Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
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DOI：
10.1016/j.ebiom.2021.103581
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发表时间：
2021-10
期刊：
影响因子：
11.1
通讯作者：
CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
中科院分区：
文献类型：
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作者：
Sormani MP;Inglese M;Schiavetti I;Carmisciano L;Laroni A;Lapucci C;Da Rin G;Serrati C;Gandoglia I;Tassinari T;Perego G;Brichetto G;Gazzola P;Mannironi A;Stromillo ML;Cordioli C;Landi D;Clerico M;Signoriello E;Frau J;Ferrò MT;Di Sapio A;Pasquali L;Ulivelli M;Marinelli F;Callari G;Iodice R;Liberatore G;Caleri F;Repice AM;Cordera S;Battaglia MA;Salvetti M;Franciotta D;Uccelli A;CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
在患有多发性硬化症（MS）的患者中，疾病修饰疗法（DMT）影响对抗原的免疫应答。因此，需要进行疫苗接种后血清学评估，以评估疫苗对SARS-CoV-2抗体应答的影响。我们设计了一项前瞻性多中心队列研究，招募了计划接种SARS-Cov-2 mRNA疫苗（BNT 162 b2，Pfizer/BioNTech，Inc或mRNA-1273，Moderna Tx，Inc）的患者。计划在首次疫苗接种前和第二次疫苗接种后4周采集血液，并进行集中血清学评估（电化学发光免疫分析，ECLIA，Roche-Diagnostics）。通过多变量线性回归分析抗体水平的对数转换。780只受试者（76% BNT 162 b2和24% mRNA-1273）接受了疫苗接种前和疫苗接种后4周的血液评估。87例（11.2%）未接受治疗，154例（19.7%）接受ocrelizumab治疗，25例（3.2%）接受利妥昔单抗治疗，85例（10.9%）接受芬戈莫德治疗，25例（3.2%）接受克拉屈滨治疗，404例（51.7%）接受其他DMT治疗。677名患者（86.8%）在接种疫苗后可检测到SARS-CoV-2抗体。在多变量分析中，与未治疗的患者相比，接受ocrelizumab（降低201倍（95%CI=128-317），p <0.001）、芬戈莫德（降低26倍（95%CI=16-42），p <0.001）和利妥昔单抗（降低20倍（95%CI=10-43），p <0.001）的患者的抗体水平显著降低。用mRNA-1273疫苗接种导致比用BNT 162 b2疫苗系统性地高3.25倍的抗体水平（95%CI= 2.46 - 4.27）（p <0.001）。抗CD 20治疗的抗体水平与自上次输注以来的时间相关，利妥昔单抗的间隔时间（平均值=386天）长于ocrelizumab患者（平均值=129天）。在SARS-CoV-2中，抗CD 20治疗和芬戈莫德导致对基于mRNA的SARS-CoV-2疫苗的体液应答降低。由于mRNA-1273激发的抗体水平比BNT 162 b2高3.25倍，因此可以优先考虑将该疫苗用于接受抗CD 20治疗或芬戈莫德治疗的患者。将我们的数据与对疫苗的细胞免疫反应的数据相结合，包括临床随访，将有助于在DMT和MS的背景下更好地定义最合适的SARS-CoV-2疫苗策略。FISM[2021/Special-Multi/001];意大利卫生部“Progetto Z 844 A 5 × 1000”。
In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128–317), p < 0·001), fingolimod (26-fold decrease (95%CI=16–42), p < 0·001) and rituximab (20-fold decrease (95%CI=10–43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46–4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days). In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. FISM[2021/Special-Multi/001]; Italian Ministry of Health‘Progetto Z844A 5 × 1000′.
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DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
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作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
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C4591001 Clinical Trial Group
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DOI：
10.1007/s10096-021-04169-7
发表时间：
2021-05
期刊：
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子：
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作者：
Müller L;Ostermann PN;Walker A;Wienemann T;Mertens A;Adams O;Andree M;Hauka S;Lübke N;Keitel V;Drexler I;Di Cristanziano V;Hermsen DF;Kaiser R;Boege F;Klein F;Schaal H;Timm J;Senff T
通讯作者：
Senff T
影响因子：
24.8
作者：
Saini SK;Hersby DS;Tamhane T;Povlsen HR;Amaya Hernandez SP;Nielsen M;Gang AO;Hadrup SR
通讯作者：
Hadrup SR
影响因子：
5.9
作者：
Achiron A;Mandel M;Dreyer-Alster S;Harari G;Magalashvili D;Sonis P;Dolev M;Menascu S;Flechter S;Falb R;Gurevich M
通讯作者：
Gurevich M
影响因子：
13.6
作者：
Lacson, Eduardo, Jr.;Argyropoulos, Christos P.;Weiner, Daniel E.
通讯作者：
Weiner, Daniel E.