Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine

  1. Yihao Liu
  2. Qin Zeng
  3. Caiguanxi Deng
  4. Mengyuan Li
  5. Liubing Li
  6. Dayue Liu
  7. Ming Liu
  8. Xinyuan Ruan
  9. Jie Mei
  10. Ruohui Mo
  11. Qian Zhou
  12. Min Liu
  13. Sui Peng
  14. Ji Wang
  15. Hui Zhang
  16. Haipeng Xiao

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a nonrandomized trial among the healthcare workers (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 arbitrary units (AU)/mL to 8.8 AU/mL 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/mL by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4 + and CD8 + T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to two doses were not truly “non-responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.

Article activity feed

  1. Version published to 10.1038/s41421-022-00373-7
  2. Version published to 10.1101/2021.09.12.21263373v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.09.12.21263373: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: All studies were approved by the Institutional Review Board of FAH-SYSU and written consent was obtained from all participants.
    Consent: All studies were approved by the Institutional Review Board of FAH-SYSU and written consent was obtained from all participants.
    Field Sample Permit: Cell isolation: Blood samples were collected into the heparinized tubes and processed right after sample collection
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were incubated with IFN-γ detection antibody (1μg/ml, MabTech, #3420-6-250), followed by Avidin-HRP (1μg/ml, Vector, #A-2004-5) and visualized using the ACE substrate.
    #A-2004-5
    suggested: None
    , Tocris, #4536/10) and IL-2 (20 ng/ml, PeproTech, #200-02-10) for 3 days to secrete a detectable amount of antibody28, 29.
    IL-2
    suggested: None
    antibody28
    suggested: None
    anti-CD69-Super Bright 436, anti-CD134 (OX40)-BV605 and anti-CD137-(4-1BB)-PE antibodies for antigen-specific T cell analysis.
    anti-CD134
    suggested: None
    anti-CD137-
    suggested: None
    4-1BB)-PE
    suggested: None
    As for phenotype analysis of SARS-CoV-2-specific T cells, cells were further labeled with anti-CCR7-APC/cy7, anti-CD45RA-BV650, anti-CXCR5-BV711 and anti-PD-1-PE/cy7 antibodies.
    anti-CCR7-APC/cy7
    suggested: None
    anti-CD45RA-BV650
    suggested: None
    anti-CXCR5-BV711
    suggested: None
    anti-PD-1-PE/cy7
    suggested: None
    Cells were washed with PBS and then stained with the following antibody cocktail: anti-CD3-Pacific Blue™, anti-CD19-PE-CY7, anti-CD27-AF700, anti-IgD-FITC, anti-CD38-BV650, anti-IgM-BV605, anti-IgG-AF647, anti-IgA-PE all from BioLegend at 1:100 dilution.
    anti-CD3-Pacific
    suggested: None
    anti-CD19-PE-CY7
    suggested: None
    anti-CD27-AF700
    suggested: None
    anti-IgD-FITC
    suggested: (Miltenyi Biotec Cat# 130-099-633, RRID:AB_2659770)
    anti-CD38-BV650
    suggested: None
    anti-IgM-BV605
    suggested: None
    anti-IgG-AF647
    suggested: None
    anti-IgA-PE
    suggested: (Miltenyi Biotec Cat# 130-093-128, RRID:AB_1036158)
    Plates were washed 3 times by PBST, processed to 100 μl/well goat HRP conjugated anti-human IgG antibody (2040-05, SouthernBiotech) at 1:3000 dilution in PBST for staining in 30 minutes at room temperature.
    anti-human IgG
    suggested: (SouthernBiotech Cat# 2040-05, RRID:AB_2795644)
    Software and Algorithms
    SentencesResources
    FlowJo
    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.

    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 10.1101/2021.09.12.21263373v1 on medRxiv