All patients were serologically proven SARS-CoV-2 negative prior to vaccination

All patients were serologically proven SARS-CoV-2 negative prior to vaccination. SARS-CoV-2 spike protein-specific interferon- release assay. Results The seroconversion rate was 47.2%, 100%, 69.4% and 100% one month Ro 08-2750 after the 1st dose, one and six months after the 2nd dose and four months after the heterologous 3rd dose. The median Ro 08-2750 (Q1, Q3) anti-SARS-CoV-2 spike IgG concentrations at the same time were 28.7 (13.2, 69.4) BAU/ml, 1130.0 (594.5, 1735.0) BAU/ml, 89.7 (26.4, 203.8) BAU/ml, and 2080.0 (1062.5, 2080.0) BAU/ml. The percentage of patients with neutralizing antibodies was 58.3% after the 2nd dose and improved to 100% after the 3rd dose (value 0.05 was deemed to indicate statistical significance. All statistical Ro 08-2750 analyses were performed with IBM SPSS Statistics 26 (IBM, Armonk (NY), USA). Results Baseline characteristics of the 36 hemodialysis patients (mean (SD) age 66.9 (15.9) years, 33.3% females) with complete triple-vaccination and follow-up over the 13 months are given in Table?1 . Table?1 Baseline patients characteristics. = 0.089), anti-spike IgG concentrations differed significantly comparing the four time points ( 0.001 for all). Open in a separate window Figure?2 Anti-SARS-CoV-2-spike protein IgG concentration after heterologous triple vaccination with the mRNA-BNT162b2 and vector Ad26COVS1 vaccine in hemodialysis MAPKK1 patients. Violin plots (combining box and kernel density plots) including individual data points are displayed. The red line indicates the median, the red dotted lines the first and third quartile. The threshold for seropositivity is 33.8 BAU/ml. **** 0.0001; *** 0.001; ns, not significant (= 0.089). To further analyze the neutralizing capacity, we additionally assessed neutralizing antibodies six months after complete mRNA vaccination and again four months Ro 08-2750 after the heterologous vaccine Ad26COVS1. The median (Q1, Q3) percent virus neutralization was 40.4% (32.6, 47.1) at month 7 and significantly increased to 97.1% (89.8, 97.6) at month 13 ( 0.001); the percentage of patients above the 30% threshold for neutralizing antibody positivity was 58.3% and 100% ( 0.001), respectively. With a specimen ratio cut-off value of 0.8, all patients had negative anti-SARS-CoV-2 nucleocapsid antibodies with a mean (SD) specimen ratio of 0.12 (0.04) at month 7 and 0.20 (0.14) at month 13, indicating a very low probability of an undetected asymptomatic natural infection between 2nd and 3rd and after the 3rd vaccination. A positive SARS-CoV-2 specific T-cell response assessed by IGRA was found in 50% of patients four months after the 3rd vaccination (month 13), with a median (Q1, Q3) of 0.152 IU/ml (0.065, 1.373). A positive cellular response at month 13 was associated with higher anti-SARS-CoV-2 spike IgG concentrations at all four time points (month 1, month 2, month 7, month 13), although the difference between patients with and without positive T-cellular response reached statistical significance at month 1 only (month 1: 55.4 [21.7, 99.6] vs 15.5 [11.7, 38.6] BAU/ml, = 0.004; month 2: 1440 [871.3, 2080] vs 995 [305, 1380] BAU/ml, = 0.064; month 7: 128.5 [36.4, 469.8] vs 53 [20.8, 125.8] BAU/ml, = 0.051; month 13: 2080 [1787.5, 2080] vs 1605 [781.8, 2080] BAU/ml, = 0.126). Baseline characteristics from patients with a positive cellular response did not significantly differ from patients without cellular response, except that positive patients were more often treated with calcitriol (89% vs 56%, = 0.026). Overall, the heterologous 3rd dose was well tolerated. Mild pain at the injection site was the only patient self-reported local reaction in a minority of patients. One patient with IgA nephropathy as primary renal disease reported about a vaccine-associated IgA nephropathy flare with gross hematuria for several days after the 3rd dose, but without other systemic reactions. During the complete follow-up no patient acquired symptomatic and PCR-confirmed SARS-CoV-2 infection. Discussion In our study we found a significantly improved immunogenicity including the neutralizing antibody response up to four months after a third heterologous SARS-CoV-2 vaccine dose in hemodialysis patients. Albeit a 2-months shorter follow-up, the SC rate four months after the 3rd heterologous dose was significantly higher than six months after two homologous doses, with even higher absolute antibody concentrations compared to the evaluation one month after the homologous doses. This promising humoral response might indicate the possibility to extend the interval for future booster vaccinations in our extremely vulnerable hemodialysis patients. After a high seroconversion rate following the two mRNA-vaccine doses, we observed a significant decline of anti-SARS-CoV-2 spike IgG concentrations over six months. This finding is in line with other reports (16). The early and fast waning of the humoral response prompted a third booster vaccination. Available data are very.