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.

Coronavirus 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).