From the Department of Urology, , Women's Medical University Hospital, Tokyo, Japan.
From the Department of Transplant Medicine, Women's Medical University Hospital, Tokyo, Japan.
Exp Clin Transplant. 2022 May;20(5):463-471. doi: 10.6002/ect.2022.0020. Epub 2022 May 23.
Although the effectiveness of vaccines in protecting the host from infection has been proven, few surveys have been conducted on changes in antibody levels after vaccination of kidney transplant recipients in Japan.
We analyzed serological responses in kidney transplant recipients after BNT162B2 COVID-19 mRNA vaccine with the use of a reagent capable of simultaneously specifying the antibody response to 5 proteins: a full-spike protein (extracellular domain), 3 individual domains of the spike protein (S1, S2, and receptor-binding domain), and nucleocapsid. The analysis involved 111 patients who had follow-up over 1 month after having received the second of 2 coronavirus vaccines after kidney transplant.
Antibodies were detected in 46 of 111 patients (41%). The antibody-positive rate in the kidney transplant group tended to be lower than that in the healthy control group, which showed an antibody- positive rate of 100%. When the antibody-positive rate was analyzed by the type of immunosuppressor used, the rate was 36% (37/100) for patients who used tacrolimus at the time of vaccination and 90% (9/10) for patients who used cyclosporine. Patients administered CD20 antibody (rituximab) before and/or after transplant showed a lower production of antibodies, which was supported by a smaller number of CD19- and CD20-positive cells in the peripheral blood as well as a shorter period between rituximab administration and vaccination. The percentage of responding viral fragments varied greatly among individual patients and showed no uniformity in the kidney transplant group, whereas the mean fluorescence intensity of individual fragments showed a certain tendency in the control group.
The appropriate timing of vaccination should be considered in transplant recipients who use tacrolimus-mycophenolate mofetil combination and rituximab as these drugs are deeply related to a lower antibody response to SARS-CoV-2 BNT162b2 vaccination.
尽管疫苗在保护宿主免受感染方面的有效性已得到证实，但针对日本肾移植受者接种疫苗后抗体水平变化的调查较少。
我们使用一种能够同时特异性检测 5 种蛋白抗体反应的试剂，对 BNT162B2 COVID-19 mRNA 疫苗接种后的肾移植受者进行血清学反应分析：一种全长刺突蛋白（细胞外域）、3 种刺突蛋白的单独结构域（S1、S2 和受体结合域）和核衣壳。该分析涉及 111 例在肾移植后接受 2 剂冠状病毒疫苗后随访超过 1 个月的患者。
在 111 例患者中有 46 例（41%）检测到抗体。肾移植组的抗体阳性率倾向于低于健康对照组，后者的抗体阳性率为 100%。当按使用的免疫抑制剂类型分析抗体阳性率时，接种疫苗时使用他克莫司的患者为 36%（37/100），而使用环孢素的患者为 90%（9/10）。在移植前和/或移植后接受 CD20 抗体（利妥昔单抗）治疗的患者产生的抗体较少，这得到了外周血中 CD19 和 CD20 阳性细胞数量较少以及利妥昔单抗给药与疫苗接种之间时间较短的支持。个体患者之间反应性病毒片段的百分比差异很大，肾移植组没有统一的趋势，而对照组中各片段的平均荧光强度则显示出一定的趋势。
使用他克莫司-霉酚酸酯联合利妥昔单抗的移植受者应考虑适当的疫苗接种时机，因为这些药物与 SARS-CoV-2 BNT162b2 疫苗接种后抗体反应较低密切相关。
