使用肿瘤坏死因子抑制剂的免疫介导炎症性疾病患者对第五剂二价 SARS-CoV-2 疫苗的体液和细胞反应：一项前瞻性队列研究

IF 13.6 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Europe Pub Date : 2024-11-15 DOI:10.1016/j.lanepe.2024.101121

Hilde S. Ørbo , Taissa de Matos Kasahara , Asia-Sophia Wolf , Kristin H. Bjørlykke , Joseph Sexton , Ingrid Jyssum , Anne T. Tveter , Guri Solum , Ingrid Fadum Kjønstad , Sabin Bhandari , Ingrid E. Christensen , Tore K. Kvien , Andreas Lind , Hassen Kared , Jørgen Jahnsen , Espen A. Haavardsholm , Ludvig A. Munthe , Sella A. Provan , John T. Vaage , Siri Mjaaland , Guro Løvik Goll

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引用次数: 0

摘要

背景由于目前大多数人已经建立了混合免疫，因此免疫介导的炎症性疾病（IMID）患者是否需要定期接种新的SARS-CoV-2疫苗尚不清楚。研究的目的是评估使用肿瘤坏死因子抑制剂（TNFi）的 IMID 患者接种第五剂二价疫苗的体液和细胞免疫原性、研究结果在 2021 年 12 月 17 日至 2023 年 6 月 20 日期间，456 名使用 TNFi 的 IMIDs 感染免疫失败患者接受了第四剂疫苗和第五剂二价疫苗（BA.1 或 BA.4/5），并符合纳入条件。共有373/456人（82%）接种了第五剂疫苗，其中190/373人（51%）获得了混合免疫，混合免疫的定义是在第四剂和第五剂之间接种过COVID-19。在具有混合免疫力的患者中，与感染相比，第五剂疫苗并未改善体液反应，无论是 BA.1（抗尖峰抗体浓度中位数 23,244 IU/ml (IQR 15,138-45,233) vs 36,341 IU/ml (11,887-53,710)，p = 0.52）还是 BA.4/5（31,693 IU/ml (15,176-54,186)，p = 0.30）。中和抗体的比较结果类似。与第四剂疫苗（7304 IU/ml (3245-17,260), p < 0.0001）相比，在感染免疫患者中，第五剂 BA.4/5 疫苗（而非 BA.1）诱导的体液反应略高（18890 IU/ml (6494-50,211) ）。CD8 T细胞反应在第四剂（尖峰特异性细胞频率中位数为0.039% (IQR 0.010-0.14)）、感染（0.058% (0.026-0.17)）和第五剂（0.058% (0.013-0.20)）后保持稳定。四次加强剂量后稳定的CD8细胞反应表明保护性免疫已经建立。挪威东南部地区卫生局、流行病防备创新联盟（CEPI）、Diakonhjemmet医院、阿克苏斯大学医院、奥斯陆大学医院、奥斯陆大学、挪威研究理事会。

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Humoral and cellular responses to a fifth bivalent SARS-CoV-2 vaccine dose in patients with immune-mediated inflammatory diseases on tumour necrosis factor inhibitors: a prospective cohort study

Background

As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi).

Methods

In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi.

Findings

Between December 17, 2021, and June 20, 2023, 456 infection-naïve patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138–45,233) vs 36,341 IU/ml (11,887–53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176–54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naïve patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494–50,211)) compared to the fourth dose (7304 IU/ml (3245–17,260), p < 0.0001). CD8 T cell responses remained stable following a fourth dose (median frequency of spike-specific cells 0.039% (IQR 0.010–0.14)), infection (0.058% (0.026–0.17)) and a fifth dose (0.058% (0.013–0.20).

Interpretation

In patients on TNFi with hybrid immunity, there was no immunological benefit of an updated fifth SARS-CoV-2 booster dose. Stable CD8 cellular responses following four doses indicate established protective immunity. Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population.

Funding

The South-Eastern Norway Regional Health Authority, The Coalition for Epidemic Preparedness Innovations (CEPI), Diakonhjemmet Hospital, Akershus University Hospital, Oslo University Hospital, University of Oslo, The Norwegian Research Council.

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.