Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway.
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
EBioMedicine. 2024 Oct;108:105317. doi: 10.1016/j.ebiom.2024.105317. Epub 2024 Sep 10.
BACKGROUND: Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. METHODS: This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2-4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. FINDINGS: Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. INTERPRETATION: Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines. FUNDING: South-Eastern Norway Regional Health Authority, Coalition for Epidemic Preparedness Innovations (CEPI), Norwegian Institute of Public Health, Akershus University Hospital, Diakonhjemmet Hospital.
背景：了解细胞对 SARS-CoV-2 免疫接种的反应对于在接受免疫抑制治疗的炎症性肠病（IBD）患者和其他易感患者中为疫苗接种提供建议非常重要。本研究调查了多次 SARS-CoV-2 疫苗接种和 COVID-19 突破性感染后 T 细胞反应的幅度和质量。
方法：本前瞻性观察性研究纳入了接受肿瘤坏死因子抑制剂（TNFi）治疗的 IBD 和关节炎患者，他们接受了多达四剂 SARS-CoV-2 疫苗。在接种疫苗和突破性感染后 2-4 周，通过流式细胞术测量针对 SARS-CoV-2 肽的 T 细胞反应，以评估反应细胞的频率和多功能性，以及受体结合域（anti-RBD）抗体。
结果：2021 年 3 月 2 日至 2022 年 12 月 20 日期间，共纳入 143 名患者（118 名 IBD，25 名关节炎）和 73 名健康对照者。与健康对照者相比，IBD 或关节炎患者在接受三剂 SARS-CoV-2 疫苗后，体液免疫反应减弱（中位数抗-RBD 水平分别为 3391 与 6280 BAU/ml，p=0.008）。IBD 患者的 CD4 数量（中位数 0.11%比 0.11%，p=0.26）和 CD8 数量（中位数 0.031%比 0.047%，p=0.33）和质量（多功能性评分：0.403 比 0.371，p=0.39；0.105 比 0.101，p=0.87）与健康对照者相当。关节炎患者的反应性 T 细胞频率较低，但与对照组相比质量相当。突破性感染增加了针对刺突蛋白的 CD8 T 细胞质量和针对非刺突肽的 T 细胞反应。
解释：尽管 TNFi 治疗的 IBD 患者在接受三剂疫苗后出现了体液免疫反应减弱的情况，但他们仍具有 T 细胞反应，与健康对照组相当。重复接种疫苗和突破性感染增加了 T 细胞反应的质量。我们的研究提供了证据表明，在没有其他危险因素的情况下，该人群在未来可能能够遵循 COVID-19 疫苗的一般建议。
经费：挪威东南地区卫生局、流行病防范创新联盟（CEPI）、挪威公共卫生研究所、阿克什胡斯大学医院、迪翁赫姆医院。
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