Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2

  1. Rahul Ukey
  2. Natalie Bruiners
  3. Hridesh Mishra
  4. Pankaj K. Mishra
  5. Deborah McCloskey
  6. Alberta Onyuka
  7. Fei Chen
  8. Abraham Pinter
  9. Daniela Weiskopf
  10. Alessandro Sette
  11. Jason Roy
  12. Sunanda Gaur
  13. Maria Laura Gennaro

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Abstract

Background

Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines.

Main body

We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class 5 months earlier on average. After controlling for the time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups.

Conclusions

A dichotomy exists between the humoral and cellular responses elicited by the two vaccine classes. Testing only for humoral responses to compare the durability of SARS-CoV-2 vaccine-induced responses, as typically performed for public health and research purposes, is insufficient.

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  1. Version published to 10.1186/s12916-022-02252-0
  2. ScreenIT

    SciScore for 10.1101/2021.09.17.21263528: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: All study activities were approved by the Rutgers Institutional Review Board (Pro2020000655).
    IACUC: Biosafety protocols: All work involving blood products from SARS-CoV-2-infected subjects were performed in a biosafety level 2+ (BSL-2+) laboratory utilizing protocols approved by the Rutgers Institutional Biosafety Committee.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    PBMCs were stained with fixable viability stain 780 (BD Biosciences, Franklin Lakes, USA), incubated for 10 minutes with human Fc receptor blocking reagent (BD Biosciences, Franklin Lakes, NJ, USA), and then stained with the two fluorescent RBD tetramers, antibodies to CD19-BV700 (HIB19,
    HIB19
    suggested: None
    Bio Legend, San Diego, CA, USA) and CD20-PE-CF594 (2H7, BD Biosciences, San Jose, CA, USA) to detect RBD-specific B cells, and APC-Cy7-labelled antibodies against CD3 (UCHT1), CD4 (OKT4), CD14 (C1D3), and CD16 (CD16) (all from Thermo Fisher Scientific, Waltham, MA, USA) to eliminate non-B cells.
    CD20-PE-CF594
    suggested: None
    CD3
    suggested: None
    UCHT1
    suggested: None
    CD4
    suggested: (BioLegend Cat# 391503, RRID:AB_2721611)
    CD14
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD16
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: Vero E6 were obtained from the American Type Culture Collection (ATCC), Manassas,
    Vero E6
    suggested: RRID:CVCL_XD71)
    USA; HeLa cells stably expressing ACE2 (HeLa-ACE2) were obtained from Dennis Burton at the Scripps Research Institute 2.
    HeLa
    suggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)
    SARS-CoV-2 neutralization assay: HeLa-Ace2 cells were seeded in 96-well black optical-bottom plates at a density of 1 × 104 cells/well in FluoroBrite DMEM (Thermo Fisher Scientific, Waltham, USA) containing 4% FBS (Seradigm)
    HeLa-Ace2
    suggested: None
    Software and Algorithms
    SentencesResources
    All flow cytometry data were analyzed with FlowJo v12 software (FlowJo LLC, Ashland, OR, USA).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    , StataCorp LLC, College Station, USA) and GraphPad Prism version 8.4 (Graph Pad Software Inc.,
    StataCorp
    suggested: (Stata, RRID:SCR_012763)
    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: 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 10.1101/2021.09.17.21263528v1 on medRxiv