Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults

  1. Mark J. Mulligan
  2. Kirsten E. Lyke
  3. Nicholas Kitchin
  4. Judith Absalon
  5. Alejandra Gurtman
  6. Stephen Lockhart
  7. Kathleen Neuzil
  8. Vanessa Raabe
  9. Ruth Bailey
  10. Kena A. Swanson
  11. Ping Li
  12. Kenneth Koury
  13. Warren Kalina
  14. David Cooper
  15. Camila Fontes-Garfias
  16. Pei-Yong Shi
  17. Özlem Türeci
  18. Kristin R. Tompkins
  19. Edward E. Walsh
  20. Robert Frenck
  21. Ann R. Falsey
  22. Philip R. Dormitzer
  23. William C. Gruber
  24. Uğur Şahin
  25. Kathrin U. Jansen

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  1. ScreenIT

    SciScore for 10.1101/2020.06.30.20142570: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: The final protocol and informed consent document were approved by institutional review boards for each of the participating investigational centers This study was conducted in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and the ethical principles of the Declaration of Helsinki.
    IRB: Both an internal review committee (IRC) and an external data monitoring committee (EDMC) reviewed all safety data.
    RandomizationProcedures: Study participants were randomly assigned to a vaccine group using an interactive web-based response technology system with each group comprising 15 participants (12 active vaccine recipients and 3 placebo recipients).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableStudy design: This study was conducted in healthy men and nonpregnant women 18 to 55 years of age to assess the safety, tolerability, and immunogenicity of ascending dose levels of various BNT162 mRNA vaccine candidates.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Bound human anti-RBD antibodies were detected with a R-Phycoerythrin-conjugated goat anti-human polyclonal secondary antibody (Jackson Labs).
    anti-RBD
    suggested: None
    anti-human polyclonal secondary antibody (Jackson Labs).
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Viral master stocks used for the neutralization assay were grown in Vero E6 cells as previously described.
    Vero E6
    suggested: RRID:CVCL_XD71)
    20 Serial dilutions of heat inactivated sera were incubated with the reporter virus for 1 hour at 37°C before inoculating Vero CCL81 cell monolayers in 96 well plates to allow accurate quantification of infected cells.
    Vero CCL81
    suggested: None
    Software and Algorithms
    SentencesResources
    Total cell counts per well were enumerated by nuclear stain (Hoechst 33342) and fluorescent virally infected foci were detected 16-24 hours after inoculation with a Cytation 7 Cell Imaging Multi-Mode Reader (Biotek) with Gen5 Image Prime version 3.09.
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    Titers were calculated in GraphPad Prism version 8.4.2 by generating a 4-parameter (4PL) logistical fit of the percent neutralization at each serial serum dilution.
    GraphPad Prism
    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: We detected the following sentences addressing limitations in the study:
    Our study had several limitations. While we used convalescent sera as a comparator, the kind of immunity (T cells versus B cells or both) and level of immunity needed to protect from COVID-19 are unknown. Further, this analysis of available data did not assess immune responses or safety beyond 2 weeks after the second dose of vaccine. Both are important to inform the public health use of this vaccine. Follow-up will continue for all participants and will include collection of serious adverse events for 6 months, and COVID-19 infection and multiple additional immunogenicity measurements through up to two years. While our population of healthy adults 55 years of age and younger is appropriate for a Phase 1/2 study, it does not accurately reflect the population at highest risk for COVID-19. Adults 65 years of age and over have already been enrolled in this study and results will be reported as they become available. Later phases of this study will prioritize enrollment of more diverse populations, including those with chronic underlying health conditions and from racial/ethnic groups adversely affected by COVID-19.19 These clinical findings for the BNT162b1 RNA-based vaccine candidate are encouraging and strongly support accelerated clinical development and at-risk manufacturing to maximize the opportunity for the rapid production of a SARS-CoV-2 vaccine to prevent COVID-19 disease.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04368728Active, not recruitingStudy to Describe the Safety, Tolerability, Immunogenicity, …

    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.

    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 10.1038/s41586-020-2639-4
  3. ScreenIT

    SciScore for 10.1101/2020.06.30.20142570: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe final protocol and informed consent document were approved by institutional review boards for each of the participating investigational centers This study was conducted in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and the ethical principles of the Declaration of Helsinki.RandomizationAvailable Results Study Design and Demographics Between 04 May 2020 and 19 June 2020, 76 subjects were screened, and 45 participants were randomized and vaccinated.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableThe study population consisted of healthy male and nonpregnant female participants with a mean age of 35.4 years (range 19 to 54 years); 51.1% were male and 48.9% were female.Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Bound human anti-RBD antibodies were detected with a R-Phycoerythrin-conjugated goat anti-human polyclonal secondary antibody (Jackson Labs).
    anti-RBD
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>anti-human polyclonal secondary antibody (Jackson Labs).</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Experimental Models: Cell Lines</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Viral master stocks used for the neutralization assay were grown in Vero E6 cells as previously described.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Vero E6</b></div>
        <div>suggested: <a href="https://scicrunch.org/resources/Any/search?q=CVCL_XD71">CVCL_XD71</a></div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">20 Serial dilutions of heat inactivated sera were incubated with the reporter virus for 1 hour at 37⁰C before inoculating Vero CCL81 cell monolayers in 96 well plates to allow accurate quantification of infected cells.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Vero CCL81</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Role of the funding source: BioNTech is the Sponsor of the study.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>BioNTech</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Data Sharing Statement: Upon request, and subject to review, Pfizer will provide the data that support the findings of this study.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Pfizer</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Total cell counts per well were enumerated by nuclear stain (Hoechst 33342) and fluorescent virally infected foci were detected 16-24 hours after inoculation with a Cytation 7 Cell Imaging Multi-Mode Reader (Biotek) with Gen5 Image Prime version 3.09.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Gen5</b></div>
        <div>suggested: (Gen5, <a href="https://scicrunch.org/resources/Any/search?q=SCR_017317">SCR_017317</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Titers were calculated in GraphPad Prism version 8.4.2 by generating a 4parameter (4PL) logistical fit of the percent neutralization at each serial serum dilution.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>GraphPad Prism</b></div>
        <div>suggested: (GraphPad Prism, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002798">SCR_002798</a>)</div>
      </div>
    </td></tr></table>

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.06.30.20142570v1 on medRxiv