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日本肾移植受者接种两剂SARS-CoV-2 mRNA疫苗后外周血的免疫印记

Immunological imprint on peripheral blood in kidney transplant recipients after two doses of SARS-CoV-2 mRNA vaccination in Japan.

作者信息

Takiguchi Shinya, Tomita Yusuke, Uehara Saeko, Tateishi Koichiro, Yamamoto Norio, Nakamura Michio

机构信息

Department of Transplant Surgery, Tokai University School of Medicine, Kanagawa, Japan.

Department of Virology, Division of Host Defense Mechanism, School of Medicine, Tokai University, Kanagawa, Japan.

出版信息

Front Med (Lausanne). 2022 Sep 28;9:999374. doi: 10.3389/fmed.2022.999374. eCollection 2022.

Abstract

The immunological imprint after two doses of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) mRNA vaccination for patients after kidney transplantation (KTx) remain unclear. This study included KTx recipients and volunteer healthy controls (HCs) who received two doses of SARS-CoV-2 mRNA vaccine (Pfizer BioNTech) from January 2021 to December 2021. We analyzed safety within 21 days after each vaccination dose and compared the immune response in peripheral blood mononuclear cells (PBMCs) between the two groups. No graft rejection was observed throughout this study. Adverse events were generally observed within 5 days. The KTx group exhibited a significantly lower degree of symptoms between doses 1 and 2 ( < 0.001). Increases in activated subsets of T and B cells expressing human leukocyte antigen (HLA)-DR and/or CD38 were observed in the HC group after dose 2 (both < 0.001), with the greatest increases in HLA-DRCD8 T cells and CD38CD19 B cells ( = 0.042 and = 0.031, respectively). In addition, PD1CD8 T cells-but not PD1CD4 T cells-increased significantly in the HC group ( = 0.027). In the KTx group, however, activated HLA-DR, CD38, and PD1 cells remained at baseline levels. Immunoglobulin (Ig)G against SARS-CoV-2 was detected in only four KTx recipients (13.3%) after dose 2 ( < 0.001). Multivariate logistic regression analyses revealed that ΔHLA-DRCD8 T cells and ΔCD38CD19 B cells were significantly associated with IgG formation (both = 0.02). SARS-CoV-2 mRNA vaccine generates impaired cellular and humoral immunity for KTx recipients. Results indicate the need for modified vaccination strategies in immunocompromised KTx recipients.

摘要

肾移植(KTx)患者接种两剂严重急性呼吸综合征冠状病毒2(SARS-CoV-2)mRNA疫苗后的免疫印记仍不清楚。本研究纳入了2021年1月至2021年12月期间接受两剂SARS-CoV-2 mRNA疫苗(辉瑞BioNTech)的KTx受者和健康志愿者对照(HCs)。我们分析了每次接种疫苗后21天内的安全性,并比较了两组外周血单个核细胞(PBMCs)中的免疫反应。在整个研究过程中未观察到移植排斥反应。不良事件一般在5天内出现。KTx组在第1剂和第2剂之间出现症状的程度显著较低(<0.001)。第2剂接种后,HC组中表达人类白细胞抗原(HLA)-DR和/或CD38的T和B细胞活化亚群增加(均<0.001),其中HLA-DR⁺CD8⁺ T细胞和CD38⁺CD19⁺ B细胞增加最为明显(分别为=0.042和=0.031)。此外,HC组中PD-1⁺CD8⁺ T细胞显著增加,但PD-1⁺CD4⁺ T细胞未增加(=0.027)。然而,在KTx组中,活化的HLA-DR、CD38和PD-1细胞仍保持在基线水平。第2剂接种后,仅在4名KTx受者(13.3%)中检测到针对SARS-CoV-2的免疫球蛋白(Ig)G(<0.001)。多因素逻辑回归分析显示,ΔHLA-DR⁺CD8⁺ T细胞和ΔCD38⁺CD19⁺ B细胞与IgG形成显著相关(均=0.02)。SARS-CoV-2 mRNA疫苗对KTx受者的细胞免疫和体液免疫产生损害。结果表明,免疫功能低下的KTx受者需要改进疫苗接种策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73d6/9553995/cb858349bba6/fmed-09-999374-g001.jpg

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