Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

Steven A Kwilas,Lucia M Principe,Rebecca L Brocato,Xiankun Zeng,Jay W Hooper,Robert K Kim,Jeffrey M Smith

doi:10.1038/s41541-020-00279-z

Steven A Kwilas, Lucia M Principe + Show 5 more

Open Access

https://doi.org/10.1038/s41541-020-00279-z

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Abstract

A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

Highlights

The COVID-19 pandemic has necessitated the rapid development of candidate vaccines and treatments targeting the SARS-CoV-2
The plasmid backbone used for this vaccine, pWRG, has been used for hantavirus DNA vaccines that are currently in phase 1 and 2 clinical trials[12]
Sera were collected after 1 vaccination (Wk 3) or 2 vaccinations (Wk 5) and evaluated in a SARS-CoV-2 plaque reduction neutralization test (PRNT) and pseudovirion neutralization assay (PsVNA)

Summary

Introduction

The COVID-19 pandemic has necessitated the rapid development of candidate vaccines and treatments targeting the SARS-CoV-2. We describe the testing of a jet-injected SARS-CoV-2 DNA vaccine in both wild-type and transiently-immunosuppressed hamsters. In the first vaccine efficacy experiment, groups of 8 hamsters were vaccinated on week 0 and 3 with either 0.2 mg nCoV-S(JET), or 0.2 mg of a MERS-CoV DNA vaccine, or PBS using jet injection (Fig. 1a).

Results

Conclusion