Cutting Edge: Serum but Not Mucosal Antibody Responses Are Associated with Pre-Existing SARS-CoV-2 Spike Cross-Reactive CD4+ T Cells following BNT162b2 Vaccination in the Elderly

  1. Lil Meyer-Arndt
  2. Tatjana Schwarz
  3. Lucie Loyal
  4. Larissa Henze
  5. Beate Kruse
  6. Manuela Dingeldey
  7. Kübrah Gürcan
  8. Zehra Uyar-Aydin
  9. Marcel A Müller
  10. Christian Drosten
  11. Friedemann Paul
  12. Leif E Sander
  13. Ilja Demuth
  14. Roland Lauster
  15. Claudia Giesecke-Thiel
  16. Julian Braun
  17. Victor M Corman
  18. Andreas Thiel

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Abstract

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine in old (69–92 y) and middle-aged (24–57 y) vaccinees compared with natural infection (COVID-19 convalescents, 21–55 y of age). Serological humoral responses to vaccination excee-ded those of convalescents, but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+ T cells as a predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.

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  1. Version published to 10.4049/jimmunol.2100990
  2. Version published to 10.1101/2021.10.05.21264545v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.10.05.21264545: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Participants and ethics: The study was approved by the ethics committee of Charité – Universitätsmedizin Berlin (EA/152/20) and was conducted in accordance with the Declaration of Helsinki.
    Consent: A written informed consent was obtained from all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: No positivity thresholds have yet been validated for saliva.

    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 ( REA671 , Miltenyi)
    suggested: None
    Surrogate virus neutralization assay (sVNT): A competition ELISA-based surrogate virus neutralization assay (sVNT; medac) mimicking the SARS-CoV-2 receptor (ACE2) binding process was used to identify neutralizing anti-SARS-CoV-2 antibodies in participant serum and saliva23,24.
    ACE2
    suggested: None
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Data processing and statistical analysis: Study data were collected and managed using REDCap electronic data capture tools hosted at Charité25,26.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Flow cytometry data were analysed using FlowJo 10 (BD)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Prism 9 (GraphPad) was used for data plotting.
    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 10.1101/2021.10.05.21264545v1 on medRxiv