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异基因造血干细胞移植后患者体液免疫对 COVID-19 疫苗接种的反应的影响因素和特征。

Risk factors and characteristics influencing humoral response to COVID-19 vaccination in patients after allogeneic stem cell transplantation.

机构信息

Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany.

Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.

出版信息

Front Immunol. 2023 May 3;14:1174289. doi: 10.3389/fimmu.2023.1174289. eCollection 2023.

Abstract

INTRODUCTION

Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARS-CoV-2 vaccination in a bicentric population of allogeneic transplanted patients.

METHODS

We retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination.

RESULTS

A total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts <200/μl, p< 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion.

DISCUSSION

We showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose.

摘要

简介

接种针对严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)的疫苗已获得批准并推荐用于免疫功能低下的患者,如异基因造血干细胞移植(allo-SCT)后的患者。由于感染是移植相关死亡的一个重要原因,我们分析了在两个异基因移植患者中心人群中,SARS-CoV-2 疫苗接种的出现。

方法

我们回顾性分析了两个德国移植中心的 allo-SCT 受者的数据,以了解他们在接受两剂和三剂 SARS-CoV-2 疫苗接种后的安全性和血清学反应。患者接受了 mRNA 疫苗或基于载体的疫苗。所有患者均在接种两剂和三剂后使用 IgG ELISA 法或 EIA 法检测针对 SARS-CoV2-刺突蛋白的抗体(抗-S-IgG)。

结果

共 243 例 allo-SCT 患者接受了 SARS-CoV-2 疫苗接种。中位年龄为 59 岁(范围 22-81)。85%的患者接受了两剂 mRNA 疫苗,10%的患者接受了基于载体的疫苗,5%的患者接受了混合疫苗接种。两剂疫苗接种耐受性良好,仅有 3%的患者发生移植物抗宿主病(GvHD)复发。总体而言,72%的患者在接受两剂疫苗接种后出现了体液反应。多变量分析显示, allo-SCT 时的年龄(p=0.0065)、持续的免疫抑制治疗(p=0.029)和免疫重建缺失(CD4-T 细胞计数<200/μl,p<0.001)与无反应相关。性别、预处理强度和 ATG 的使用对血清转化率没有影响。最后,在接受第二剂后未产生反应的 69 例患者中,有 44 例接受了加强剂,其中 57%(25/44)产生了血清转化。

讨论

我们在我们的两个异基因 SCT 患者队列中表明,特别是对于那些接受免疫重建且无免疫抑制剂的患者,可通过常规批准的方案获得体液反应。在最初接受两剂疫苗接种后无反应的 50%以上患者中,通过第三剂加强剂可实现血清转化率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd6/10190126/2e37c2a08410/fimmu-14-1174289-g001.jpg

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