Optimization of Single-Dose VSV-Based COVID-19 Vaccination in Hamsters

Abstract

The ongoing COVID-19 pandemic has resulted in global effects on human health, economic stability, and social norms. The emergence of viral variants raises concerns about the efficacy of existing vaccines and highlights the continued need for the development of efficient, fast-acting, and cost-effective vaccines. Here, we demonstrate the immunogenicity and protective efficacy of two vesicular stomatitis virus (VSV)-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV). Intranasally vaccinated hamsters showed an early CD8+ T cell response in the lungs and a greater antigen-specific IgG response, while intramuscularly vaccinated hamsters had an early CD4+ T cell and NK cell response. Intranasal vaccination resulted in protection within 10 days with hamsters not showing clinical signs of pneumonia when challenged with three different SARS-CoV-2 variants. This data demonstrates that VSV-based vaccines are viable single-dose, fast-acting vaccine candidates that are protective from COVID-19.

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

“…We went on to show significant reductions in viral RNA in oral swabs of all vaccinated hamsters, regardless of vaccination route when challenged with the Alpha or Beta variants. IN vaccination regardless of the vaccine resulted in significant reduction of viral RNA in the oral swabs of Delta-challenged hamsters, consistent with previous findings in which IN vaccination was the most efficacious in a 10-day time to chal-lenge study [33]. Taken together, these data suggest that a VSV-based vaccine successfully prevents severe lower respiratory disease associated with SARS-CoV-2 VOC infection and, importantly, may significantly reduce viral spread in the acute phase of infection.…”

“…While the cross-reactive cellular response is maintained in the majority of individuals, the functionality of the cross-reactive antibody response declines dramatically [45][46][47][48]. We have previously demonstrated vaccine efficacy similar to the results presented here, inhibiting infection of the lungs and no effect on oral viral shedding [33]. This study highlights both of those attributes when the single vaccination was administered a longer time before challenge.…”

“…We sought to investigate the protective efficacy of our 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-SARS2-EBOV, which is based on the licensed EBOV vaccine, and the VSV-SARS2 in our studies.…”

“…VSVs expressing the SARS-CoV-2 S protein either alone (VSV-SARS2) or in combination with the EBOV GP (VSV-SARS2-EBOV) were used in this study. The generation of both vaccines, growth kinetics, and antigen expression have been previously described [ 33 ]. Briefly, for VSV-SARS2-EBOV, the SARS-CoV-2 S gene was PCR-amplified and cloned into the pATX-VSV-EBOV upstream of the EBOV GP.…”

“…Several routes of vaccination, including intramuscular (IM) and intranasal (IN) routes, have demonstrated VSV-based vaccine efficacy against various viral pathogens, including Ebola virus (EBOV), Marburg virus, Lassa virus, Andes virus, Zika virus, and highly pathogenic avian influenza virus in animal models [ 23 , 28 , 29 , 30 , 31 , 32 ]. We have previously demonstrated the fast-acting potential of VSV-based SARS-CoV-2 vaccines in hamsters [ 33 ] and nonhuman primates (NHPs) [ 34 ]. In this study we sought to determine whether a 28-day vaccination to challenge schedule would confirm vaccine efficacy against multiple VOC.…”