Cross-reactive CD4 + T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

  1. Lucie Loyal
  2. Julian Braun
  3. Larissa Henze
  4. Beate Kruse
  5. Manuela Dingeldey
  6. Ulf Reimer
  7. Florian Kern
  8. Tatjana Schwarz
  9. Maike Mangold
  10. Clara Unger
  11. Friederike Dörfler
  12. Shirin Kadler
  13. Jennifer Rosowski
  14. Kübrah Gürcan
  15. Zehra Uyar-Aydin
  16. Marco Frentsch
  17. Florian Kurth
  18. Karsten Schnatbaum
  19. Maren Eckey
  20. Stefan Hippenstiel
  21. Andreas Hocke
  22. Marcel A. Müller
  23. Birgit Sawitzki
  24. Stefan Miltenyi
  25. Friedemann Paul
  26. Marcus A. Mall
  27. Holger Wenschuh
  28. Sebastian Voigt
  29. Christian Drosten
  30. Roland Lauster
  31. Nils Lachman
  32. Leif-Erik Sander
  33. Victor M. Corman
  34. Jobst Röhmel
  35. Lil Meyer-Arndt
  36. Andreas Thiel
  37. Claudia Giesecke-Thiel

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Abstract

There is mounting evidence that immunological memory after infection with seasonal human coronaviruses (hCoVs) contributes to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loyal et al . identified a universal immunodominant coronavirus peptide found within the fusion peptide domain of coronavirus spike protein. This peptide is recognized by CD4 + T cells in 20% of unexposed individuals, more than 50% of SARS-CoV-2 convalescents, and 97% of subjects treated with the Pfizer–BioNTech COVID-19 vaccine. Although ubiquitous, these coronavirus-reactive T cells decreased with age, which may explain in part the increased susceptibility of elderly people to COVID-19. —STS

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  1. Version published to 10.1126/science.abh1823
  2. ScreenIT

    SciScore for 10.1101/2021.04.01.21252379: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study subjects: This study was approved by the Institutional Review board of the Charité (EA/152/20) and written informed consent was obtained from all participants included (38).
    Consent: Study subjects: This study was approved by the Institutional Review board of the Charité (EA/152/20) and written informed consent was obtained from all participants included (38).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Surface staining was performed for 15 min in the presence of 1 mg/ml Beriglobin (CSL Behring) with the following fluorochrome-conjugated antibodies titrated to their optimal concentrations: CD3-FITC (REA613, Miltenyi), CD4-VioGreen (REA623, Miltenyi), CD8-VioBlue (REA734, Miltenyi), CD38-APC (REA671, Miltenyi), HLA-DR-PerCpVio700 (REA805, Miltenyi).
    CD8-VioBlue
    suggested: (Miltenyi Biotec Cat# 130-094-152, RRID:AB_10828909)
    CD38-APC
    suggested: None
    anti-human-IgG secondary antibody (Jackson Immunoresearch) was diluted 1:5000 (Jackson Immunoresearch) and added to the serum samples for 1 h at 30°C, then HRP substrate was added (TMB, Kem-En-Tec).
    anti-human-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1 spike glycoprotein peptide pool 1 or 2 (all from JPT) at concentrations of 1 µg/ml per peptide respectively.
    HCoV-NL63
    suggested: RRID:CVCL_RW88)
    Vero E6 cells (1.6 ×105 cells/well) were seeded in 24-well plates overnight.
    Vero E6
    suggested: None
    Plated Vero cells were incubated with 200µl serum-virus solution.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    PBMCs were isolated by gradient density centrifugation according to the manufacturer’s instructions (Leucosep tubes, Greiner; Biocoll, Bio&SELL)
    Bio&SELL
    suggested: None
    Data analysis and statistics: Study data were collected and managed using REDCap electronic data capture tools hosted at Charité (43, 44).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Flow cytometry data were analyzed with FlowJo 10.6 (FlowJo LLC) and statistical analysis conducted with GraphPad Prism 9.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    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.

    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 10.1101/2021.04.01.21252379v1 on medRxiv