Humoral and T-Cell Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Ocrelizumab
Humoral and T-Cell Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Ocrelizumab
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DOI：
10.1001/jamaneurol.2021.3599
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发表时间：
2021-09-23
期刊：
影响因子：
29
通讯作者：
Vaknin-Dembinsky, Adi
中科院分区：
文献类型：
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作者：
Brill, Livnat;Rechtman, Ariel;Vaknin-Dembinsky, Adi
B细胞耗竭疗法可能影响疫苗接种后保护性免疫反应的发展。了解B细胞耗竭疗法治疗多发性硬化症（MS）患者对COVID-19产生疫苗特异性免疫的能力对临床决策具有重要意义。目的评估与健康对照组相比，ocrelizumab治疗患者的SARS-CoV-2疫苗特异性体液和细胞应答。设计、设置和参与者这项单中心研究在以色列耶路撒冷的哈达萨医学中心进行，包括接受ocrelizumab治疗的MS患者、健康对照和未经治疗的MS患者。疫苗接种发生在2020年12月至2021年4月之间。参与者在第二次疫苗接种后2 - 4周和2 - 8周分别献血用于抗体和T细胞评估。暴露所有参与者接受2次BNT 162 b2疫苗（Pfizer/BioNTech）并完成研究。主要结果和指标接种后接受ocrelizumab治疗的SARS-CoV-2特异性血清学和/或T细胞应答的患者比例。所有参与者都进行了SARS-CoV-2抗体检测; 29名接受ocrelizumab治疗的患者和15名健康对照者评估了SARS-CoV-2特异性T细胞应答。（43.8%）患有MS并接受ocrelizumab治疗（33例[67.3%]女性;平均[SD]年龄：47.9 [13.3]岁），23例（20.5%）患有MS，未接受疾病缓解治疗（18例[78.3%]女性;平均[SD]年龄，49 [13.4]岁），40例（35.7%）为健康对照（25例[62.5%]女性;平均[SD]年龄，45.3 [16]岁）。29名接受ocrelizumab治疗的患者中有26名（89.7%）和15名健康对照中的15名（100%）在接种疫苗后具有相似水平的SARS-CoV-2特异性T细胞（平均值[SD]分别为15.4 [7.6]和14.3 [6.3]斑点形成细胞）。ocrelizumab治疗组患者的平均抗体滴度和阳性血清学率较低（平均[SD]抗体滴度和阳性血清学率，26.2 [49.2]和376.5 [907.6] Au/mL;与健康对照组相比，S1/S2和受体结合结构域分别为10/40 [25%]和20/49 [40.8%]（平均[SD]抗体滴度和血清学阳性率分别为283 [100]和12 712 [9114] Au/mL; 100% S1/S2和受体结合结构域）和未经治疗的患者（平均[SD]抗体滴度和阳性血清学率，288.3 [113.8]和10 877 [9476] Au/mL; 100% S1/S2和受体结合结构域），与ocrelizumab输注时间呈正相关（S1/S2：r = 0.7，P <0.001;受体结合结构域：r = 0.4，P = 0.04）。结论和相关性在这项研究中，用ocrelizumab治疗的MS患者产生了与健康对照相当的SARS-CoV-2特异性T细胞应答，并且在接种疫苗后具有较低的抗体应答。考虑到T细胞在预防严重疾病中的潜在作用，这令人放心，并将有助于医生在COVID-19大流行时代制定关于MS治疗的共识指南。
IMPORTANCE B-cell-depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell-depleting therapy is of importance for clinical decisions.OBJECTIVE To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls.DESIGN, SETTING, AND PARTICIPANTS This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively.EXPOSURES All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study.MAIN OUTCOMES AND MEASURES Proportion of patients treated with ocrelizumab with SARS-CoV-2-specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2-specific T-cell responses.RESULTS Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2-specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04).CONCLUSION AND RELEVANCE In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regardingMS treatment in the era of the COVID-19 pandemic.