Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.
Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.
复制标题
DOI：
10.1038/s41591-021-01507-2
复制
发表时间：
2021-11
期刊：
影响因子：
82.9
通讯作者：
Bar-Or A
中科院分区：
文献类型：
--
作者：
Apostolidis SA;Kakara M;Painter MM;Goel RR;Mathew D;Lenzi K;Rezk A;Patterson KR;Espinoza DA;Kadri JC;Markowitz DM;E Markowitz C;Mexhitaj I;Jacobs D;Babb A;Betts MR;Prak ETL;Weiskopf D;Grifoni A;Lundgreen KA;Gouma S;Sette A;Bates P;Hensley SE;Greenplate AR;Wherry EJ;Li R;Bar-Or A
SARS-CoV-2信使RNA疫苗接种健康个体可产生针对COVID-19的免疫保护。然而，关于SARS-CoV-2 mRNA疫苗在免疫抑制患者中诱导的应答知之甚少。我们纵向研究了BNT 162 b2或mRNA-1273 mRNA疫苗接种后，与健康对照组（n = 10）相比，多发性硬化症（MS）患者抗CD 20抗体单药治疗（n = 20）诱导抗原特异性抗体、B细胞和T细胞应答。在大多数患者中，抗CD 20单克隆抗体（aCD 20）治疗显著降低了棘突特异性和受体结合域（RBD）特异性抗体和记忆B细胞应答，随着末次aCD 20治疗持续时间的延长和B细胞重建程度的增加，这种效应有所改善。相比之下，所有接受aCD 20治疗的MS患者在接种疫苗后均产生抗原特异性CD 4和CD 8 T细胞应答。用aCD 20治疗使应答偏斜，损害循环滤泡辅助性T（TFH）细胞应答并增强CD 8 T细胞诱导，同时保留1型辅助性T（TH 1）细胞引发。用缺乏抗RBD IgG的aCD 20治疗的MS患者在循环TFH应答中具有最严重的缺陷和更稳健的CD 8 T细胞应答。这些数据定义了SARS-CoV-2疫苗诱导的aCD 20治疗患者免疫景观的性质，并提供了对人类协调mRNA疫苗诱导免疫应答的见解。我们的研究结果对免疫抑制患者（包括接受aCD 20治疗的患者）的临床决策和公共卫生政策具有重要意义。在BNT 162 b2或mRNA-1273 mRNA疫苗接种后，接受抗CD 20单药治疗的多发性硬化症患者与健康对照组相比，SARS-CoV-2特异性抗体和记忆B细胞显著减少，但CD 4+和CD 8 + T细胞强烈活化。
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20. SARS-CoV-2-specific antibodies and memory B cells are significantly reduced, but CD4+ and CD8+ T cells are robustly activated, in patients with multiple sclerosis on anti-CD20 monotherapy versus healthy controls after BNT162b2 or mRNA-1273 mRNA vaccination.
登录
查看更多内容
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
DOI：
10.1038/s41573-020-00092-2
发表时间：
2021-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Lee DSW;Rojas OL;Gommerman JL
通讯作者：
Gommerman JL
影响因子：
16.6
作者：
Belkina, Anna C.;Ciccolella, Christopher O.;Snyder-Cappione, Jennifer E.
通讯作者：
Snyder-Cappione, Jennifer E.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
24.8
作者：
Goel RR;Apostolidis SA;Painter MM;Mathew D;Pattekar A;Kuthuru O;Gouma S;Hicks P;Meng W;Rosenfeld AM;Dysinger S;Lundgreen KA;Kuri-Cervantes L;Adamski S;Hicks A;Korte S;Oldridge DA;Baxter AE;Giles JR;Weirick ME;McAllister CM;Dougherty J;Long S;D'Andrea K;Hamilton JT;Betts MR;Luning Prak ET;Bates P;Hensley SE;Greenplate AR;Wherry EJ
通讯作者：
Wherry EJ