Kinetics and Persistence of the Cellular and Humoral Immune Responses to BNT162b2 mRNA Vaccine in SARS-CoV-2-Naive and -Experienced Subjects: Impact of Booster Dose and Breakthrough Infections

  1. Salomé Desmecht
  2. Aleksandr Tashkeev
  3. Majdouline El Moussaoui
  4. Nicole Marechal
  5. Hélène Perée
  6. Yumie Tokunaga
  7. Celine Fombellida-Lopez
  8. Barbara Polese
  9. Céline Legrand
  10. Marie Wéry
  11. Myriam Mni
  12. Nicolas Fouillien
  13. Françoise Toussaint
  14. Laurent Gillet
  15. Fabrice Bureau
  16. Laurence Lutteri
  17. Marie-Pierre Hayette
  18. Michel Moutschen
  19. Christelle Meuris
  20. Pieter Vermeersch
  21. Daniel Desmecht
  22. Souad Rahmouni
  23. Gilles Darcis

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Abstract

Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the cellular and humoral immune response in healthcare workers up to 12 months after the initial vaccination, with one additional boosting dose between 6 and 12 months.

Methods

This prospective study enrolled 208 healthcare workers (HCWs) from the Liège University Hospital (CHU) of Liège in Belgium. Participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 months later. Fifty participants were SARS-CoV-2 experienced and 158 were naïve before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3), 6 months (T4) and 12 months (T5) after the second dose. Between T4 and T5, participants also got the third boosting vaccine dose. A total of 1145 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies, using the DiaSorin LIAISON SARS-CoV-2 Trimeric S IgG assay, and for anti-Nucleocapsid antibodies, using Elecsys anti-SARS-CoV-2 assay​​. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization assay. Cell-mediated immune response was evaluated at T4 and T5 on 80 and 55 participants, respectively, by measuring the secretion of IFN-γ on peripheral blood lymphocytes using the QuantiFERON Human IFN-γ SARS-CoV-2, from Qiagen. We analyzed separately the naïve and experienced participants.

Findings

We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced HCWs compared to naïve HCWs at all time points analyzed except the one after boosting dose. Cellular immune response was also higher in experienced HCWs six months following vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative association between age and persistence of humoral response. The booster dose induced an increase in humoral and cellular immune responses, particularly in naive individuals. Breakthrough infections resulted in higher cellular and humoral responses after the booster dose.

Conclusions

Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. The benefit of the booster dose was greater in naive individuals. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses.

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  1. Version published to 10.3389/fimmu.2022.863554
  2. ScreenIT

    SciScore for 10.1101/2022.01.17.22269278: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: They all acknowledged that they had understood the study protocol and signed the informed consent.
    IRB: The protocol was approved by the ethics committee (full name: comité d’éthique hospitalo-facultaire universitaire de Liège) of Liège University Hospital (approval number 2021-54).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Assessment of total anti-spike IgGs: The DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin, Stillwater, USA), a chemiluminescent immunoassay using magnetic particles coated with recombinant trimeric SARS-CoV-2 spike protein, was used for quantitative determination of IgG antibodies in human serum samples.
    anti-spike IgGs
    suggested: None
    Separating individuals with neutralizing versus non-neutralizing antibodies by anti-S IgG: Logistic regression of neutralizing status at the last time point (T4 at 6 months post-vaccine, 1st dose) on the log of anti-Spike IgG was used to determine the threshold immunoglobulin value that provides the best separation of the classes.
    anti-S IgG
    suggested: None
    anti-Spike IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus isolation, expansion, titration and SNT analysis were all performed using nonadherent sub-confluent Vero E6 cells (ATCC® CRL-1586) grown in DMEM supplemented with 2% FBS and penicillin-streptomycin.
    Vero E6
    suggested: None
    After incubation, 100 μl of a Vero cells suspension were added so that 20,000 cells were deposited in each well (19).
    Vero
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04796896RecruitingA Study to Evaluate Safety and Effectiveness of mRNA-1273 CO…

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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

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  3. Version published to 10.1101/2022.01.17.22269278v1 on medRxiv