COVID‐19 mRNA vaccine, but not a viral vector‐based vaccine, promotes neutralizing anti‐type I interferon autoantibody production in a small group of healthy individuals

Abstract

AbstractCoronavirus disease 2019 (COVID‐19) vaccines are highly effective but also induce adverse events, in particular, autoimmunity. Findings from several studies revealed that patients with life‐threatening SARS‐CoV‐2 infection had increased, pre‐existing, neutralizing antibodies against type I interferons (IFNs). However, whether COVID‐19 vaccination induces the anti‐type I IFN antibody remains unclear. In the current study, we evaluated plasma levels of 103 autoantibodies against various human self‐antigens and 16 antibodies against viral antigens in healthy individuals pre‐ and post‐COVID‐19 vaccination. Twelve participants received a COVID‐19 mRNA vaccine (Pfizer‐BioNTech or Moderna), and 8 participants received a viral vector‐based vaccine (Janssen). All participants produced increased antibody levels against SARS‐CoV‐2 antigens following vaccination. Among the 103 autoantibodies, only plasma levels of IgG autoantibodies against type I IFNs increased in participants who received a mRNA vaccine (3/12), but not in those who received the viral vector‐based vaccine (0/8) at postvaccination compared to pre‐vaccination. Among the three individuals showing increased anti‐IFN IgG following vaccination, both plasma samples and plasma‐purified total IgGs showed a dose‐dependent binding ability to IFN‐α; two of the three showed neutralizing activity to IFN‐α‐2a‐induced phosphorated STAT1 responses in human peripheral blood mononuclear cells postvaccination compared to baseline in vitro. Among the 103 autoantibodies tested, the COVID‐19 mRNA vaccine, but not the viral vector‐based vaccine, specifically induced neutralizing anti‐type I IFN autoantibodies in a small group of healthy individuals (~10%). Findings from this study imply that COVID‐19 mRNA vaccines may suppress IFN‐mediated innate immunity and impair immune defense through induced autoimmunity in some healthy individuals, who may need to switch to another type of COVID‐19 vaccine (e.g., a viral vector‐based vaccine).