LAUSR

To the editor: Patients with end-stage renal disease (ESRD) develop inefficient immune responses upon vaccination and have a high risk of developing severe coronavirus disease 2019 (COVID-19). The globally expanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC), B.1.6.17.2/Delta, evades immune responses and might constitute a particular threat to these patients. Herein, we evaluated the efficacy of a third dose (second boost) by BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) mRNA vaccines (Supplementary Table S1 and Supplementary Figure S1) in ESRD patients with no response/ low response (NR/LR) after prime-boost BNT162b2 vaccination and compared with ESRD with high response (HR) following the regular prime-boost vaccination. Enzymelinked immunosorbent assay, pseudovirus neutralization assay, and flow cytometry were applied to assess humoral and cellular immunity against the spike (S) protein of SARS-CoV2 wild type (WT-S) and the Delta-VOC (Delta-VOC-S) before and 3 to 5 weeks following the last booster vaccination. In NR/LR, 20 of 23 patients developed high-binding WT-S antibody titers (Figure 1a and Supplementary Figure S2A), with neutralizing capacity in 19 of 22 patients. The third vaccination led to an increase in WT-S protein-reactive CD4þ T cells (Figure 1b) without differences between the applied vaccines (Supplementary Figure S2B and C). The higher frequency of S-reactive T follicular helper (Tfh) cells was the only difference observed in mRNA-1273–boosted patients (Supplementary Figure S2D). Cellular immunity against WT-S and Delta-VOC-S was comparable irrespectively of helper or cytotoxic T cells or vaccine type (Figure 1e and f and Supplementary Figure S2E and F). In contrast, only 8 had neutralizing antibodies against Delta-VOC-S (Figure 1g). A clear association between cellular and humoral immunity was observed for each patient (Figure 1h). More important, when comparing the data obtained from NR/LR following the third dose with ESRD HR after the second dose, overall, superior results in cellular immunity and WT neutralizing capacity were observed. Although S-binding antibody titers and S-reactive CD4þ T cells were comparable between both cohorts (Figure 1i and j), WT neutralizing capacity and S-WT– and Delta-reactive CD8þ T cells and S-reactive Tfh cells were significantly higher in NR/LR after the second booster (third dose)