Immunogenicity of the third and fourth BNT162b2 mRNA COVID-19 boosters and factors associated with immune response in patients with SLE and rheumatoid arthritis

  1. Theerada Assawasaksakul
  2. Seelwan Sathitratanacheewin
  3. Preeyaporn Vichaiwattana
  4. Nasamon Wanlapakorn
  5. Yong Poovorawan
  6. Yingyos Avihingsanon
  7. Nawaporn Assawasaksakul
  8. Wonngarm Kittanamongkolchai

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Abstract

To evaluate the safety and immunogenicity of third and fourth BNT162b2 boosters in patients with SLE and rheumatoid arthritis (RA).

Methods

Patients with SLE and RA aged 18–65 years who completed a series of inactivated, adenoviral vector, or heterogenous adenoviral vector/mRNA vaccines for at least 28 days were enrolled. Immunogenicity assessment was done before and day 15 after each booster vaccination. The third BNT162b2 booster was administered on day 1. Patients with suboptimal humoral response to the third booster dose (antireceptor-binding domain (RBD) IgG on day 15 <2360 BAU/mL) were given a fourth BNT162b2 booster on day 22.

Results

Seventy-one patients with SLE and 29 patients with RA were enrolled. The third booster raised anti-RBD IgG by 15-fold, and patients with positive neutralising activity against the Omicron variant increased from 0% to 42%. Patients with positive cellular immune response also increased from 55% to 94%. High immunosuppressive load and initial inactivated vaccine were associated with lower anti-RBD IgG titre. Fifty-four patients had suboptimal humoral responses to the third booster and 28 received a fourth booster dose. Although anti-RBD IgG increased further by sevenfold, no significant change in neutralising activity against the Omicron variant was observed. There were two severe SLE flares that occurred shortly after the fourth booster dose.

Conclusions

The third BNT162b2 booster significantly improved humoral and cellular immunogenicity in patients with SLE and RA. The benefit of a short-interval fourth booster in patients with suboptimal humoral response was unclear.

Trial registration number

TCTR20211220004.

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  1. Version published to 10.1136/lupus-2022-000726
  2. ScreenIT

    SciScore for 10.1101/2022.03.15.22272350: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This trial was reviewed and approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (1425/2021) and registered in the Thai Clinical Trial Registry (TCTR20211220004).
    Consent: Participants meeting eligibility criteria were invited to participate in the study and provided written informed consent.
    Sex as a biological variablenot detected.
    RandomizationThe cellular immune responses were measured by human IFNγ-ELISpot assay (ELISpot) in a random subset of patients.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We chose the anti-RBD IgG (Abbott Diagnostics) cut-off value of 2,360 BAU/mL (16,503 AU/mL) as it corresponded to vaccine efficacy of 90% for wild-type8.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis was performed using JMP software V.13.2.1 (SAS Institute, Cary, North Carolina, USA) and dot-plot graphs were created using GraphPad Prism V.4.03 (
    JMP
    suggested: (JMP, RRID:SCR_014242)
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    (GraphPad Software, La Jolla, CA, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    It should be noted that there were several limitations to this study. The findings are observational and based on a small sample size, so they should be interpreted with caution. The results may not be generalizable to other autoimmune rheumatic conditions, other immunosuppressive regimens such as B-cell depletion therapy, or initial mRNA vaccine series. The immunosuppressive load calculation was adapted from the prior study which was arbitrarily determined. In conclusion, this study demonstrated that the third BNT162b2 booster was well tolerated and significantly improved humoral and cellular immunogenicity in SLE and RA patients. The intensity of immunosuppressive therapy and the type of initial vaccine appear to affect the humoral immune response to the third booster. In poor humoral responders, a fourth BNT162b2 booster administered at a short interval may not provide additional protection against the omicron variant. Our finding that severe flares were observed in SLE patients after the fourth booster is also cause for caution and additional research on the appropriateness of a fourth booster and the timing of such booster in our population.

    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2022.03.15.22272350v1 on medRxiv