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新型冠状病毒肺炎信使核糖核酸疫苗接种后异基因造血干细胞受体的抗体、细胞介导反应及感染易感性

Antibody, cell-mediated response and infection susceptibility in allogeneic hematopoietic stem cell recipients after COVID-19 mRNA vaccination.

作者信息

Pizzano Umberto, Facchin Gabriele, Marcon Chiara, Fabris Martina, Battista Marta Lisa, Cerno Michela, Geromin Antonella, Pucillo Martina, Petruzzellis Giuseppe, Vianello Giampaolo, Battaglia Giulia, Peressutti Roberto, Grillone Lucrezia, Tascini Carlo, Curcio Francesco, Fanin Renato, Patriarca Francesca

机构信息

Division of Hematology and Stem Cell Transplantation, University Hospital ASUFC, Udine, Italy.

Department of Medical Area (DAME), University of Udine, Udine, Italy.

出版信息

Transpl Infect Dis. 2023 Apr;25(2):e14003. doi: 10.1111/tid.14003. Epub 2023 Feb 7.

Abstract

BACKGROUND

Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion.

METHODS

We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein.

RESULTS

Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk.

CONCLUSIONS

Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies.

摘要

背景

接受异基因干细胞移植(allo-SCT)的患者由于与移植物抗宿主病(GvHD)预防和治疗相关的免疫抑制状态,对疫苗的反应降低。在我们的研究中,我们根据患者和移植特征比较了抗SARS-CoV-2 mRNA疫苗的体液反应以及感染的发生情况;我们还评估了血清未转化患者的细胞反应。

方法

我们检测了第二剂和第三剂疫苗接种后的抗体滴度。通过免疫酶测定法检测抗体。在一个血清未转化的患者亚组中,我们通过评估暴露于病毒刺突蛋白的T淋巴细胞释放的干扰素-γ来检测细胞介导的反应。

结果

第二剂疫苗接种后30天的血清转化率从66%升至90天的81%;第三剂疫苗接种后150天为97%。我们发现第二剂疫苗接种后的血清转化与两个变量之间存在显著关联:allo-SCT与疫苗接种之间的间隔较短;正在进行免疫抑制。19例第二剂疫苗接种后无抗体的患者中有12例(63%)未显示细胞反应。19%的患者在第三剂疫苗接种后发生了SARS-CoV-2感染,所有病例的结果均良好。allo-SCT后12个月内的患者感染风险显著更高。

结论

我们的研究表明,allo-SCT与第一剂疫苗接种之间的间隔短于12个月和/或正在进行免疫抑制与两剂疫苗接种后的体液和细胞反应缺陷有关。第三剂疫苗在大多数患者中诱导了增强且持续的体液反应。然而,allo-SCT后1年内的患者感染风险仍然较高,可能是抗SARS-CoV-2单克隆抗体预防的候选对象。

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