In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.

This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens.

Among 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred.

In this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable.

对于多发性硬化症 (pwMS) 患者，担心疾病可能恶化或引发其他自身免疫性疾病，会导致他们对疫苗犹豫不决。我们评估了 mRNA 疫苗接种后对 SARS-CoV-2 的体液和 T 细胞反应、疾病活动的变化以及针对中枢或外周神经系统抗原的抗体的产生。

这是一项为期 1 年的前瞻性纵向观察研究，研究对象为 pwMS 和接受 mRNA 疫苗的其他炎症性神经系统疾病 (OIND) 患者的对照组。在第一次给药前 (T1)、第一次给药后 1 个月 (T2)、第二次给药后 1 个月 (T3) 以及给药后 6 (T4)、9 (T5) 和 12 (T6) 个月采集血样第一剂。对患者的免疫特异性反应、年复发率（ARR）以及肿瘤神经元、神经表面、神经胶质、神经节苷脂和结节旁抗原的抗体进行评估。

在研究的 454 名患者中，390 名患有 MS（22 名青少年），64 名患有 OIND；平均 (SD) 年龄为 44 (14) 岁；315 名（69%）为女性；392 人 (87%) 正在接受疾病缓解疗法。T3 时有 367 名患者（86%）检测到了受体结合结构域的抗体，T4 时有 276 名患者（83%）检测到了受体结合域的抗体。第三次注射后，60 名血清阴性患者中只有 13 名（22%）发生血清转化，255 名（92%）在 T6 时仍保持血清阳性。T3 时有 381 名 (93%) 患者出现细胞反应，T6 时有 235 名 (91%) 患者出现细胞反应，其中包括所有接受抗 CD20 治疗的患者和 79% 接受芬戈莫德治疗的患者。在 T3（429 名患者）或 T6（395 名患者）时，没有患者出现 CNS 自身抗体。7 名患者在免疫前已存在神经抗体（3 名成年 MS 患者有 MOG-IgG，2 名 MG 患者和 1 名 MS 患者有神经元细胞表面抗体 [未知抗原]，1 名 MS 患者有髓磷脂抗体反应性 [未知抗原] ]。同样，在 T3（427 名患者）时没有发现针对 PNS 抗原的抗体。MS 中的 ARR 较低，而 OIND 患者中没有显着差异。虽然 182 名（40%）患者出现 SARS-CoV-2 感染，但没有病例发生严重的 COVID-19 或严重的不良事件。

在这项研究中，mRNA COVID-19 疫苗接种是安全的，不会加剧自身免疫性疾病，也不会引发神经自身抗体或免疫介导的神经系统疾病。感染 SARS-CoV-2 的患者预后良好。