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Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients
Science Immunology ( IF 17.6 ) Pub Date : 2021-06-15 , DOI: 10.1126/sciimmunol.abj1031
Hector Rincon-Arevalo 1, 2, 3, 4 , Mira Choi 1 , Ana-Luisa Stefanski 2, 3 , Fabian Halleck 1 , Ulrike Weber 1 , Franziska Szelinski 2, 3 , Bernd Jahrsdörfer 5 , Hubert Schrezenmeier 5 , Carolin Ludwig 5 , Arne Sattler 6 , Katja Kotsch 6 , Alexander Potekhin 7 , Yidan Chen 2, 3 , Gerd R Burmester 2 , Kai-Uwe Eckardt 1 , Gabriela Maria Guerra 3 , Pawel Durek 3 , Frederik Heinrich 3 , Marta Ferreira-Gomes 3 , Andreas Radbruch 3 , Klemens Budde 1 , Andreia C Lino 3 , Mir-Farzin Mashreghi 3, 8, 9 , Eva Schrezenmeier 1, 3, 10 , Thomas Dörner 2, 3
Affiliation  

Patients with kidney failure are at increased risk for SARS-CoV-2 infection making effective vaccinations a critical need. It is not known how well mRNA vaccines induce B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 35 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. The frequency and absolute number of antigen-specific circulating plasmablasts in the cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, these data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells. Thus, there is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.



中文翻译:

肾移植受者和透析患者对 SARS-CoV-2 BNT162b2 疫苗的体液免疫受损

肾功能衰竭患者感染 SARS-CoV-2 的风险增加,因此迫切需要有效的疫苗接种。与健康对照 (HC) 相比,目前尚不清楚 mRNA 疫苗在透析患者 (DP) 或肾移植受者 (KTR) 中诱导 B 细胞和浆细胞反应的效果如何。我们研究了 35 HC、44 DP 和 40 KTR 的体液和 B 细胞反应。与 HC 相比,在 KTR 和 DP 中发现了明显受损的抗 BNT162b2 反应。在 DP 中,反应被延迟(加强后 3-4 周)并随着抗 S1 IgG 和 IgA 阳性分别降低 70.5% 和 68.2%。相比之下,KTR 没有产生 IgG 反应,除了一名先前未发现感染并产生抗 S1 IgG 的患者。大多数抗原特异性 B 细胞 (RBD+) 在 HC 的浆母细胞或转换后记忆 B 细胞区室中被鉴定,而 RBD+ B 细胞在来自 DP 和 KTR 的转换前和初始 B 细胞中富集。队列中抗原特异性循环浆母细胞的频率和绝对数量与 Ig 反应相关,这是其他疫苗接种未报告的特征。总之,这些数据表明免疫抑制导致 mRNA 疫苗接种后保护性免疫受损,包括 Ig 诱导以及相应的浆母细胞和记忆 B 细胞的产生。因此,迫切需要改进肾移植后或慢性透析患者的疫苗接种方案。其他疫苗接种未报告的特征。总之,这些数据表明免疫抑制导致 mRNA 疫苗接种后保护性免疫受损,包括 Ig 诱导以及相应的浆母细胞和记忆 B 细胞的产生。因此,迫切需要改进肾移植后或慢性透析患者的疫苗接种方案。其他疫苗接种未报告的特征。总之,这些数据表明免疫抑制导致 mRNA 疫苗接种后保护性免疫受损,包括 Ig 诱导以及相应的浆母细胞和记忆 B 细胞的产生。因此,迫切需要改进肾移植后或慢性透析患者的疫苗接种方案。

更新日期:2021-06-15
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