Ørbo Hilde S, de Matos Kasahara Taissa, Wolf Asia-Sophia, Bjørlykke Kristin H, Sexton Joseph, Jyssum Ingrid, Tveter Anne T, Solum Guri, Kjønstad Ingrid Fadum, Bhandari Sabin, Christensen Ingrid E, Kvien Tore K, Lind Andreas, Kared Hassen, Jahnsen Jørgen, Haavardsholm Espen A, Munthe Ludvig A, Provan Sella A, Vaage John T, Mjaaland Siri, Syversen Silje Watterdal, Jørgensen Kristin K, Grødeland Gunnveig, Goll Guro Løvik
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Lancet Reg Health Eur. 2024 Nov 15;48:101121. doi: 10.1016/j.lanepe.2024.101121. eCollection 2025 Jan.
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).
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.
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).
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.
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.
由于现在大多数人已获得混合免疫，免疫介导的炎症性疾病（IMID）患者是否需要定期接种更新的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗加强针尚不清楚。本研究的目的是评估肿瘤坏死因子抑制剂（TNFi）治疗的IMID患者接种第五剂二价疫苗后的体液和细胞免疫原性。
在纵向观察性的Nor-vaC研究中，我们评估了使用TNFi的有或无混合免疫的患者在接种第四剂单价疫苗和第五剂二价（BA.1或BA.4/5）疫苗后，针对武汉株、奥密克戎BA.1和BA.4的抗刺突中和抗体，以及反应性T细胞的频率和多功能性。
在2021年12月17日至2023年6月20日期间，456名未感染过新冠病毒且使用TNFi的IMID患者接种了第四剂疫苗，且在其他方面符合纳入标准。共有373/456（82%）的患者接种了第五剂疫苗，其中190/373（51%）具有混合免疫，定义为在第四剂和第五剂疫苗接种之间感染过新冠病毒。在具有混合免疫的患者中，与感染相比，第五剂疫苗并未诱导出更好的体液反应，无论是BA.1（抗刺突抗体浓度中位数23,244 IU/ml（四分位间距15,138 - 45,233）对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）。中和抗体的比较得出了类似结果。在未感染过新冠病毒的患者中，与第四剂疫苗（7304 IU/ml（3245 - 17,260），p < 0.0001）相比，第五剂BA.4/5疫苗诱导的体液反应略高（18,890 IU/ml（6494 - 50,211）），但BA.1疫苗没有。接种第四剂疫苗（刺突特异性细胞频率中位数0.039%（四分位间距0.010 - 0.14））、感染（0.058%（0.026 - 0.17））和第五剂疫苗后（0.058%（0.013 - 0.20）），CD8 T细胞反应保持稳定。
在具有混合免疫的TNFi治疗患者中，接种更新的第五剂SARS-CoV-2加强针没有免疫学益处。四剂疫苗后稳定的CD8细胞反应表明已建立保护性免疫。唯一风险因素为TNFi的患者未来可能遵循一般人群的疫苗接种建议。
挪威东南部地区卫生局、流行病防范创新联盟（CEPI）、迪阿科尼希门特医院、阿克什胡斯大学医院、奥斯陆大学医院、奥斯陆大学、挪威研究理事会。
