Single-dose SARS-CoV-2 vaccinations with either BNT162b2 or AZD1222 induce disparate Th1 responses and IgA production

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Abstract

Background

While vaccination programs against the severe acute respiratory syndrome virus 2 (SARS-CoV-2) are globally ongoing, disparate strategies for the deployment of spike antigen show varying effectiveness.

Methods

In order to explore this phenomenon, we sought to compare the early immune responses against AZD1222 and BNT162b2. SARS-CoV-2 seronegative participants received a single dose of either vaccine and were analyzed for immune cell, effector T cell, and antibody dynamics.

Results

AZD1222 induced transient leukopenia and major changes among innate and adaptive subpopulations. Both vaccines induced spike protein-specific effector T cells which were dominated by type 1 helper T cell responses following AZD1222 vaccination. A significant reduction of anti-inflammatory T cells upon re-stimulation was also restricted to AZD1222 vaccinees. While IgM and IgG were the dominant isotypes elicited by AZD1222, BNT162b2 led to a significant production of IgG and IgA.

Conclusions

Our results suggest that the strategy for spike protein delivery impacts on how and to what extent immune priming against the main SARS-CoV-2 antigen proceeds.

Article activity feed

  1. SciScore for 10.1101/2021.09.17.21263726: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the ethics committee of the Rostock University Medical Center under the file number A 2020-0086.
    Consent: Written informed consent was provided by all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    In order to reduce unspecific antibody-conjugate binding, 10 µL FCS, 5 µL True-Stain Monocyte Blocker™ and 5 µL anti-Fc receptor TruStain FcX™ (Biolegend, San Diego/CA, United States) were added and incubated for 15 min on ice.
    anti-Fc receptor TruStain FcX™
    suggested: (BioLegend Cat# 422302, RRID:AB_2818986)
    The following amounts of antibody:fluorophore-combinations were used: 0.25 µg CD127:APC/R700 (clone HIL-7R-M21), 1 µg CD147:BV421 (TRA-1-85), 0.5 µg CD45RO:BV480 (UCHL1, BD Biosciences, Franklin Lakes/NJ, United States), 1 µg CD11b:PerCP/Cy5.5 (ICRF44), 0.8 µg CD11c:BV785 (3.9), 0.56 µg CD14:BV510 (
    UCHL1
    suggested: (BioLegend Cat# 304233, RRID:AB_11219394)
    Surface antigens were stained by incubating the cells with following antibody:fluorophore-combinations: 1.25 µg CD3:FITC (clone UCHT1), 0.02 µg CD4:BV750 (SK3), 0.06 µg CD8:BV570 (RPA-T8), 0.5 µg Fas-L:PE (NOK1), 1 µg CD25:APC (BC96, Biolegend), 1.25 µL CD127:APC/R700 (HIL-7R-M21) and 0.25 µg CD137:BV480 (4B4-1, BD Biosciences) for 15 min at room temperature.
    antibody:fluorophore-combinations
    suggested: None
    NOK1
    suggested: None
    BC96
    suggested: None
    HIL-7R-M21
    suggested: (BD Biosciences Cat# 566101, RRID:AB_2869742)
    Software and Algorithms
    SentencesResources
    Analysis of flow cytometry data was done using FlowJo software version 10.7 (FlowJo, Ashland/OR, United States).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    4.6 Statistical Analysis: Data analyses were performed using R (version 3.5.1) and InStat version 3.10 (GraphPad, San Diego/CA, United States).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Data visualization was performed with SigmaPlot version 13.0 (Systat Software GmbH, Erkrath, Germany).
    SigmaPlot
    suggested: (SigmaPlot, RRID:SCR_003210)

    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:
    This study has a few limitations, among them the small samples sizes. Nonetheless, our results depict for both vaccines significantly disparate effects on the peripheral immune layout and on the regulation of T cell effector molecules. Another limitation is the lack of assaying neutralizing SARS-CoV-2 specific antibodies. However, previous studies have already demonstrated that total spike-binding Ig titers strongly correlate with the amounts of neutralizing antibodies and are therefore a suitable measure for humoral protection from SARS-CoV-2 infection5,40–42. In summary, we consider the description of disparate vaccine effects on the immediate immune response the strength of our study and we believe that our results will be of use for further optimization of vaccination strategies.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 7. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.