Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine-induced antibody and T cell immunity and function.
Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine-induced antibody and T cell immunity and function.
复制标题
DOI：
10.1172/jci.insight.156978
复制
发表时间：
2022-02-22
期刊：
影响因子：
8
通讯作者：
Bove R
中科院分区：
文献类型：
--
作者：
Sabatino JJ Jr;Mittl K;Rowles WM;McPolin K;Rajan JV;Laurie MT;Zamecnik CR;Dandekar R;Alvarenga BD;Loudermilk RP;Gerungan C;Spencer CM;Sagan SA;Augusto DG;Alexander JR;DeRisi JL;Hollenbach JA;Wilson MR;Zamvil SS;Bove R
疫苗诱导的适应性免疫是控制SARS-CoV-2感染的先决条件。多发性硬化症（MS）疾病修饰疗法（dmt）不同地针对体液和细胞免疫。需要对MS dmt对SARS-CoV-2疫苗特异性免疫的影响进行全面比较，包括定量和功能性B细胞和T细胞反应。在80名研究参与者中，在接种SARS-CoV-2疫苗之前和之后测量了尖峰特异性Ab和T细胞反应，包括健康对照组和6组DMT患者：未经治疗和接受醋酸格拉替拉默（GA）、富马酸二甲酯（DMF）、那他珠单抗（NTZ）、鞘氨醇-1-磷酸（S1P）受体调节剂和抗cd20单抗治疗。通过Luminex试验、VirScan和假病毒中和来评估抗spike- ab反应。针刺特异性CD4+和CD8+ T细胞反应通过激活诱导的标志物和细胞因子表达和四聚体来表征。抗刺突IgG水平在健康对照组和未经治疗的MS患者以及接受GA、DMF或NTZ治疗的患者之间相似，但在抗cd20 mAb和s1p治疗的患者中有所降低。抗cd20单抗治疗患者的抗尖峰血清阳性与CD19+ B细胞水平相关，与累积治疗时间呈负相关。在抗cd20 mAb和s1p治疗的患者中，刺突表位反应性和假病毒中和性降低。在所有组中，尖峰特异性CD4+和CD8+ T细胞的反应性都保持强劲，但s1p治疗的患者除外，后者疫苗后CD4+ T细胞反应减弱。这些发现来自于暴露于广泛MS免疫疗法的大型MS患者队列，对治疗特异性COVID-19临床指南具有重要意义。NIH资助项目1K08NS107619、K08NS096117、R01AI159260、R01NS092835、R01AI131624和R21NS108159；NMSS授予TA-1903-33713和RG1701-26628；Westridge基金会;陈·扎克伯格Biohub；Maisin基础。
Vaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses. Spike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti–spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer. Anti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb– and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb–treated patients was correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb– and S1P-treated patients. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4+ T cell responses were attenuated. These findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines. NIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.
登录
查看更多内容
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
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：
10.1073/pnas.1810470115
发表时间：
2018-09-25
影响因子：
11.1
作者：
Häusler D;Häusser-Kinzel S;Feldmann L;Torke S;Lepennetier G;Bernard CCA;Zamvil SS;Brück W;Lehmann-Horn K;Weber MS
通讯作者：
Weber MS
影响因子：
20.3
作者：
Han, SH;Zhang, XJ;Zheng, B
通讯作者：
Zheng, B