Characterizing cellular and molecular variabilities of peripheral immune cells in healthy inactivated SARS-CoV-2 vaccine recipients by single-cell RNA sequencing

  1. Renyang Tong
  2. Jianmei Zhong
  3. Ronghong Li
  4. Yifan Chen
  5. Liuhua Hu
  6. Zheng Li
  7. Jianfeng Shi
  8. Guanqiao Lin
  9. Yuyan Lyu
  10. Li Hu
  11. Xiao Guo
  12. Qi Liu
  13. Tian Shuang
  14. Chenjie Zhang
  15. Ancai Yuan
  16. Minchao Zhang
  17. Wei Lin
  18. Jun Pu

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Abstract

We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios.

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    SciScore for 10.1101/2021.05.06.21256781: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Participants and ethics: All human samples used in this study were processed under Institutional Review Board approved protocols at Shanghai Jiao Tong University.
    Consent: All study participants were recruited after providing informed consent and with approval by the Ethics Committee of Ren Ji Hospital (KY2021-046), School of Medicine, Shanghai Jiao Tong University, and the study was conducted according to the criteria set by the Declaration of Helsinki31 (2013).
    Sex as a biological variableSix healthy non-frail individuals who had not received any vaccine in the past one year were recruited in the Pu Dong Cohort, China, including 4 males and 2 females, aged 30-40 years old.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody and Serum cytokine detection: The levels of anti-SARS-CoV-2 (2019-nCoV) Spike RBD IgG in serum were tested using Sino Biological® SARS-CoV-2 (2019-nCoV) Spike RBD Antibody Titer Assay Kit (Catalog Number: KIT002) following the manufacturer’s instructions.
    anti-SARS-CoV-2
    suggested: None
    Samples were incubated with anti-IL-4 capture antibody coated magnetic beads and biotinylated detection antibody to form the immuno-complex.
    anti-IL-4
    suggested: None
    Software and Algorithms
    SentencesResources
    Single-Cell Data Processing: The matrices of unique molecular identifier (UMI) were generated for each sample by the Cell Ranger (10× Genomics, Version 4.0.0) Pipeline coupled with human reference version GRCh38 (10× Genomics, Version 3.0.0.) using STAR (version 2.5.1b).
    STAR
    suggested: (STAR, RRID:SCR_004463)
    Additionally, we applied DoubletFinder package (version 2.0.2) to identify potential doublets. 3.
    DoubletFinder
    suggested: (DoubletFinder, RRID:SCR_018771)
    For each cell, we normalized the gene expression profiles with SCT-transform in Seurat package.
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    GO and KEGG pathway enrichment analyses on these DEGs identify the biological keywords, that allowed us to summarize the keywords of classical immune responsive signal.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    The regulons expression profile cluster plots were visualized using the ComplexHeatmap package of R.
    ComplexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)

    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: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. Due to the currently high cost of single-cell sequencing and inaccessibility of other vaccine type at the moment, the coverage and the size of sampling of this study are relatively limited, which limits the power of this study. Due to the urgent need of COVID-19 related research, the follow-up time couldn’t be long enough, either. Despite of these limitations, we were able to observe the protective immunity induced by BBIBP-CorV at the single-cell level and identified a set of genes that not only featured the immune-responsive variation of the peripheral immune cells but also exhibited many interpretable signaling pathways. The signature expression described in here might facilitate to design a new assay to assess the immune protection and adverse effects after the vaccination or infection recovery.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04871932RecruitingCOVID-2019 Vaccine Immune Response Base on Single Cell Multi…

    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.

  2. Version published to 10.1101/2021.05.06.21256781v1 on medRxiv