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异基因造血细胞移植或嵌合抗原受体 T 细胞治疗后第一年的 SARS-CoV-2 疫苗接种:一项前瞻性、多中心、观察性研究。

SARS-CoV-2 Vaccination in the First Year After Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-Cell Therapy: A Prospective, Multicenter, Observational Study.

机构信息

Vaccine and Infectious Disease, Fred Hutchinson Cancer Center, and Department of Medicine, University of Washington, Seattle, Washington, USA.

Center for International Blood and Marrow Transplantation Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

出版信息

Clin Infect Dis. 2024 Aug 16;79(2):542-554. doi: 10.1093/cid/ciae291.

Abstract

BACKGROUND

The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy.

METHODS

We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to 5 time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T-cell receptors, in a subgroup.

RESULTS

We enrolled 466 allogeneic hematopoietic cell transplantation (HCT) (n = 231), autologous HCT (n = 170), and chimeric antigen receptor T-cell (CAR-T-cell) therapy (n = 65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months versus 4-12 months after cellular therapy. Anti-S IgG ≥2500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T-cell recipients, respectively. SARS-CoV-2-specific T-cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination and baseline B-cell count were key predictors of post-cellular therapy immunity.

CONCLUSIONS

These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation 3 to 4 months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T-cell therapy.

摘要

背景

细胞治疗后接种严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)疫苗的最佳时间尚不完全清楚。本研究的目的是确定细胞治疗后 4 个月内与 4-12 个月后开始接种 SARS-CoV-2 疫苗,其体液和细胞反应是否存在差异。

方法

我们在美国 30 家癌症中心进行了一项多中心、前瞻性、观察性研究。SARS-CoV-2 疫苗接种作为常规护理的一部分进行。我们在多达 5 个时间点采集接种前后的血液,并在所有参与者中检测 SARS-CoV-2 刺突(抗 S)IgG,以及武汉 D614G、Delta B.1.617.2 和奥密克戎 B.1.1.529 株的中和抗体,以及 SARS-CoV-2 特异性 T 细胞受体,在亚组中进行检测。

结果

我们在 2021 年 4 月至 2022 年 6 月期间纳入了 466 例异基因造血细胞移植(HCT)(n=231)、自体 HCT(n=170)和嵌合抗原受体 T 细胞(CAR-T 细胞)治疗(n=65)患者。细胞治疗后<4 个月和 4-12 个月开始接种疫苗的参与者之间,体液和细胞反应没有显著差异。抗-S IgG≥2500 U/mL 与高中和抗体滴度相关,在异基因 HCT、自体 HCT 和 CAR-T 细胞接受者中,最后时间点分别达到 70%、69%和 34%。SARS-CoV-2 特异性 T 细胞反应分别达到 57%、83%和 58%。细胞治疗前 SARS-CoV-2 感染或疫苗接种和基线 B 细胞计数是细胞治疗后免疫的关键预测因素。

结论

这些数据支持在异基因 HCT、自体 HCT 和 CAR-T 细胞治疗之前和之后 3-4 个月进行 mRNA SARS-CoV-2 疫苗接种。

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