Comprehensive humoral and cellular immune responses to SARS-CoV-2 variants in diverse Chinese populations: A benefit perspective of national vaccination

  1. Jiwei Li
  2. Jing Wu
  3. Qiuyue Long
  4. Yanan Wu
  5. Xiaoyi Hu
  6. Yukun He
  7. Mingzheng Jiang
  8. Jia Li
  9. Lili Zhao
  10. Shuoqi Yang
  11. Xiaoyong chen
  12. Minghui Wang
  13. Jianshi Zheng
  14. Fangfang Wu
  15. Ruiliang Wu
  16. Lihong Ren
  17. Liang Bu
  18. Houzhao Wang
  19. Ke Li
  20. Lijuan Fu
  21. Guojun Zhang
  22. Yali Zheng
  23. Zhancheng Gao

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Abstract

The emerging SARS-CoV-2 variants have made great challenges to current vaccine and pandemic control strategies. B.1.1.529 (Omicron), which was classified as a variant of concern (VOC) by the World Health Organization on November 26th, 2021, has quickly become the dominant circulating variant and causing waves of infections. It is urgent to understand the current immune status of the general population given that pre-existing immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases suffered a breakthrough infection after vaccination, and 49 vaccinated participants without infection history), we showed that the cross-neutralizing activity against VOCs such as Omicron can be detected in 53 (62.4%) cases, although less potent than against the Wuhan-1 strain (WT), with a 3.9-fold reduction in geometric mean neutralizing titer (GMT) (130.7, 95% CI 88.4-193.3 vs 506, 355.8-719.7, respectively). Subgroup analysis revealed significantly enhanced neutralizing activity against WT and VOCs in Delta convalescent sera. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy donors (p = 0.006), with a GMT of 289.5, 180.9-463.3 and 42.6, 31.3-59, respectively. However, the protective effect against VOCs was weaker in young convalescents (aged < 18y), with a detectable rate of 50% and a GMT of 46.4 against Omicron, similar to vaccinees. The pan-sarbecovirus neutralizing activities were not observed in vaccinated SARS-CoV-1 survivors. A booster dose significantly increased the breadth and magnitude of neutralization against WT and VOCs to different degrees than full vaccination. In addition, we showed that COVID-19 inactivated vaccines can elicit Omicron-specific T cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively. The neutralizing antibody titers declined while T-cell responses remain robust over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.13.22270896: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    PBMC were surface stained with fluorescently labeled antibodies to CD3 (FITC), CD19 (PE/Cyanine7), CD4 (PerCP/Cyanine5.5), CD8a (APC), CD56 (BV421), and CD16 (PE) in the dark at 4°C for 30 min.
    CD3
    suggested: None
    CD19
    suggested: None
    CD4
    suggested: (BioLegend Cat# 391503, RRID:AB_2721611)
    CD8a
    suggested: (Meridian Life Science Cat# MAL16-154, RRID:AB_1070035)
    CD56
    suggested: None
    BV421
    suggested: None
    CD16
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell Lines: HEK293T cells were purchased from Procell and cultured in DMEM supplemented with 10% fetal bovine serum (FBS).
    HEK293T
    suggested: None
    Since SARS-CoV-2 uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry and the transmembrane serine protease 2 (TMPRSS2) for S protein priming, we co-transfected plasmids encoding ACE2 (pLV-ACE2-3xFLAG-IRES-puro, HedgehogBio Science and Technology Ltd.) and TMPRSS2 (pLV-TMPRSS2-GFP, Sino Biological) into 293T cells to generate a stable cell line.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Neutralization assays were performed on 293T-ACE2-TMPRSS2 cells.
    293T-ACE2-TMPRSS2
    suggested: None
    Recombinant DNA
    SentencesResources
    Since SARS-CoV-2 uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry and the transmembrane serine protease 2 (TMPRSS2) for S protein priming, we co-transfected plasmids encoding ACE2 (pLV-ACE2-3xFLAG-IRES-puro, HedgehogBio Science and Technology Ltd.) and TMPRSS2 (pLV-TMPRSS2-GFP, Sino Biological) into 293T cells to generate a stable cell line.
    pLV-ACE2-3xFLAG-IRES-puro
    suggested: None
    pLV-TMPRSS2-GFP
    suggested: None
    Software and Algorithms
    SentencesResources
    15 Statistical analysis: Data and statistical analyses were performed using GraphPad Prism 8.0.2 and SPSS 26.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Flow cytometry data were analyzed using FlowJo 10.4.0.
    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.

  2. Version published to 10.1101/2022.02.13.22270896 on medRxiv
  3. Version published to 10.34133/2022/9873831