在接受疾病修正治疗的多发性硬化症患者中，混合免疫对 SARS-CoV-2 疫苗接种后免疫反应的影响。
The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies.
机构信息
Therapeutic Immune Design, Department of Clinical Neuroscience, Center for Molecular Medicine L8:02, Karolinska Institute, Stockholm, Sweden.
Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine L8:04, Karolinska Institute, Stockholm, Sweden.
出版信息
Eur J Neurol. 2023 Dec;30(12):3789-3798. doi: 10.1111/ene.16015. Epub 2023 Aug 24.
BACKGROUND AND PURPOSE
Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection.
METHODS
Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13).
RESULTS
Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine.
CONCLUSION
These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.
背景与目的
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的混合免疫是由自然感染和疫苗产生的免疫共同作用形成的。多发性硬化症（MS）的疾病修正治疗（DMT）有可能影响 SARS-CoV-2 疫苗接种和感染引起的体液和细胞免疫。本研究旨在比较不同 DMT 治疗的 MS 患者（pwMS）接种 SARS-CoV-2 mRNA 疫苗后的抗体和 T 细胞反应，并评估未经 SARS-CoV-2 感染初次接种疫苗的 pwMS 和先前 SARS-CoV-2 感染后接种疫苗的 pwMS 之间的差异。
方法
在 143 名 pwMS 中，我们在接受或未接受 SARS-CoV-2 感染的情况下，检测了基线和接种 SARS-CoV-2 疫苗第二针后 4 周和 12 周时的抗体和 T 细胞反应，其中 40 名为健康对照（HCs）。MS 队列包括那他珠单抗（n=22）、二甲基富马酸（n=23）、芬戈莫德（n=38）、克拉屈滨（n=30）、阿仑单抗（n=17）和特立氟胺（n=13）治疗的 pwMS。使用多重珠粒分析测定 SARS-CoV-2 抗原的 IgG 抗体反应，并用 FluoroSpot 测定 T 细胞反应（干扰素 γ 和白细胞介素 13）。
结果
初次接种疫苗的 HCs 和接受那他珠单抗、二甲基富马酸、克拉屈滨、阿仑单抗和特立氟胺治疗的 pwMS 的体液和 T 细胞对疫苗的反应相似，但在接受芬戈莫德治疗的 pwMS 中受到抑制。与初次接种疫苗的个体相比，先前感染 SARS-CoV-2 后接种疫苗的芬戈莫德治疗的 pwMS 和 HCs 在接种疫苗后 4 周时抗体水平更高。接种疫苗后 12 周时的抗体和干扰素 γ 水平与克拉屈滨最后一次治疗疗程的时间呈正相关。
结论
这些发现与 pwMS 接受 DMT 时的感染风险降低和疫苗接种策略有关。
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