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接受达利珠单抗治疗的多发性硬化症患者对流感疫苗可产生正常的免疫应答。

Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.

机构信息

Neuroimmunological Diseases Unit, Neuroimmunology Branch (Y.C.L., P.W., A.B., E.R., B.B.) and Clinical Neuroscience Program (T.W.), National Institute of Neurological Diseases and Stroke, NIH, Bethesda, MD; FDA (J.M., L.R.K., H.G.), CBER; and NIH Center for Human Immunology (B.B.), NIH, Bethesda, MD.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2016 Jan 27;3(1):e196. doi: 10.1212/NXI.0000000000000196. eCollection 2016 Feb.

Abstract

OBJECTIVE

The purpose of this study was to assess the potential immunosuppressive role of daclizumab, a humanized monoclonal antibody against the α chain of the interleukin 2 receptor, in vivo, by comparing immune responses to the 2013 seasonal influenza vaccination between patients with multiple sclerosis (MS) on long-term daclizumab therapy and controls.

METHODS

Previously defined subpopulations of adaptive immune cells known to correlate with the immune response to the influenza vaccination were evaluated by 12-color flow cytometry in 23 daclizumab-treated patients with MS and 14 MS or healthy controls before (D0) and 1 day (D1) and 7 days (D7) after administration of the 2013 Afluria vaccine. Neutralizing antibody titers and CD4(+), CD8(+) T cell, B cell, and natural killer cell proliferation to 3 strains of virus contained in the Afluria vaccine were assessed at D0, D7, and 180 days postvaccination.

RESULTS

Daclizumab-treated patients and controls demonstrated comparable, statistically significant expansions of previously defined subpopulations of activated CD8(+) T cells and B cells that characterize the development of effective immune responses to the influenza vaccine, while proliferation of T cells to influenza and control antigens was diminished in the daclizumab cohort. All participants fulfilled FDA criteria for seroconversion or seroprotection in antibody assays.

CONCLUSION

Despite the mild immunosuppressive effects of daclizumab in vivo demonstrated by an increased incidence of infectious complications in clinical trials, patients with MS under daclizumab therapy mount normal antibody responses to influenza vaccinations.

摘要

目的

本研究旨在通过比较多发性硬化症(MS)患者在长期接受达珠单抗治疗与对照组之间对 2013 年季节性流感疫苗的免疫反应,评估达珠单抗(一种针对白细胞介素 2 受体α链的人源化单克隆抗体)的潜在免疫抑制作用。

方法

通过 12 色流式细胞术,对 23 例接受达珠单抗治疗的 MS 患者和 14 例 MS 或健康对照者在接种 2013 年 Afluria 疫苗前(D0)、1 天(D1)和 7 天(D7)时,对已知与流感疫苗免疫反应相关的适应性免疫细胞亚群进行了评估。在接种疫苗后第 0 天(D0)、第 7 天(D7)和第 180 天,评估了针对 Afluria 疫苗中包含的 3 种病毒的中和抗体滴度以及 CD4(+)、CD8(+)T 细胞、B 细胞和自然杀伤细胞的增殖。

结果

达珠单抗治疗的患者和对照组表现出可比较的、统计学显著的、以前定义的激活 CD8(+)T 细胞和 B 细胞亚群的扩增,这些亚群的特征是对流感疫苗产生有效的免疫反应,而 T 细胞对流感和对照抗原的增殖在达珠单抗组中被减弱。所有参与者在抗体检测中均符合 FDA 对血清转换或血清保护的标准。

结论

尽管在临床试验中达珠单抗具有轻微的免疫抑制作用,导致感染并发症的发生率增加,但接受达珠单抗治疗的 MS 患者对流感疫苗产生正常的抗体反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd5c/4733151/60eba809b5fe/NEURIMMINFL2015006908FF1.jpg

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