There is evidence of reduced SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. We hypothesized that tumor and treatment-related immunosuppression can be depicted in peripheral blood, and that immune profiling prior to vaccination can help predict immunogenicity. We performed a comprehensive immunological characterization of 83 hematological patients before vaccination and measured IgM, IgG, and IgA antibody response to four viral antigens at day +7 after second-dose COVID-19 vaccination using multidimensional and computational flow cytometry. Health care practitioners of similar age were the control group (n = 102). Forty-four out of 59 immune cell types were significantly altered in patients; those with monoclonal gammopathies showed greater immunosuppression than patients with B-cell disorders and Hodgkin lymphoma. Immune dysregulation emerged before treatment, peaked while on-therapy, and did not return to normalcy after stopping treatment. We identified an immunotype that was significantly associated with poor antibody response and uncovered that the frequency of neutrophils, classical monocytes, CD4, and CD8 effector memory CD127low T cells, as well as naive CD21+ and IgM+D+ memory B cells, were independently associated with immunogenicity. Thus, we provide novel immune biomarkers to predict COVID-19 vaccine effectiveness in hematological patients, which are complementary to treatment-related factors and may help tailoring possible vaccine boosters.

有证据表明 SARS-CoV-2 疫苗对血液恶性肿瘤患者的有效性降低。我们假设肿瘤和治疗相关的免疫抑制可以在外周血中描述，并且疫苗接种前的免疫分析可以帮助预测免疫原性。我们在接种疫苗前对 83 名血液病患者进行了全面的免疫学表征，并使用多维和计算流式细胞术在第二剂 COVID-19 疫苗接种后第 +7 天测量了对四种病毒抗原的 IgM、IgG 和 IgA 抗体反应。年龄相仿的医疗保健从业人员为对照组（n  = 102）。患者体内 59 种免疫细胞类型中有 44 种发生了显着改变；患有单克隆丙种球蛋白病的患者比患有 B 细胞疾病和霍奇金淋巴瘤的患者表现出更强的免疫抑制。免疫失调在治疗前出现，在治疗期间达到顶峰，并且在停止治疗后没有恢复正常。我们确定了一种与抗体反应不良显着相关的免疫类型，并发现中性粒细胞、经典单核细胞、CD4 和 CD8 效应记忆 CD127low T 细胞以及初始 CD21+ 和 IgM+D+ 记忆 B 细胞的频率与抗体反应独立相关。免疫原性。因此，我们提供了新型免疫生物标志物来预测血液病患者中的 COVID-19 疫苗有效性，这些标志物与治疗相关因素相补充，并可能有助于定制可能的疫苗加强剂。