Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination

  1. Tina Schmidt
  2. Verena Klemis
  3. David Schub
  4. Janine Mihm
  5. Franziska Hielscher
  6. Stefanie Marx
  7. Amina Abu-Omar
  8. Laura Ziegler
  9. Candida Guckelmus
  10. Rebecca Urschel
  11. Sophie Schneitler
  12. Sören L. Becker
  13. Barbara C. Gärtner
  14. Urban Sester
  15. Martina Sester

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Abstract

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals ( n  = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost ( n  = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens ( n  = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

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  1. Version published to 10.1038/s41591-021-01464-w
  2. ScreenIT

    SciScore for 10.1101/2021.06.13.21258859: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the ethics committee of the Ärztekammer des Saarlandes (reference 76/20), and all individuals gave written informed consent.
    Consent: The study was approved by the ethics committee of the Ärztekammer des Saarlandes (reference 76/20), and all individuals gave written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Quantification of lymphocyte populations and plasmablasts: T cells, B cells and plasmablasts were quantified from 100 µl heparinized whole blood as described before8 using monoclonal antibodies towards CD3 (clone SK7), CD19 (clone HIB19), CD27 (clone L128), CD38 (clone HB7) and IgD (clone IA6-2).
    CD3
    suggested: None
    CD19
    suggested: (Agilent Cat# TC67401, RRID:AB_579635)
    CD27
    suggested: None
    CD38
    suggested: None
    IgD
    suggested: None
    All stimulations were carried out in presence of co-stimulatory antibodies against CD28 and CD49d (1μg/ml each).
    antibodies against CD28
    suggested: (Novus Cat# NB100-93558, RRID:AB_1236789)
    CD49d
    suggested: None
    Determination of SARS-CoV-2-specific antibodies and neutralization capacity: SARS-CoV-2-specific IgG antibodies towards the receptor binding domain of SARS-CoV-2 spike protein were quantified using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (SARS-CoV-2-QuantiVac, Euroimmun, Lübeck, Germany).
    SARS-CoV-2-specific IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Analysis was carried out using GraphPad Prism 9.0 software (GraphPad, San Diego, CA, USA) using two-tailed tests.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Cytokine profiles were plotted using the VennDiagram package (version 1.6.20)20 running under R (version 4.0.2).
    VennDiagram
    suggested: (VennDiagram, RRID:SCR_002414)

    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 10.1101/2021.06.13.21258859 on medRxiv