An Association Study of HLA with the Kinetics of SARS-CoV-2 Spike Specific IgG Antibody Responses to BNT162b2 mRNA Vaccine

  1. Seik-Soon Khor
  2. Yosuke Omae
  3. Junko S. Takeuchi
  4. Ami Fukunaga
  5. Shohei Yamamoto
  6. Akihito Tanaka
  7. Kouki Matsuda
  8. Moto Kimura
  9. Kenji Maeda
  10. Gohzoh Ueda
  11. Tetsuya Mizoue
  12. Mugen Ujiie
  13. Hiroaki Mitsuya
  14. Norio Ohmagari
  15. Wataru Sugiura
  16. Katsushi Tokunaga

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Abstract

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ and CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017; Odd ratio (OR) 2.80, 95%confidence interval (CI) 1.05–7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2, while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95%CI 0.05–0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058; OR 0.42, 95%CI 0.15–1.16), B*52:01:01 (p = 0.031; OR 0.38, 95%CI 0.14–1.03), DQA1*03:02:01 (p = 0.028; OR 0.39, 95%CI 0.15–1.00) and DPB1*02:01:02 (p = 0.024; OR 0.45, 95%CI 0.21–0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

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  1. Version published to 10.3390/vaccines10040563
  2. ScreenIT

    SciScore for 10.1101/2022.02.01.22270285: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was approved by the Ethics Committee of the NCGM, Japan (approval number: NCGM-A-004175-00).
    Consent: Written informed consent was obtained from all participants prior to enrollment.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological assays: Antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit of the spike protein (IgG-S) (AdviseDx SARS-CoV-2 IgG II; Abbott, Chicago, IL) and SARS-CoV-2 nucleocapsid (IgG-N) (Abbott ARCHITECT® SARS-CoV-2 anti-N IgG; Abbott) were measured at each collection time point.
    S1 subunit of the spike protein (IgG-S
    suggested: None
    SARS-CoV-2 nucleocapsid (IgG-N
    suggested: None
    anti-N IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Serological assays: Antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit of the spike protein (IgG-S) (AdviseDx SARS-CoV-2 IgG II; Abbott, Chicago, IL) and SARS-CoV-2 nucleocapsid (IgG-N) (Abbott ARCHITECT® SARS-CoV-2 anti-N IgG; Abbott) were measured at each collection time point.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    The default analysis parameters and healthy metrics threshold were applied for TSV v2.0, while we applied the “ignore regions” function in NGSengine® to eliminate known sequencing error sites in the ion S5 system.
    NGSengine®
    suggested: None

    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

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  3. Version published to 10.1101/2022.02.01.22270285 on medRxiv