Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients
Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients
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DOI：
10.1126/sciimmunol.abj1031
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发表时间：
2021-06-01
影响因子：
24.8
通讯作者：
Doerner, Thomas
中科院分区：
文献类型：
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作者：
Rincon-Arevalo, Hector;Choi, Mira;Doerner, Thomas
肾衰竭患者感染SARS-CoV-2的风险增加，因此迫切需要有效的疫苗接种。目前尚不清楚与健康对照组(HC)相比，在透析患者(DP)或肾移植受者(KTR)中，mRNA疫苗诱导B细胞和浆细胞反应的效果如何。我们研究了35只HC、44只DP和40只KTR的体液反应和B细胞反应。与HC相比，KTR和DP的抗BNT162b2反应明显减弱。DP组免疫应答延迟(强化后3~4周)，抗S1Ig G和Ig A阳性分别为70.5%和68.2%。相比之下，除了一名先前有未被识别的感染并发展为抗S1Ig G的患者外，Ktr没有发展出Ig G反应。在HC中，抗原特异性B细胞(RBD+)主要分布于浆母细胞或转换后记忆B细胞，而转换前和转换后的原始B细胞中，RBD+B细胞较丰富。队列中抗原特异性循环浆母细胞的频率和绝对数量与Ig应答相关，这一特征在其他疫苗中没有报道。综上所述，这些数据表明，免疫抑制导致了免疫保护性免疫受损，包括相应代成浆细胞和记忆B细胞的Ig诱导。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。
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 naive 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.