Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany.
Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Aliment Pharmacol Ther. 2023 Jan;57(1):103-116. doi: 10.1111/apt.17264. Epub 2022 Oct 28.
Immunosuppressed patients with inflammatory bowel disease (IBD) experience increased risk of vaccine-preventable diseases such as COVID-19.
To assess humoral and cellular immune responses following SARS-CoV-2 booster vaccination in immunosuppressed IBD patients and healthy controls.
In this prospective, multicentre, case-control study, 139 IBD patients treated with biologics and 110 healthy controls were recruited. Serum anti-SARS-CoV-2 spike IgG concentrations were measured 2-16 weeks after receiving a third mRNA vaccine dose. The primary outcome was to determine if humoral immune responses towards booster vaccines differ in IBD patients under anti-TNF versus non-anti-TNF therapy and healthy controls. Secondary outcomes were antibody decline, impact of previous infection and SARS-CoV-2-targeted T cell responses.
Anti-TNF-treated IBD patients showed reduced anti-spike IgG concentrations (geometric mean 2357.4 BAU/ml [geometric SD 3.3]) when compared to non-anti-TNF-treated patients (5935.7 BAU/ml [3.9]; p < 0.0001) and healthy controls (5481.7 BAU/ml [2.4]; p < 0.0001), respectively. In multivariable modelling, prior infection (geometric mean ratio 2.00 [95% CI 1.34-2.90]) and vaccination with mRNA-1273 (1.53 [1.01-2.27]) increased antibody concentrations, while anti-TNF treatment (0.39 [0.28-0.54]) and prolonged time between vaccination and antibody measurement (0.72 [0.58-0.90]) decreased anti-SARS-CoV-2 spike antibodies. Antibody decline was comparable in IBD patients independent of anti-TNF treatment and antibody concentrations could not predict breakthrough infections. Cellular and humoral immune responses were uncoupled, and more anti-TNF-treated patients than healthy controls developed inadequate T cell responses (15/73 [20.5%] vs 2/100 [2.0%]; p = 0.00031).
Anti-TNF-treated IBD patients have impaired humoral and cellular immunogenicity following SARS-CoV-2 booster vaccination. Fourth dose administration may be beneficial for these patients.
患有炎症性肠病（IBD）的免疫抑制患者患疫苗可预防疾病（如 COVID-19）的风险增加。
评估免疫抑制的 IBD 患者和健康对照者接受 SARS-CoV-2 加强疫苗接种后的体液和细胞免疫反应。
在这项前瞻性、多中心、病例对照研究中，招募了 139 名接受生物制剂治疗的 IBD 患者和 110 名健康对照者。在接受第三剂 mRNA 疫苗后 2-16 周测量血清抗 SARS-CoV-2 刺突 IgG 浓度。主要结局是确定在接受抗 TNF 治疗与非抗 TNF 治疗的 IBD 患者和健康对照者中，针对加强疫苗的体液免疫反应是否存在差异。次要结局是抗体下降、既往感染的影响和 SARS-CoV-2 靶向 T 细胞反应。
与非抗 TNF 治疗的患者（5935.7 BAU/ml [3.9]；p<0.0001）和健康对照者（5481.7 BAU/ml [2.4]；p<0.0001）相比，接受抗 TNF 治疗的 IBD 患者的抗刺突 IgG 浓度降低（几何均数 2357.4 BAU/ml [几何标准差 3.3]）。在多变量模型中，既往感染（几何均数比值 2.00 [95%CI 1.34-2.90]）和接种 mRNA-1273（1.53 [1.01-2.27]）增加了抗体浓度，而抗 TNF 治疗（0.39 [0.28-0.54]）和接种疫苗与抗体测量之间的时间延长（0.72 [0.58-0.90]）降低了抗 SARS-CoV-2 刺突抗体。在 IBD 患者中，抗体下降与抗 TNF 治疗无关，且抗体浓度不能预测突破性感染。细胞和体液免疫反应脱耦，接受抗 TNF 治疗的患者比健康对照者更易发生 T 细胞反应不足（15/73 [20.5%] 比 2/100 [2.0%]；p=0.00031）。
接受抗 TNF 治疗的 IBD 患者在接受 SARS-CoV-2 加强疫苗接种后，体液和细胞免疫原性受损。第四剂给药可能对这些患者有益。
