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 (T_FH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T_H1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T_FH 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.

健康个体接种 SARS-CoV-2 信使 RNA 疫苗可产生针对 COVID-19 的免疫保护。然而，人们对 SARS-CoV-2 mRNA 疫苗在免疫抑制患者中诱导的反应知之甚少。我们纵向研究了接受抗 CD20 抗体单一疗法 ( n  = 20) 的多发性硬化症 (MS) 患者与健康对照 ( n  = 10) 在 BNT162b2 或 mRNA-1273 治疗后诱导抗原特异性抗体、B 细胞和 T 细胞反应的情况mRNA疫苗接种。在大多数患者中，抗 CD20 单克隆抗体 (aCD20) 治疗显着降低了尖峰特异性和受体结合域 (RBD) 特异性抗体以及记忆 B 细胞反应，这种效果随着上次 aCD20 治疗持续时间的延长和 B 细胞范围的延长而改善重构。相比之下，所有接受 aCD20 治疗的多发性硬化症患者在接种疫苗后都会产生抗原特异性 CD4 和 CD8 T 细胞反应。使用 aCD20 治疗反应会出现偏差，损害循环滤泡辅助 T (T _FH ) 细胞反应并增强 CD8 T 细胞诱导，同时保留 1 型辅助 T (T _H 1) 细胞启动。_{使用缺乏抗 RBD IgG 的 aCD20 治疗的 MS 患者在循环 T FH}反应和更强大的 CD8 T 细胞反应方面存在最严重的缺陷。这些数据定义了 aCD20 治疗患者中 SARS-CoV-2 疫苗诱导的免疫景观的性质，并提供了对人类协调 mRNA 疫苗诱导的免疫反应的见解。我们的研究结果对免疫抑制患者（包括接受 aCD20 治疗的患者）的临床决策和公共卫生政策具有影响。