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

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.

Fighting Fire with Fire: Immunogenicity of Viral Vectored Vaccines against COVID-19

“…A broad spectrum of alternative viral vectors has also undergone extensive preclinical evaluation, including in vesicular stomatitis virus (VSV)-based vaccines. In hamsters, IM immunization of 2 × 10 7 PFU of ConVac, a VSV-based vaccine expressing the S1 subunit of S, induced NAb titers that were 100-fold higher than those of sham control animals, and protected animals from SARS-CoV-2 replication in the lung [47]. Of note, similar levels of SARS-CoV-2-specific antibodies were observed in ConVac-vaccinated hamsters and a recovered COVID-19 patient [47].…”

“…In hamsters, IM immunization of 2 × 10 7 PFU of ConVac, a VSV-based vaccine expressing the S1 subunit of S, induced NAb titers that were 100-fold higher than those of sham control animals, and protected animals from SARS-CoV-2 replication in the lung [47]. Of note, similar levels of SARS-CoV-2-specific antibodies were observed in ConVac-vaccinated hamsters and a recovered COVID-19 patient [47]. Another study of a recombinant VSV-G-spike SARS-CoV-2 vaccine assessed how dosage (ranging from 10 4 to 10 8 pfu) affected antibody production [48].…”

“…In addition to the VVVs described above, VSV-, measles virus-, and yellow fever virusbased vaccines have also demonstrated the ability to induce T H 1-oriented responses in various preclinical studies [47][48][49]51,52,55]. Last but not least, the aforementioned OV-spike vaccine was also shown to induce SARS-CoV-2-specific T cell responses in tumor-free and tumor-bearing mice [59].…”

Pseudotyped Vesicular Stomatitis Virus-Severe Acute Respiratory Syndrome-Coronavirus-2 Spike for the Study of Variants, Vaccines, and Therapeutics Against Coronavirus Disease 2019

“…Overall, all findings emphasize the relevance of CT of these glycoproteins in the production of virus-like particles and virion, including pseudotyped viruses. Pseudotyped VSV virions have been used to assess cellular tropism, glycoprotein function, receptor recognition, and neutralization antibody assay in viruses from risk groups 3 and 4 (Table 1), including Crimean-Congo hemorrhagic fever virus, Ebola virus, Marburg virus, Lassa Takada et al, 1997;Geisbert and Feldmann, 2011;Lennemann et al, 2017;Saito et al, 2020 Marburg virus GP Vaccine and drug testing GFP Geisbert and Feldmann, 2011;Zhang et al, 2017;Saito et al, 2020 Lassa virus GP Entry and receptor mechanism, and neutralization assays GFP Kunz et al, 2005;Hastie et al, 2017 Nipah virus G/F Fusion mechanism and neutralization assays GFP and SEAP Kaku et al, 2009Kaku et al, , 2012Tamin et al, 2009;Contreras et Condor Capcha et al, 2020;Gasbarri et al, 2020;Collier et al, 2021;Malherbe et al, 2021;Tolah et al, 2021;Verma et al, 2021 GP, glycoprotein; GFP, green fluorescent protein; SEAP, secreted alkaline phosphatase; F, fusion; G, attachment.…”

“…Furthermore, ppVSV G-SARS-CoV-2 S are being utilized in the development of a vaccine against SARS-CoV-2. Thus, various VSV-SARS-CoV-2 vaccines have been shown in animal models to be effective in both generating neutralizing antibodies at high titers and protecting against the SARS-CoV-2 challenge (Case et al, 2020a;Yahalom-Ronen et al, 2020;Lu et al, 2021;Malherbe et al, 2021). Although the evidence provided by these vector vaccines is encouraging, it is still early in the research process, and additional study is needed before moving forward with human trials.…”