A SARS-CoV-2 peptide vaccine which elicits T-cell responses in mice but does not protect against infection or disease

  1. Victoria K. Baxter
  2. Elizabeth J. Anderson
  3. Sharon A. Taft-Benz
  4. Kelly Olsen
  5. Maria Sambade
  6. Kaylee M. Gentry
  7. Wolfgang Beck
  8. Jason Garness
  9. Allison Woods
  10. Misha Fini
  11. Brandon Carpenter
  12. Christof C. Smith
  13. Mark T. Heise
  14. Benjamin Vincent
  15. Alex Rubinsteyn

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Abstract

We vaccinated BALB/c mice with peptides derived from the SARS-CoV-2 proteome selected in silico to elicit T-cell responses and/or B-cell responses against linear epitopes. These peptides were administered in combination with either of two adjuvants, poly(I:C) and the STING agonist BI-1387466. Antibody responses against predicted linear epitopes were not observed but both adjuvants consistently elicited T-cell responses to the same peptides, which were primarily from the set chosen for predicted T-cell immunogenicity. The magnitude of T-cell responses was significantly higher with BI-1387466 compared with poly(I:C). Neither adjuvant group, however, provided any protection against infection with the murine adapted virus SARS-CoV-2-MA10 or from disease following infection. In light of more recent evidence for protection from severe disease mediated by CD8+ T-cells, we suspect that the epitopes selected for vaccination were not presented by infected murine cells.

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  1. Version published to 10.1101/2022.02.22.481499v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2022.02.22.481499: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Mouse vaccination for immunogenicity study: All mouse work was performed according to IACUC guidelines under UNC IACUC protocol ID 20-121.0.
    Euthanasia Agents: On 5 days post infection (DPI), mice were euthanized by an overdose of isoflurane anesthesia, and lungs were collected.
    Sex as a biological variableEqual numbers of male and female mice were used per group, vaccinated subcutaneously with poly(I:C) (Sigma-Aldrich cat.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum was plated in duplicate wells with serial dilutions, and anti-FLAG antibody was plated in the experimental control wells.
    anti-FLAG
    suggested: None
    Rabbit anti-mouse IgG HRP (Abcam ab97046) was utilized as a secondary antibody.
    anti-mouse IgG
    suggested: (Abcam Cat# ab97046, RRID:AB_10680920)
    Goat anti-mouse IgG HRP (Thermo Fisher Scientific) was added to washed plates as a secondary antibody.
    Goat anti-mouse IgG HRP
    suggested: None
    anti-mouse IgG HRP
    suggested: None
    Anti-interferon gamma detection antibody was added according to the manufacturer’s protocol, followed by enzyme conjugate Streptavidin-HRP and final substrate solution (BD Biosciences; cat. #557630).
    Anti-interferon
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse vaccination for viral challenge: Using the same IACUC protocol described above, female BALB/c mice were used, 5 per group.
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    Anti-interferon gamma detection antibody was added according to the manufacturer’s protocol, followed by enzyme conjugate Streptavidin-HRP and final substrate solution (BD Biosciences; cat. #557630).
    BD Biosciences
    suggested: (BD Biosciences, RRID:SCR_013311)

    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: We detected the following sentences addressing limitations in the study:
    Due to the contradictions and ambiguity of previous animal studies and the limitations of this one, further research is required to disentangle these distinct interpretations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.
    • No funding statement was detected.
    • 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 10.1101/2022.02.22.481499v1 on bioRxiv