Preliminary Immunogenicity of a Pan-COVID-19 T Cell Vaccine in HLA-A*02:01 Mice

  1. Brandon Carter
  2. Jinjin Chen
  3. Clarety Kaseke
  4. Alexander Dimitrakakis
  5. Gaurav D. Gaiha
  6. Qiaobing Xu
  7. David K. Gifford

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Abstract

New strains of SARS-CoV-2 have emerged, including B.1.351 and P.1, that demonstrate increased transmissibility and the potential of rendering current SARS-CoV-2 vaccines less effective. A concern is that existing SARS-CoV-2 spike subunit vaccines produce neutralizing antibodies to three dimensional spike epitopes that are subject to change during viral drift. Here we provide an initial report on the hypothesis that adaptive T cell based immunity may provide a path for a pan-COVID-19 vaccine that is resilient to viral drift. T cell based adaptive immunity can be based on short peptide sequences selected from the viral proteome that are less subject to drift, and can utilize multiple such epitopes to provide redundancy in the event of drift. We find that SARS-CoV-2 peptides contained in a mRNA-LNP T cell vaccine for SARS-CoV-2 are immunogenic in mice transgenic for the human HLA-A*02:01 gene. We plan to test the efficacy of this vaccine with SARS-CoV-2 B.1.351 challenge trials with HLA-A*02:01 mice.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.02.442052: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    2.4 Vaccine administration: A total of nine HLA-A*02:01 human transgenic mice (Jackson Laboratories Number 003475) were used.
    HLA-A*02:01
    suggested: None
    Software and Algorithms
    SentencesResources
    Detection of interferon gamma positive spots was performed with a Cellular Technologies Limited CTL S6 FluoroSpot reader, and analyzed with ImmunoSpot 5.1.36 software.
    ImmunoSpot
    suggested: (ImmunoSpot Software for Analyzing ELISPOT Assays, RRID:SCR_011082)

    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:
    The lack of immunogenicity for these five peptides could be possibly a result of (1) incomplete processing of vaccine peptides in mouse HLA transgenics, as noted for other nucleic acid vaccines (Street et al., 2002), (2) the very high immunogenicity of YLYALVYFL may have competed against the immunogenicity of other peptides, (3) limitations in the T cell repertoire in the inbred HLA-A*02:01 mouse strains, and (4) the vaccine construct we created is too long for the vaccine to be optimally effective. However, we note that peptides both at the beginning and end of the construct were found to be immunogenic. The observed immunogenicity of SARS-CoV-2 peptides YLYALVYFL and TVYSHLLLV (MHC class I), as well as PLYAFASEAARVVRSI (MHC class II) suggests that the vaccine may provide protection against high titers of SARS-CoV-2 viral infection.

    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.

  2. Version published to 10.1101/2021.05.02.442052 on bioRxiv