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基于载体的 SARS-CoV-2 疫苗接种与血液系统恶性肿瘤中 T 细胞反应的改善相关。

Vector-based SARS-CoV-2 vaccination is associated with improved T-cell responses in hematological neoplasia.

机构信息

Clinic III-Hematology, Oncology, and Palliative Care, Rostock University Medical Center, Rostock, Germany.

University Clinic and Outpatient Clinic for Internal Medicine IV, University Hospital Halle (Saale), Halle (Saale), Germany.

出版信息

Blood Adv. 2023 Jul 25;7(14):3403-3415. doi: 10.1182/bloodadvances.2022009054.

Abstract

In order to elucidate mechanisms for severe acute respiratory syndrome coronavirus 2 vaccination success in hematological neoplasia, we, herein, provide a comprehensive characterization of the spike-specific T-cell and serological immunity induced in 130 patients in comparison with 91 healthy controls. We studied 121 distinct T-cell subpopulations and the vaccination schemes as putative response predictors. In patients with lymphoid malignancies an insufficient immunoglobulin G (IgG) response was accompanied by a healthy CD4+ T-cell function. Compared with controls, a spike-specific CD4+ response was detectable in fewer patients with myeloid neoplasia whereas the seroconversion rate was normal. Vaccination-induced CD4+ responses were associated to CD8+ and IgG responses. Vector-based AZD1222 vaccine induced more frequently detectable specific CD4+ responses in study participants across all cohorts (96%; 27 of 28), whereas fully messenger RNA-based vaccination schemes resulted in measurable CD4+ cells in only 102 of 168 participants (61%; P < .0001). A similar benefit of vector-based vaccination was observed for the induction of spike-specific CD8+ T cells. Multivariable models confirmed vaccination schemes that incorporated at least 1 vector-based vaccination as key feature to mount both a spike-specific CD4+ response (odds ratio, 10.67) and CD8+ response (odds ratio, 6.56). Multivariable analyses identified a specific CD4+ response but not the vector-based immunization as beneficial for a strong, specific IgG titer. Our study reveals factors associated with a T-cell response in patients with hematological neoplasia and might pave the way toward tailored vaccination schemes for vaccinees with these diseases. The study was registered at the German Clinical Trials Register as #DRKS00027372.

摘要

为了阐明严重急性呼吸综合征冠状病毒 2 疫苗在血液恶性肿瘤中成功的机制,我们在此对 130 名患者与 91 名健康对照者进行了比较,全面描述了 Spike 特异性 T 细胞和血清免疫反应。我们研究了 121 种不同的 T 细胞亚群和接种方案,作为潜在的反应预测因子。在患有淋巴细胞恶性肿瘤的患者中,免疫球蛋白 G(IgG)反应不足伴随着健康的 CD4+T 细胞功能。与对照组相比,骨髓性肿瘤患者中检测到 Spike 特异性 CD4+反应的患者较少,而血清转化率正常。接种诱导的 CD4+反应与 CD8+和 IgG 反应相关。基于载体的 AZD1222 疫苗在所有队列的研究参与者中更频繁地诱导可检测的特异性 CD4+反应(96%;27/28),而完全基于信使 RNA 的疫苗方案仅在 168 名参与者中的 102 名(61%)中产生可测量的 CD4+细胞(P<.0001)。基于载体的疫苗接种在诱导 Spike 特异性 CD8+T 细胞方面也具有类似的益处。多变量模型证实,至少包含 1 种基于载体的疫苗接种的疫苗接种方案是产生 Spike 特异性 CD4+反应(优势比,10.67)和 CD8+反应(优势比,6.56)的关键特征。多变量分析确定了特异性 CD4+反应而不是基于载体的免疫接种对产生强特异性 IgG 滴度是有益的。本研究揭示了与血液恶性肿瘤患者的 T 细胞反应相关的因素,并可能为这些疾病的疫苗接种者制定定制疫苗接种方案铺平道路。该研究在德国临床试验注册中心注册,编号为 #DRKS00027372。

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