University of Connecticut, School of Nursing, Storrs, Connecticut, USA.
Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
J Med Virol. 2023 Oct;95(10):e29137. doi: 10.1002/jmv.29137.
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).
新型冠状病毒疾病 2019（COVID-19）疫苗具有高度的有效性，但也会引起不良反应，特别是自身免疫。几项研究的结果表明，患有危及生命的 SARS-CoV-2 感染的患者对 I 型干扰素（IFN）具有增加的、预先存在的中和抗体。然而，COVID-19 疫苗接种是否会诱导抗 I 型 IFN 抗体尚不清楚。在本研究中，我们评估了健康个体在 COVID-19 疫苗接种前后血浆中针对各种人类自身抗原的 103 种自身抗体和针对病毒抗原的 16 种抗体的水平。12 名参与者接受了 COVID-19 mRNA 疫苗（辉瑞-生物科技或 Moderna），8 名参与者接受了基于病毒载体的疫苗（杨森）。所有参与者在接种疫苗后均产生了针对 SARS-CoV-2 抗原的抗体水平增加。在 103 种自身抗体中，只有接受 mRNA 疫苗（3/12）的参与者的针对 I 型 IFN 的 IgG 自身抗体的血浆水平在接种后增加，而接受基于病毒载体的疫苗（0/8）的参与者则没有增加。在接种疫苗后显示 IgG 抗 IFN 增加的三个人中，两种血浆样本和血浆纯化的总 IgGs 均显示出剂量依赖性结合 IFN-α的能力；三个人中的两个人在接种疫苗后比体外基线更能中和 IFN-α-2a 诱导的人外周血单核细胞中磷酸化 STAT1 反应的活性。在测试的 103 种自身抗体中，COVID-19 mRNA 疫苗，但不是基于病毒载体的疫苗，在一小部分健康个体（约 10%）中特异性诱导了针对 I 型 IFN 的中和自身抗体。本研究的结果表明，COVID-19 mRNA 疫苗可能会通过诱导某些健康个体的自身免疫来抑制 IFN 介导的先天免疫并损害免疫防御，这些个体可能需要改用另一种 COVID-19 疫苗（例如，基于病毒载体的疫苗）。
