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不同 COVID-19 疫苗引发的免疫反应的复杂性,考虑到天然自身抗体和免疫调节疗法。

Complexity of the Immune Response Elicited by Different COVID-19 Vaccines, in the Light of Natural Autoantibodies and Immunomodulatory Therapies.

机构信息

Department of Immunology and Biotechnology, Clinical Center, University of Pécs Medical School, 7624 Pécs, Hungary.

Department of Dermatology, Venereology and Oncodermatology, Clinical Center, University of Pécs Medical School, 7624 Pécs, Hungary.

出版信息

Int J Mol Sci. 2023 Mar 29;24(7):6439. doi: 10.3390/ijms24076439.

DOI:10.3390/ijms24076439
PMID:37047412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10094397/
Abstract

Despite the abundance of data on the COVID-19 vaccine-induced immune activation, the impact of natural autoantibodies (nAAbs) on these processes is less well defined. Therefore, we investigated potential connections between vaccine efficacy and nAAb levels. We were also interested in the impact of immunomodulatory therapies on vaccine efficacy. Clinical residual samples were used for the assessment of the COVID-19 vaccine-elicited immune response (IR) (n=255), as well as for the investigation of the immunization-associated expansion of the nAAb pool (n=185). In order to study the potential interaction between immunomodulatory therapies and the vaccine-induced IR, untreated, healthy individuals and patients receiving anti-TNFα or anti-IL-17 therapies were compared (n total =45). In-house ELISAs (anticitrate synthase, anti-HSP60 and-70) and commercial ELISAs (anti-SARS-CoV-2 ELISAs IgG, IgA, NeutraLISA and IFN-γ release assay 'IGRA') were applied. We found significant differences in the IR given to different vaccines. Moreover, nAAb levels showed plasticity in response to anti-COVID-19 immunization. We conclude that our findings may support the theorem about the non-specific beneficial 'side effects' of vaccination, including the broadening of the nAAb repertoire. Considering immunomodulation, we suggest that anti-TNFα and anti-IL17 treatments may interfere negatively with MALT-associated IR, manifested as decreased IgA titers; however, the modest sample numbers of the herein presented model might be a limiting factor of reaching a more comprehensive conclusion.

摘要

尽管有大量关于 COVID-19 疫苗诱导免疫激活的数据,但自然自身抗体(nAAb)对这些过程的影响还不太明确。因此,我们研究了疫苗疗效和 nAAb 水平之间的潜在联系。我们还对免疫调节疗法对疫苗疗效的影响感兴趣。临床残留样本用于评估 COVID-19 疫苗引起的免疫反应(IR)(n=255),并用于研究免疫接种引起的 nAAb 池扩张(n=185)。为了研究免疫调节疗法与疫苗诱导的 IR 之间的潜在相互作用,我们比较了未治疗的健康个体和接受抗 TNF-α或抗 IL-17 治疗的患者(n 总=45)。应用了内部 ELISA(抗瓜氨酸合成酶、抗 HSP60 和-70)和商业 ELISA(抗 SARS-CoV-2 ELISA IgG、IgA、NeutralISA 和 IFN-γ释放测定'IGRA')。我们发现,不同疫苗引起的 IR 存在显著差异。此外,nAAb 水平对抗 COVID-19 免疫接种表现出可塑性。我们得出结论,我们的发现可能支持关于疫苗非特异性有益“副作用”的理论,包括扩大 nAAb 库。考虑到免疫调节,我们建议抗 TNF-α和抗 IL17 治疗可能会对与 MALT 相关的 IR 产生负面影响,表现为 IgA 滴度降低;然而,本模型中呈现的样本数量较少可能是得出更全面结论的限制因素。

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