mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

  1. Ellie N. Ivanova
  2. Jasmine Shwetar
  3. Joseph C. Devlin
  4. Terkild B. Buus
  5. Sophie Gray-Gaillard
  6. Akiko Koide
  7. Amber Cornelius
  8. Marie I. Samanovic
  9. Alberto Herrera
  10. Eleni P. Mimitou
  11. Chenzhen Zhang
  12. Trishala Karmacharya
  13. Ludovic Desvignes
  14. Niels Ødum
  15. Peter Smibert
  16. Robert J. Ulrich
  17. Mark J. Mulligan
  18. Shohei Koide
  19. Kelly V. Ruggles
  20. Ramin S. Herati
  21. Sergei B. Koralov

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Abstract

SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell dataset of peripheral blood of patients with acute COVID-19 and of healthy volunteers before and after receiving the SARS-CoV-2 mRNA vaccine and booster. We compared host immune responses to the virus and vaccine using transcriptional profiling, coupled with B/T cell receptor repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. These findings were validated in an independent dataset. Analysis of B and T cell repertoires revealed that, while the majority of clonal lymphocytes in COVID-19 patients were effector cells, clonal expansion was more evident among circulating memory cells in vaccine recipients. Furthermore, while clonal αβ T cell responses were observed in both COVID-19 patients and vaccine recipients, dramatic expansion of clonal γδT cells was found only in infected individuals. Our dataset enables comparative analyses of immune responses to infection versus vaccination, including clonal B and T cell responses. Integrating our data with publicly available datasets allowed us to validate our findings in larger cohorts. To our knowledge, this is the first dataset to include comprehensive profiling of longitudinal samples from healthy volunteers pre/post SARS-CoV-2 vaccine and booster.

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  1. Version published to 10.1101/2021.04.20.21255677v3 on medRxiv
  2. Version published to 10.1101/2021.04.20.21255677v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.04.20.21255677: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Peripheral blood was collected in accordance with a NYU Institutional Review Board protocols (IRB 18-02035, 18-02037 and 20-00463).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We detected antigen-specific antibodies in heat-inactivated serum or plasma using anti-human IgG-Alexa 488 (Jackson Immunoresearch; catalog number 109-545-098, 1:800 in PBS 0.1 % Tween 20 and with 1 % BSA), anti-human IgA-PE (Jackson Immunoresearch; catalog number 109-115-011, 1:100) and anti-human IgM-DyLight405 (Jackson Immunoresearch; catalog number 709-475-073, 1:200).
    antigen-specific
    suggested: None
    anti-human IgG-Alexa
    suggested: None
    anti-human IgA-PE
    suggested: (SouthernBiotech Cat# 2050-09, RRID:AB_2795707)
    anti-human IgM-DyLight405
    suggested: None
    Software and Algorithms
    SentencesResources
    Single cell RNA-seq data processing: The Cellranger software suite (https://support.10xgenomics.com/single-cell-gene-expression/software/pipelines/latest/what-is-cell-ranger) from 10X was used to demultiplex cellular barcodes, align reads to the human genome (GRCh38 ensemble, http://useast.ensembl.org/Homo_sapiens/Info/Index) and perform UMI counting.
    https://support.10xgenomics.com/single-cell-gene-expression/software/pipelines/latest/what-is-cell-ranger
    suggested: (Cell Ranger , RRID:SCR_017344)
    We measured the samples on a Yeti ZE5 Cell Analyzer (Bio-Rad) and analyzed the data using FlowJo (BD, version 10.7.1).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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

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  4. Version published to 10.1101/2021.04.20.21255677v1 on medRxiv