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免疫调节治疗患者中,有利于诱导 SARS-CoV-2 特异性 T 细胞应答的特征。

Favorable vaccine-induced SARS-CoV-2-specific T cell response profile in patients undergoing immune-modifying therapies.

机构信息

Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.

Department of Gastroenterology and Hepatology.

出版信息

J Clin Invest. 2022 Jun 15;132(12). doi: 10.1172/JCI159500.

Abstract

BACKGROUNDPatients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses.METHODSWe longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination.RESULTSWe demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile.CONCLUSIONDespite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection.FUNDINGThis study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

摘要

背景

接受免疫调节治疗的患者在 COVID-19 疫苗接种后表现出较低的体液反应,但我们缺乏对这些治疗方法对疫苗诱导的 T 细胞反应影响的适当评估。

方法

我们对接受免疫调节治疗(硫唑嘌呤或甲氨蝶呤)、TNF 抑制剂和/或其他生物治疗(抗整合素或抗 p40)的炎症性肠病(IBD)患者进行了长达 6 个月的随访,以纵向描述他们在完成 2 剂 COVID-19 mRNA 疫苗接种后的体液和刺突特异性 T 细胞反应。

结果

我们证明,在接受治疗的 IBD 患者中,不仅诱导了刺突特异性 T 细胞反应,其水平与健康个体相似,而且在接种后长达 6 个月内仍保持较高水平,特别是在接受 TNF 抑制剂治疗的患者中。此外,这些患者的刺突特异性 T 细胞反应主要针对 SARS-CoV-2 B.1.1.529(Omicron)中的突变保留下来,并表现出 Th1/IL-10 细胞因子特征。

结论

尽管存在体液反应缺陷,但接受免疫调节治疗的患者表现出有利的疫苗诱导 T 细胞反应特征,这仍可能为 COVID-19 提供一层保护。

资助

这项研究得到了国家传染病中心(NCID)催化计划(FY2021ES)和国家研究基金会竞争性研究计划(NRF-CRP25-2020-0003)的资助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7436/9197512/6015eb9c70bb/jci-132-159500-g197.jpg

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