Imhof Céline, Messchendorp A Lianne, van der Heiden Marieke, Baan Carla C, van der Molen Renate G, Remmerswaal Ester B M, de Vries Rory D, Diavatopoulos Dimitri A, Boerma Annemarie, Bakker Femke J, Oosterhout Emily, Bemelman Frederike J, Hilbrands Luuk B, Reinders Marlies E J, Gansevoort Ron T, Sanders Jan-Stephan, van Baarle Debbie
Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, Groningen, The Netherlands.
Transplant Direct. 2022 Oct 18;8(11):e1387. doi: 10.1097/TXD.0000000000001387. eCollection 2022 Nov.
Studies have shown that coronavirus disease 2019 (COVID-19) vaccination is associated with a lower humoral response in vulnerable kidney patients. Here, we investigated the T-cell response following COVID-19 vaccination in kidney patients compared with controls.
Patients with chronic kidney disease (CKD) stage G4/5 [estimated glomerular filtration rate <30 mL/min/1.73 m2], on dialysis, or living with a kidney transplant and controls received 2 doses of the mRNA-1273 COVID-19 vaccine. Peripheral blood mononuclear cells were isolated at baseline and 28 d after the second vaccination. In 398 participants (50% of entire cohort; controls n = 95, CKD G4/5 n = 81, dialysis n = 78, kidney transplant recipients [KTRs] n = 144)' SARS-CoV-2-specific T cells were measured using an IFN-γ enzyme-linked immune absorbent spot assay.
A significantly lower SARS-CoV-2-specific T-cell response was observed after vaccination of patients on dialysis (54.5%) and KTRs (42.6%) in contrast to CDK G4/5 (70%) compared with controls (76%). The use of calcineurin inhibitors was associated with a low T-cell response in KTRs. In a subset of 20 KTRs, we observed waning of the cellular response 6 mo after the second vaccination, which was boosted to some extent after a third vaccination, although T-cell levels remained low.
Our data suggest that vaccination is less effective in these patient groups, with humoral nonresponders also failing to mount an adequate cellular response, even after the third vaccination. Given the important role of T cells in protection against disease and cross-reactivity to SARS-CoV-2 variants, alternative vaccination strategies are urgently needed in these high-risk patient groups.
研究表明，2019冠状病毒病（COVID-19）疫苗接种在脆弱的肾脏患者中与较低的体液反应相关。在此，我们调查了肾脏患者与对照组相比在COVID-19疫苗接种后的T细胞反应。
慢性肾脏病（CKD）G4/5期[估计肾小球滤过率<30 mL/min/1.73 m²]、接受透析或肾移植的患者以及对照组接受2剂mRNA-1273 COVID-19疫苗。在基线和第二次接种后28天分离外周血单个核细胞。在398名参与者（占整个队列的50%；对照组n = 95，CKD G4/5期n = 81，透析组n = 78，肾移植受者[KTRs]n = 144）中，使用γ干扰素酶联免疫吸附斑点试验测量SARS-CoV-2特异性T细胞。
与对照组（76%）相比，透析患者（54.5%）和KTRs（42.6%）接种疫苗后观察到的SARS-CoV-2特异性T细胞反应明显低于CKD G4/5期患者（70%）。使用钙调神经磷酸酶抑制剂与KTRs中低T细胞反应相关。在20名KTRs的亚组中，我们观察到第二次接种后6个月细胞反应减弱，第三次接种后在一定程度上有所增强，尽管T细胞水平仍然较低。
我们的数据表明，疫苗接种在这些患者群体中效果较差，体液无反应者即使在第三次接种后也未能产生足够的细胞反应。鉴于T细胞在预防疾病和对SARS-CoV-2变体的交叉反应中的重要作用，这些高危患者群体迫切需要替代疫苗接种策略。
