Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome

  1. Christoph Thurm
  2. Annegret Reinhold
  3. Katrin Borucki
  4. Sascha Kahlfuss
  5. Eugen Feist
  6. Jens Schreiber
  7. Dirk Reinhold
  8. Burkhart Schraven

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The COVID-19 pandemics has caused the death of almost six million people worldwide. In order to establish collective immunity, the first vaccines that were approved in Germany were the vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, respectively. As it was reported that SARS-CoV-2 can trigger autoimmunity, it is of significant interest to investigate whether COVID-19 vaccines evoke the formation of autoantibodies and subsequent autoimmunity. Here, we analyzed immune responses after different vaccination regimens (mRNA/mRNA, Vector/Vector or Vector/mRNA) with respect to anti-SARS-CoV-2-specific immunity and the development of autoantibodies well known for their appearance in distinct autoimmune diseases. We found that anti-SARS-CoV-2 antibody levels were 90% lower after Vector/Vector vaccination compared to the other vaccinations and that Vector/mRNA vaccination was more effective than mRNA/mRNA vaccination in terms of IgM and IgA responses. However, until 4 months after booster vaccination we only detected increases in autoantibodies in participants with already pre-existing autoantibodies whereas vaccinees showing no autoantibody formation before vaccination did not respond with sustained autoantibody production. Taken together, our study suggests that all used COVID-19 vaccines do not significantly foster the appearance of autoantibodies commonly associated with lupus erythematodes, rheumatoid arthritis, Celiac disease and antiphospholipid-syndrome but provide immunity to SARS-CoV-2.

Article activity feed

  1. Version published to 10.3390/vaccines10020333
  2. ScreenIT

    SciScore for 10.1101/2021.11.01.21265737: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Participants: The participants of this manuscript are from the CoVac study, which was approved by the ethics board of the Medical Faculty, Otto-von-Guericke University, Magdeburg (certificate 67/21) and registered with the Paul-Ehrlich-Institute, Langen, Germany (NIS613).
    Consent: After informed consent, we collected blood samples by venipuncture followed by serum collection.
    Sex as a biological variableParticipants consisted of 36% male and 64% female with a mean age of 36 years (20-65 years) for the mRNA/mRNA group, 47 years (24-69 years) for the Vector/Vector group and 38 years (19-66 years) for the Vector/mRNA group.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Quantification of Anti-SARS-CoV2-Sp1 antibodies: Quantification of anti-SARS-CoV2-Sp1-IgG antibodies was conducted using EliA SARS-CoV-2-Sp1 IgG test (ThermoFisher Scientific, Freiburg, Germany) according to manufacturer’s instructions.
    Anti-SARS-CoV2-Sp1
    suggested: None
    anti-SARS-CoV2-Sp1-IgG
    suggested: None
    ELISA: The presence of autoantibodies against cyclic citrullinated peptide (CCP, IgG; Medipan, Dahlewitz, Germany) and tissue transglutaminase (TTG, IgA; Generic Assays, Dahlewitz, Germany) were analyzed by ELISA according to the instructions of the manufacturer.
    CCP, IgG; Medipan, Dahlewitz, Germany
    suggested: None
    tissue transglutaminase (TTG, IgA; Generic Assays, Dahlewitz, Germany)
    suggested: None
    Quantifications of autoantibodies against Cardiolipin, Prothrombin and β2-Glycoprotein were conducted by ELISA using the Random Access Analyzer Alegria (Orgentec, Mainz, Germany) according to the manufacturer’s instructions.
    Cardiolipin, Prothrombin
    suggested: None
    The applied cutoffs were: anti-Cardiolipin-Screen ≥ 10 U/mL, anti-β2-Glycoprotein ≥ 10 U/mL, Prothrombin screen ≥ 20 U/mL. Immunofluorescence: Serum samples were screened for the presence of autoantibodies against nuclear antigens (ANA) using immunofluorescence with the ANA HEp-2 plus kit (Generic Assays, Dahlewitz, Germany) according to the manufacturer’s instructions.
    anti-Cardiolipin-Screen
    suggested: None
    anti-β2-Glycoprotein
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistics: Statistical analysis was performed using Prism8 (GraphPad, San Diego).
    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: 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.

  3. Version published to 10.1101/2021.11.01.21265737v1 on medRxiv