Knell Astrid I, Böhm Anna K, Jäger Michael, Kerschbaum Julia, Engl Sabine, Rudnicki Michael, Buchwinkler Lukas, Bellmann-Weiler Rosa, Posch Wilfried, Weiss Günter
Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria.
Microorganisms. 2023 Jul 5;11(7):1756. doi: 10.3390/microorganisms11071756.
Patients with chronic kidney disease (CKD) or immunosuppression are at increased risk of severe SARS-CoV-2 infection. The vaccination of CKD patients has resulted in lower antibody concentrations and possibly reduced protection. However, little information is available on how T-cell-mediated immune response is affected in those patients and how vaccine-induced immune responses can neutralise different SARS-CoV-2 variants. Herein, we studied virus-specific humoral and cellular immune responses after two doses of mRNA-1273 (Moderna) vaccine in 42 patients suffering from CKD, small vessel vasculitis (maintenance phase), or kidney transplant recipients (KT). Serum and PBMCs from baseline and at three months after vaccination were used to determine SARS-CoV-2 S1-specific antibodies, neutralisation titers against SARS-CoV-2 WT, B1.617.2 (delta), and BA.1 (omicron) variants as well as virus-specific T-cells via IFNγ ELISpot assays. We observed a significant increase in quantitative and neutralising antibody titers against SARS-CoV-2 and significantly increased T-cell responses to SARS-CoV-2 S1 antigen after vaccination only in the CKD patients. In patients with vasculitis, neither humoral nor cellular responses were detected. In KT recipients, antibodies and virus neutralisation against WT and delta, but not against omicron BA.1, was assured. Importantly, we found no specific SARS-CoV-2 T-cell response in vasculitis and KT subjects, although unspecific T-cell activation was evident in most patients even before vaccination. While pre-dialysis CKD patients appear to mount an effective immune response for in vitro neutralisation of SARS-CoV-2, KT and vasculitis patients under immunosuppressive therapy were insufficiently protected from SARS-CoV-2 two months after the second dose of an mRNA vaccine.
慢性肾脏病（CKD）患者或免疫抑制患者感染重症严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的风险增加。CKD患者接种疫苗后抗体浓度较低，可能导致保护作用降低。然而，关于这些患者的T细胞介导的免疫反应如何受到影响以及疫苗诱导的免疫反应如何中和不同的SARS-CoV-2变体，目前所知甚少。在此，我们研究了42例CKD、小血管血管炎（维持期）或肾移植受者（KT）在接种两剂mRNA-1273（Moderna）疫苗后的病毒特异性体液免疫和细胞免疫反应。采集基线期及接种疫苗后三个月的血清和外周血单个核细胞（PBMC），通过干扰素γ酶联免疫斑点试验（IFNγ ELISpot）检测针对SARS-CoV-2 S1的特异性抗体、针对SARS-CoV-2野生型（WT）、B1.617.2（德尔塔）和BA.1（奥密克戎）变体的中和滴度以及病毒特异性T细胞。我们观察到，仅在CKD患者中，接种疫苗后针对SARS-CoV-2的定量抗体滴度和中和抗体滴度显著增加，且针对SARS-CoV-2 S1抗原的T细胞反应也显著增强。在血管炎患者中，未检测到体液免疫和细胞免疫反应。在KT受者中，可检测到针对WT和德尔塔变体的抗体及病毒中和作用，但针对奥密克戎BA.1变体则未检测到。重要的是，我们发现血管炎患者和KT患者中未出现特异性的SARS-CoV-2 T细胞反应，尽管在大多数患者中，即使在接种疫苗前非特异性T细胞激活就已很明显。虽然透析前CKD患者似乎能产生有效的免疫反应以在体外中和SARS-CoV-2，但在接种第二剂mRNA疫苗两个月后，接受免疫抑制治疗的KT患者和血管炎患者对SARS-CoV-2的保护不足。
