display on the surface of virions[9]

Summary

Introduction

The development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. Comparative pathology scores for lungs from SARS-CoV-2-infected and mock-infected hamsters (two animals in each group) were determined 2 days (D2) and 4 days (D4) post challenge (d–h).

Results

Conclusion