The vaccinia‐based Sementis Copenhagen Vector coronavirus disease 2019 vaccine induces broad and durable cellular and humoral immune responses

  1. Preethi Eldi
  2. Tamara H Cooper
  3. Natalie A Prow
  4. Liang Liu
  5. Gary K Heinemann
  6. Voueleng J Zhang
  7. Abigail D Trinidad
  8. Ruth Marian Guzman‐Genuino
  9. Peter Wulff
  10. Leanne M Hobbs
  11. Kerrilyn R Diener
  12. John D Hayball

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Abstract

The ongoing coronavirus disease 2019 (COVID‐19) pandemic perpetuated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus‐based, replication‐defective Sementis Copenhagen Vector (SCV) was used to develop a first‐generation COVID‐19 vaccine encoding the spike glycoprotein (SCV‐S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust type 1 T helper‐biased, spike‐specific antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated that neutralizing antibody activity was maintained up to 9 months after vaccination in both young and middle‐aged mice, with durable immune memory evident even in the presence of pre‐existing vector immunity. Therefore, SCV‐S vaccination has a positive immunogenicity profile, with potential to expand protection generated by current vaccines in a heterologous boost format and presents a solid basis for second‐generation SCV‐based COVID‐19 vaccine candidates incorporating additional SARS‐CoV‐2 immunogens.

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  1. Version published to 10.1111/imcb.12539
  2. ScreenIT

    SciScore for 10.1101/2021.09.06.459206: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All experiments were conducted under protocols approved by the University of South Australia Animal Ethics Committee in accordance with the Australian code for the care and use of animals for scientific purposes, 8th edition (2013).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were harvested at 24 hrs, stained with live-dead marker (LIVE/DEAD fixable e660 stain, Thermo Fisher Scientific; 1/3000 dilution) and anti-SARS-CoV-2 RBD antibody (Cat # 40592-T62, Sino Biological; 1:100 dilution), followed by staining with PE-conjugated donkey anti-rabbit IgG (Cat # 406421, Biolegend), data was acquired using a FACSARIA Fusion™ (BD Biosciences), and analysis performed using FlowJo V10 software.
    anti-SARS-CoV-2 RBD
    suggested: None
    anti-rabbit IgG
    suggested: (BioLegend Cat# 406421, RRID:AB_2563484)
    Plates were then washed and incubated with biotinylated anti-mouse IFN-γ antibody (clone R4-6A2; Mabtech; 1 μg/mL) followed by streptavidin-alkaline phosphatase (Mabtech; 1:1,000 dilution).
    anti-mouse IFN-γ
    suggested: None
    Memory T cell populations were identified by staining for surface markers with the following anti-mouse antibodies (BD Biosciences): CD3 APC-CY7 (clone 17A2, 1:400); CD4 BV510 (clone RM4-5, 1:400); CD8a PE (clone 53-6.7,
    anti-mouse
    suggested: None
    CD4
    suggested: (Miltenyi Biotec Cat# 130-109-536, RRID:AB_2657974)
    Binding serum antibodies were detected using HRP-conjugated anti-mouse IgG (Cat #A9044, Sigma Aldrich, 1:10,000)
    anti-mouse IgG
    suggested: (Sigma-Aldrich Cat# A9044, RRID:AB_258431)
    Plates were subsequently washed, incubated with biotinylated anti-IgG detection antibody (Mabtech, 1 μg/mL), followed by streptavidin-alkaline phosphatase (Mabtech, 1:1,000 dilution).
    anti-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    MC57G cells (ATCC CRL-2295) for chromium release assays were maintained in Eagle’s Minimum Essential medium supplemented with 10% FBS, 2 mM L-glutamine, and penicillin-streptomycin.
    MC57G
    suggested: ATCC Cat# CRL-2295, RRID:CVCL_4985)
    Spike protein expression by flow cytometry: To confirm processing of the spike protein and surface translocation, 143B cells were infected with SCV-S or SCV control (empty) vector with an MOI of 1 or left uninfected.
    143B
    suggested: ECACC Cat# 91112502, RRID:CVCL_2270)
    ACE2-HEK293 cells were plated at a density of 10,000 cells/well in a clear bottomed white opaque 96-well plate and incubated at 37°C.
    ACE2-HEK293
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Animal experiments: Specific-pathogen-free inbred C57BL/6J and outbred Swiss mouse heritage Arc:Arc(S) mice were bred in house or purchased from the Animal Resources Centre (Canning Vale, WA, Australia).
    C57BL/6J
    suggested: RRID:IMSR_JAX:000664)
    Software and Algorithms
    SentencesResources
    Following washing, the membrane was incubated with anti-rabbit IgG antibody conjugated to horseradish peroxidase (Cat # A9044, Sigma Aldrich; 1:10,000 dilution) for 1 hr at RT and proteins visualized using Clarity ECL western blotting substrate (BioRad) and imaged using ChemiDoc XRS (BioRad).
    Sigma Aldrich
    suggested: (Sigma-Aldrich, RRID:SCR_008988)
    Cells were harvested at 24 hrs, stained with live-dead marker (LIVE/DEAD fixable e660 stain, Thermo Fisher Scientific; 1/3000 dilution) and anti-SARS-CoV-2 RBD antibody (Cat # 40592-T62, Sino Biological; 1:100 dilution), followed by staining with PE-conjugated donkey anti-rabbit IgG (Cat # 406421, Biolegend), data was acquired using a FACSARIA Fusion™ (BD Biosciences), and analysis performed using FlowJo V10 software.
    Thermo Fisher Scientific
    suggested: (Thermo Fisher Scientific, RRID:SCR_008452)
    Cells were washed, resuspended in 150 µL FACS buffer, and results acquired on FACSARIA Fusion™ with analysis by FlowJo V10 software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Memory T cell populations were identified by staining for surface markers with the following anti-mouse antibodies (BD Biosciences): CD3 APC-CY7 (clone 17A2, 1:400); CD4 BV510 (clone RM4-5, 1:400); CD8a PE (clone 53-6.7,
    BD Biosciences)
    suggested: None
    IC80 titers were determined using a log (inhibitor) vs. normalized-response (variable slope) nonlinear regression model in Prism v9 (GraphPad)
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistics: GraphPad Prism version 9.0 (GraphPad software) was used for data analysis and statistics.
    Statistics: GraphPad Prism
    suggested: None

    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 10.1101/2021.09.06.459206v1 on bioRxiv