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

  1. Kyle L. O’Donnell
  2. Chad S. Clancy
  3. Amanda J. Griffin
  4. Kyle Shifflett
  5. Tylisha Gourdine
  6. Tina Thomas
  7. Carrie M. Long
  8. Wakako Furuyama
  9. Andrea Marzi

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

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.

Article activity feed

  1. Version published to 10.3389/fimmu.2021.788235
  2. ScreenIT

    SciScore for 10.1101/2021.09.03.458735: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: All procedures followed standard operating procedures (SOPs) approved by the RML Institutional Biosafety Committee (
    Sex as a biological variableAnimal study: Two hundred and fifty Syrian golden hamsters (5-8 weeks of age; male and female) were used in this study.
    RandomizationThe hamsters were randomly selected into groups as shown in table S2.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After horse-radish peroxidase (HRP)-labeled secondary antibody staining using either anti-mouse IgG (1:10,000) or anti-rabbit IgG (1:5000) (Jackson ImmunoResearch), the blots were imaged using the SuperSignal West Pico chemiluminescent substrate (Thermo Fisher Scientific) and an iBright™ CL1500 Imaging System (Thermo Fisher Scientific)
    anti-rabbit IgG
    suggested: None
    After three washes with PBST, the bound antibodies were labeled using 50 μl of 1:2,500 peroxidase anti-hamster IgG (H+L) (SeraCare Life Sciences) diluted in 1% skim milk in PBST.
    anti-hamster IgG
    suggested: None
    The secondary antibody was the Vector Laboratories ImPress VR anti-mouse IgG polymer (cat# MP-7422).
    anti-mouse IgG
    suggested: (Vector Laboratories Cat# MP-7422, RRID:AB_2336527)
    Experimental Models: Cell Lines
    SentencesResources
    All viruses were grown and titered on Vero E6 cells, and sequence confirmed.
    Vero E6
    suggested: RRID:CVCL_XD71)
    The replication competent recombinant VSV was recovered in BHK-T7 cells as described previously (Emanuel et al., 2018).
    BHK-T7
    suggested: None
    VSV-SARS2-EBOV was propagated in Huh7 cells.
    Huh7
    suggested: CLS Cat# 300156/p7178_HuH7, RRID:CVCL_0336)
    Recombinant DNA
    SentencesResources
    Full-length SARS-CoV-2 S was cloned into the pATX-VSV-EBOV plasmid upstream of the EBOV-Kikwit GP resulting in VSV-SARS2-EBOV (Fig.
    pATX-VSV-EBOV
    suggested: None
    The cytoplasmic tail deletion was introduced by PCR and was cloned into the pATX-VSV plasmid resulting in VSV-SARS2.
    pATX-VSV
    suggested: None
    Software and Algorithms
    SentencesResources
    Sample acquisition was performed on a FACSSymphony-A5 (BD), and data analyzed in FlowJo V10.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analyses: All statistical analysis was performed in Prism 8 (GraphPad).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.09.03.458735v1 on bioRxiv