Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

  1. Hassen Kared
  2. Asia-Sophia Wolf
  3. Amin Alirezaylavasani
  4. Anthony Ravussin
  5. Guri Solum
  6. Trung The Tran
  7. Fridtjof Lund-Johansen
  8. John Torgils Vaage
  9. Lise Sofie Nissen-Meyer
  10. Unni C. Nygaard
  11. Olav Hungnes
  12. Anna H. Robertson
  13. Lisbeth Meyer Næss
  14. Lill Trogstad
  15. Per Magnus
  16. Ludvig A. Munthe
  17. Siri Mjaaland

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Abstract

The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (T FH ) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG + B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.

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  1. Version published to 10.1038/s41467-022-31888-y
  2. ScreenIT

    SciScore for 10.1101/2022.01.13.22269213: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Donors signed informed consent forms.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    KLRG1 Monoclonal Antibody (13F12F2), eBioscience,
    KLRG1
    suggested: None
    Peptide stimulation was performed in the presence of costimulatory antibodies against CD28 and CD49d (BD Biosciences) and Brefeldin-A (10 μg/mL, Millipore Sigma).
    antibodies against CD28
    suggested: (Novus Cat# NB100-93558, RRID:AB_1236789)
    CD49d
    suggested: None
    Antibody staining panel setup: Purified CD19 (Biolegend), TCRVα7.2, CD160 and KLRG1 (R&D Systems) antibodies lacking carrier proteins (100 μg/antibody) were conjugated to DN3 MAXPAR chelating polymers loaded with heavy metal isotopes following the recommended labelling procedure (Fluidigm).
    CD19
    suggested: None
    TCRVα7.2
    suggested: None
    CD160
    suggested: None
    174Yb anti-PD anti-1/CD279
    174Yb
    suggested: (Fluidigm Cat# 3143013, RRID:AB_2661810)
    anti-PD
    suggested: (Abcam Cat# ab120611, RRID:AB_11157298)
    Cells were washed, and each well was then stained with 100 μL of a unique double metal–labelled (Y89, Cd-106, Cd-110, Cd-112, Cd-116 and Cd-196) anti-CD45 antibody mix to further barcode the cells of individual donor.
    anti-CD45
    suggested: None
    All Antibodies were purchased from BD biosciences except towards Blimp-1 and IRF4 (Thermofischer) and IgM, CD71 and HLA-DR (Biolegend).
    IRF4
    suggested: None
    IgM , CD71
    suggested: None
    HLA-DR
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    One Million cells per donor samples, healthy donor PBMCs and VeriCells were seeded in 96-well plate.
    VeriCells
    suggested: None
    Software and Algorithms
    SentencesResources
    All participants had received both doses of SARS-CoV-2 vaccines (either BNT162 or mRNA-1273) according to the Norwegian National Vaccination Program.
    Norwegian National Vaccination Program
    suggested: None
    Data analysis was performed using CYTOGRAPHER® (ImmunoScape cloud based analytical software), custom R-scripts, GraphPad Prism (GraphPad Software) and FlowJo v10 software (BD Life Sciences).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    The Delta breakthrough samples were in addition stimulated with mutated Spike peptides (PepTivator
    PepTivator
    suggested: None
    The rest of the following mAbs were directly purchased from Fluidigm: y89 anti-CD45, 106Cd anti-CD45, 110Cd anti-CD45
    Fluidigm
    suggested: (Fluidigm CyTOF, RRID:SCR_021055)
    Each sample was manually de-barcoded followed by gating on live CXCR5+CD4+ T cells for TFH analysis (CD45+ DNA+ cisplatin− CD3+ cells) after gating out residual antigen-presenting cells (HLA-DR+CD3- such as monocytes (CD14) and B cells (CD19) using FlowJo (Tree Star) software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    A correlation matrix was calculated comparing phenotypic and serological marker variables in a pairwise fashion, using the corr.test function from the psych CRAN package; the corrplot package was subsequently used to graphically display the correlation matrix.
    CRAN
    suggested: (CRAN, RRID:SCR_003005)

    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 10.1101/2022.01.13.22269213v1 on medRxiv