Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

  1. Rüdiger Groß
  2. Michelle Zanoni
  3. Alina Seidel
  4. Carina Conzelmann
  5. Andrea Gilg
  6. Daniela Krnavek
  7. Sümeyye Erdemci-Evin
  8. Benjamin Mayer
  9. Markus Hoffmann
  10. Stefan Pöhlmann
  11. Weimin Liu
  12. Beatrice H. Hahn
  13. Alexandra Beil
  14. Joris Kroschel
  15. Bernd Jahrsdörfer
  16. Hubert Schrezenmeier
  17. Frank Kirchhoff
  18. Jan Münch
  19. Janis A. Müller

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Abstract

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  1. Version published to 10.1016/j.ebiom.2021.103761
  2. Version published to 10.1101/2021.05.30.21257971v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.30.21257971: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Collection of serum and PBMC samples: Blood samples from individuals were obtained after recruitment of participants and written informed consent as approved by the ethics committee of Ulm university (99/21).
    IRB: Collection of serum and PBMC samples: Blood samples from individuals were obtained after recruitment of participants and written informed consent as approved by the ethics committee of Ulm university (99/21).
    Sex as a biological variableCell culture: Vero E6 (African green monkey, female, kidney; CRL-1586, ATCC, RRID:CVCL_0574) cells were grown in Dulbecco’s modified Eagle’s medium (DMEM, Gibco) which was supplemented with 2.5% heat-inactivated fetal calf serum (FCS), 100 units/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine, 1 mM sodium pyruvate, and 1x non-essential amino acids.
    RandomizationLongitudinal antibody measurements were analyzed by means of a mixed linear regression model including a random intercept in order to account for the repeated measures structure of the underlying data.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Determination of antibody titers: IgG and IgA levels in serum were determined by anti-SARS-CoV-2 assay (Euroimmun), an ELISA which detects antibodies against the SARS-CoV-2 S1 spike domain.
    anti-SARS-CoV-2 assay ( Euroimmun)
    suggested: None
    Cell culture medium containing anti-VSV-G antibody (I1-hybridoma cells; ATCC no. CRL-2700) was then added to block residual VSV-G-containing particles.
    anti-VSV-G
    suggested: (LSBio (LifeSpan Cat# LS-C51092-40, RRID:AB_1277788)
    Without washing, cells were incubated with surface antibody cocktail (prepared in 1:1 of FACS buffer and brilliant staining buffer) for 30 minutes at room temperature with BV510-anti-human CD14 (clone M5E2), BV510-anti-human CD19 (clone HIB19),
    BV510-anti-human CD14
    suggested: None
    BV510-anti-human CD19
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell culture: Vero E6 (African green monkey, female, kidney; CRL-1586, ATCC, RRID:CVCL_0574) cells were grown in Dulbecco’s modified Eagle’s medium (DMEM, Gibco) which was supplemented with 2.5% heat-inactivated fetal calf serum (FCS), 100 units/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine, 1 mM sodium pyruvate, and 1x non-essential amino acids.
    Vero E6
    detected: (IZSLER Cat# BS CL 87, RRID:CVCL_0574)
    HEK293T (human, female, kidney; ACC-635, DSMZ, RRID: CVCL_0063) cells were grown in DMEM with supplementation of 10% FCS, 100 units/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine.
    HEK293T
    detected: (CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)
    One day after transfection of HEK293T cells to express the viral glycoprotein, they were inoculated with VSV*ΔG-FLuc and incubated for 1-2 h at 37°C.
    HEK293T
    suggested: None
    Recombinant DNA
    SentencesResources
    A replication-deficient VSV vector in which the genetic information for VSV-G was replaced by genes encoding two reporter proteins, enhanced green fluorescent protein and firefly luciferase (FLuc), VSV*ΔG-FLuc 24 (kindly provided by Gert Zimmer, Institute of Virology and Immunology, Mittelhäusern, Switzerland) (
    VSV-G
    suggested: RRID:Addgene_138479)
    Software and Algorithms
    SentencesResources
    Results are given as serum dilution resulting in 50% virus neutralization (NT50) on cells, calculated by nonlinear regression ([Inhibitor] vs. normalized response -- Variable slope) in GraphPad Prism Version 9.1.1
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Up to 100,000 live CD3+ T cells were acquired on a LSRFortessa flow cytometer (BD Biosciences), equipped with FACS Diva software.
    BD Biosciences
    suggested: (BD Biosciences, RRID:SCR_013311)
    Analysis of the acquired data was performed using FlowJo software (version 10.7.1).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    All analyses were done by GraphPad Prism version 9.1.1 for Windows, GraphPad Software, San Diego, California USA, www.graphpad.com, R (version 4.0.1) and SAS (version 9.4).
    GraphPad
    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: 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.

  4. Version published to 10.1101/2021.05.30.21257971v1 on medRxiv