Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, Yamagata, Japan.
Front Immunol. 2022 Nov 30;13:1050211. doi: 10.3389/fimmu.2022.1050211. eCollection 2022.
We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.
我们评估了肾移植受者(KTR)在第二次接种疫苗后更长时间间隔接受第三剂严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)mRNA 疫苗的体液和细胞免疫反应和安全性。我们纳入了 54 名无 2019 年冠状病毒病(COVID-19)病史的肾移植受者,他们接受了第三剂疫苗。我们使用酶联免疫斑点(ELISpot)法在基线、第二次接种后和第三次接种后评估针对刺突蛋白的抗 SARS-CoV-2 刺突抗体和抗原特异性 T 细胞。我们还评估了与每剂疫苗相关的不良事件。第二次和第三次接种之间的间隔为 7±1 个月。第二次接种后抗 SARS-CoV-2 抗体阳性的 17 名(100%)KTR 中,和第二次接种后抗 SARS-CoV-2 抗体阴性的 37 名(73%)KTR 中有 27 名(73%)抗 SARS-CoV-2 抗体阳性(p=0.022)。抗 SARS-CoV-2 抗体滴度明显高于第二次接种后(p<0.001)。年龄≥60 岁和淋巴细胞计数<1150/mm3 被确认为多变量回归分析中第三次接种后抗 SARS-CoV-2 抗体阴性的危险因素。第二次接种后 ELISpot 细胞因子活性阳性的 29 名(90%)KTR 中有 26 名(90%)和第二次接种后 ELISpot 细胞因子活性阴性的 24 名(50%)中的 12 名(50%)在第三次接种后细胞因子活性阳性。第三次接种后细胞因子活性的变化率明显高于第二次接种后(p<0.001)。多变量回归分析中仅淋巴细胞计数<1150/mm3 被确认为 ELISpot 细胞因子活性阴性的危险因素。每个疫苗剂量的全身性不良事件发生率均无差异。大于中度的分类。没有患者出现急性排斥反应的临床症状。在 KTR 中,更长时间间隔的第三剂 SARS-CoV-2 mRNA 疫苗接种可改善对 SARS-CoV-2 mRNA 疫苗的体液和细胞免疫反应,且无严重不良事件。