奥瑞珠单抗或芬戈莫德治疗多发性硬化症患者第三次接种 SARS-CoV-2 疫苗后的纵向 T 细胞反应。
Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis on Ocrelizumab or Fingolimod.
机构信息
From the Department of Immunopathology (V.P.C., L.Y.L.K., M.D., V.A.L.K., N.J.M.V., M.S., T.R., G.W., S.M.v.H., A.t.B.), Sanquin Research and Landsteiner Laboratory, Amsterdam UMC; Department of Neurology and Neurophysiology (L.K., L.W., K.P.J.v.D., E.W.S., F.E.), Amsterdam Neuroscience, Amsterdam UMC, location AMC, University of Amsterdam; Department of Hematopoiesis (R.R.H., C.E.v.d.S.), Sanquin Research and Landsteiner Laboratory, Amsterdam UMC; Department of Experimental Immunohematology (R.R.H.), Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Department of Microbiology and Immunology (C.E.v.d.S.), University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Amsterdam Rheumatology and Immunology Center (L.B., G.W.), location Reade, Department of Rheumatology; Amsterdam Rheumatology and Immunology Center (S.W.T.), Amsterdam UMC, Department of Rheumatology and Clinical Immunology, University of Amsterdam; Department of Neurology (J.K., Z.L.E.v.K.), Amsterdam UMC, Vrije Universiteit; Department 32 of Pediatric Immunology (T.W.K.), Rheumatology and Infectious Disease, Amsterdam UMC, location AMC, University of Amsterdam; and Swammerdam Institute for Life Sciences (S.M.v.H.), University of Amsterdam, the Netherlands.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 May 6;9(4). doi: 10.1212/NXI.0000000000001178. Print 2022 Jul.
OBJECTIVES
To evaluate whether a third vaccination shows an added effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell responses in patients with multiple sclerosis treated with ocrelizumab or fingolimod.
METHODS
This is a substudy of a prospective multicenter study on SARS-CoV-2 vaccination in patients with immune-mediated diseases. Patients with MS treated with ocrelizumab, fingolimod, and no disease-modifying therapies and healthy controls were included. The number of interferon (IFN)-γ secreting SARS-CoV-2-specific T cells at multiple time points before and after 3 SARS-CoV-2 vaccinations were evaluated.
RESULTS
In ocrelizumab-treated patients (N = 24), IFN-γ-producing SARS-CoV-2-specific T-cell responses were induced after 2 vaccinations with median levels comparable to healthy controls (N = 12) and patients with MS without disease-modifying therapies (N = 10). A third vaccination in ocrelizumab-treated patients (N = 8) boosted T-cell responses that had declined after the second vaccination, but did not lead to higher overall T-cell responses as compared to immediately after a second vaccination. In fingolimod-treated patients, no SARS-CoV-2-specific T cells were detected after second (N = 12) and third (N = 9) vaccinations.
DISCUSSION
In ocrelizumab-treated patients with MS, a third SARS-CoV-2 vaccination had no additive effect on the maximal T-cell response but did induce a boost response. In fingolimod-treated patients, no T-cell responses could be detected following both a second and third SARS-CoV-2 vaccination.
目的
评估在接受奥瑞珠单抗或芬戈利莫德治疗的多发性硬化症患者中，第三次接种是否对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）T 细胞反应有额外作用。
方法
这是一项关于免疫介导性疾病患者 SARS-CoV-2 疫苗接种的前瞻性多中心研究的子研究。纳入接受奥瑞珠单抗、芬戈利莫德和无疾病修正治疗的 MS 患者以及健康对照者。评估了 3 次 SARS-CoV-2 接种前后多个时间点 IFN-γ 分泌 SARS-CoV-2 特异性 T 细胞的数量。
结果
在奥瑞珠单抗治疗的患者（N=24）中，2 次接种后诱导了 IFN-γ 产生的 SARS-CoV-2 特异性 T 细胞反应，其中位数水平与健康对照者（N=12）和无疾病修正治疗的 MS 患者（N=10）相当。在奥瑞珠单抗治疗的患者（N=8）中进行第三次接种可增强第二次接种后下降的 T 细胞反应，但与第二次接种后即刻相比，并未导致总体 T 细胞反应更高。在芬戈利莫德治疗的患者中，第二次（N=12）和第三次（N=9）接种后均未检测到 SARS-CoV-2 特异性 T 细胞。
讨论
在接受奥瑞珠单抗治疗的 MS 患者中，第三次 SARS-CoV-2 接种对最大 T 细胞反应没有附加作用，但确实诱导了增强反应。在接受芬戈利莫德治疗的患者中，第二次和第三次 SARS-CoV-2 接种后均未检测到 T 细胞反应。
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