NYU Multiple Sclerosis Comprehensive Care Center, Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA.
Laura and Isaac Perlmutter Cancer Center and Department of Pathology, NYU Grossman School of Medicine, New York, New York, USA.
Ann Clin Transl Neurol. 2024 Jul;11(7):1750-1764. doi: 10.1002/acn3.52081. Epub 2024 May 7.
(1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity.
Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses.
The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity.
Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.
(1)描绘 B 细胞耗竭性多发性硬化症（MS）患者在接种 COVID-19 mRNA 系列两剂初级疫苗和第三/加强针后，体液和细胞免疫应答的轨迹；(2)确定免疫反应的预测因素；(3)评估并发 COVID-19 感染对 SARS-CoV-2 特异性免疫的影响。
从纽约大学（NYU）和科罗拉多大学（安舒茨）MS 中心招募了 60 名接受奥瑞珠单抗治疗的 MS 患者。在接种疫苗前采集样本，然后在初级系列接种后 4、12、24 和 48 周，以及加强针接种后 4、12、24 和 48 周采集样本。使用多重珠粒免疫分析（MBI）和电化学发光（罗氏诊断 Elecsys®）评估结合 Spike 抗体反应，使用基于活病毒免疫荧光的微量中和测定法评估中和抗体反应。使用 IFNγ/IL-2 ELISpot（Invitrogen）评估 Spike 特异性细胞反应，在一部分患者中通过测序 T 细胞受体（适应性生物技术）中的互补决定区（CDR）-3 进行评估。使用线性混合效应模型比较不同时间点的抗体和细胞因子水平。多元分析确定了免疫反应的预测因素。
初级疫苗接种诱导结合和中和抗体水平增加 11-208 倍，IFNγ/IL-2 反应增加 3-4 倍，随后抗体但细胞因子反应略有下降。加强针诱导结合抗体增加 3-5 倍，IFNγ/IL-2 增加 4-5 倍，在长达 1 年内得到维持。感染对免疫有不同的影响。
在接种加强针时，B 细胞耗竭性 MS 患者的 COVID-19 疫苗接种的体液和细胞益处可持续长达 2 年。
