多发性硬化症患者和健康对照者对 SARS-CoV-2 第三次接种的体液免疫反应：一项前瞻性多中心研究。
Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study.
机构信息
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
出版信息
Mult Scler Relat Disord. 2022 Sep;65:104009. doi: 10.1016/j.msard.2022.104009. Epub 2022 Jul 2.
BACKGROUND
Third vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination.
METHODS
In this prospective multicenter study on 292 pwMS and 46 healthy controls (HC), who had all received two vaccinations prior to study enrollment, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after third vaccination. PwMS were categorized as follows: untreated (N-DMT, n = 32), receiving disease-modifying therapy (DMT) with expected humoral response (er-DMT: interferon-beta preparations, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, cladribine, alemtuzumab; n = 120) or no expected humoral response (nr-DMT: S1PMs, CD20mAb; n = 140).
RESULTS
PwMS on nr-DMT had significantly lower median antibody levels before (12.1 U/ml [0.4-2500]) and after third vaccination (305 U/ml [0.4-2500]) in comparison to other groups (p<0.001). We did not find differences in antibody levels after homologous (n = 281; 2500 [0.4-2500]) and heterologous (n = 57; 2500 [0.4-2500]) vaccination regime regardless of the DMT group. The DMT group (β= -0.60; 95% CI -1195.73, -799.10; p<0.001) was associated with antibody levels after third vaccination, while time to revaccination (6 months [1-13]) was not. After third vaccination, seropositivity was reached in 75.8% and 82.2% of pwMS on anti-CD20 mAbs and S1PMs, respectively. Complete B-cell depletion significantly decreased the probability of seroconversion even after the third vaccination (OR 0.14; p = 0.021), whereas time interval to last DMT intake and time to revaccination did not. Twenty-two patients reported a SARS-CoV-2 infection (3 N-DMT, 9 er-DMT, 10 nr-DMT), one being asymptomatic and the rest having a mild course.
CONCLUSION
Humoral response to SARS-CoV-2 third vaccination in pwMS is excellent. While reduced by S1PMs and CD20mAb, protective response is still expected in the majority of patients.
背景
建议多发性硬化症（pwMS）患者在最后一次接种疫苗后 6 个月进行第三次 SARS-CoV-2 疫苗接种。
方法
在这项针对 292 名 pwMS 和 46 名健康对照者（HC）的前瞻性多中心研究中，所有参与者在研究入组前均已接受了两次接种，在第三次接种前一个月和接种后 2-4 个月测量了 SARS-CoV-2 IgG 反应。pwMS 分为以下几类：未治疗（N-DMT，n=32）、接受预期有体液反应的疾病修正疗法（DMT）（er-DMT：干扰素-β制剂、格拉替雷、二甲基富马酸、特立氟胺、那他珠单抗、克拉屈滨、阿仑单抗；n=120）或无预期体液反应的（nr-DMT：S1PMs、CD20mAb；n=140）。
结果
与其他组相比（p<0.001），接受 nr-DMT 的 pwMS 在第三次接种前（中位数为 12.1 U/ml[0.4-2500]）和接种后（中位数为 305 U/ml[0.4-2500]）的抗体水平明显较低。我们发现无论 DMT 组如何，同源（n=281；2500[0.4-2500]）和异源（n=57；2500[0.4-2500]）接种方案后的抗体水平均无差异。DMT 组（β=-0.60；95%CI-1195.73，-799.10；p<0.001）与第三次接种后的抗体水平相关，而接种时间（6 个月[1-13]）则不相关。第三次接种后，抗 CD20mAb 和 S1PMs 治疗的 pwMS 中分别有 75.8%和 82.2%达到血清阳性。完全 B 细胞耗竭即使在第三次接种后也显著降低了血清转化率的可能性（OR 0.14；p=0.021），而上次 DMT 摄入时间和接种时间间隔则没有。22 名患者报告了 SARS-CoV-2 感染（3 名 N-DMT、9 名 er-DMT、10 名 nr-DMT），1 名无症状，其余患者症状较轻。
结论
pwMS 对 SARS-CoV-2 第三次疫苗接种的体液反应良好。虽然 S1PMs 和 CD20mAb 会降低反应，但大多数患者仍有望产生保护反应。
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