Abstract
The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-∆G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in-vivo model for COVID-19 is implemented. We show that a single-dose vaccination results in a rapid and potent induction of SARS-CoV-2 neutralizing antibodies. Importantly, vaccination protects hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss, and alleviation of the extensive tissue damage and viral loads in lungs and nasal turbinates. Taken together, we suggest the recombinant VSV-∆G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2.
Highlights
The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization
The recombinant Vesicular stomatitis virus (VSV) platform was developed by John Rose and Michael Whitt9,10. rVSV was previously developed as a vaccine platform for several viral pathogens, including Ebola virus (EBOV), human immunodeficiency virus, and Crimean–Congo hemorrhagic fever virus[11,12]
Primary recovery of the VSV-ΔGspike was performed in BHK-21 cells infected with Modified Vaccinia Ankara T7 (MVA-T7), followed by cotransfection with the rVSV-ΔG-spike, and the VSV accessory plasmids encoding for VSV-N, P, L, and G proteins under control of a T7 promoter (Fig. 1c)
Summary
The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. We show the development of a replication competent recombinant VSV-ΔG-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. SARS-CoV-2 is a single-stranded positive sense RNA virus decorated with the spike (S) surface glycoprotein. The S protein binds with high affinity to the angiotensin-converting enzyme 2 (ACE2) receptor This binding induces membrane fusion and entry of the SARSCoV-2 into host cells, serving as a target for neutralizing antibodies[5,6]. It has been recently shown that the SARS-CoV-2 has a newly formed furin cleavage site at the S1/S2 boundary This novel feature dramatically affects viral entry into Vero E6 and BHK-21 cells[6]. RVSV harbors several advantages: (1) The virus can be propagated and reach high titers, (2) it elicits strong cellular and humoral immunity in vivo, (3) elimination of the VSV-G protein, the major virulence factor of the VSV, attenuates the virus and reduces its reactogenicity, (4) VSV is sensitive to IFN-α/β, and an intact innate immune response likely restricts its replication[13], and (5) most of the general population is seronegative for VSV14
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