Improved cellular and humoral immunity upon a second BNT162b2 and mRNA-1273 boost in prime-boost vaccination no/low responders with end-stage renal disease
Authors: Ulrik Stervbo, Arturo Blazquez-Navarro, Elena Vidal Blanco, Lema Safi, Toni L. Meister, Krystallenia Paniskaki, Mara Stockhausen, Corinna Marheinecke, Gert Zimmer, Jacqueline Wellenkötter, Tina Giglio, Prerna Arora, Stefan Pöhlmann, Markus Hoffmann, Felix S. Seibert, Stephanie Pfaender, Toralf Roch, Timm H. Westhoff, Okan Cinkilic, Nina Babel
Journal: Kidney International (2021)

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.1Stumpf J. Siepmann T. Lindner T. et al.Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: a prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.Lancet Reg Health Eur. 2021; 9: 100178Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar, 2Thieme C, Blazquez-Navarro A, Safi L, et al. Impaired humoral but substantial cellular immune response to variants of concern B1.1.7 and B.1.351 in hemodialysis patients after vaccination with BNT162b2. J Am Soc Nephrol, in press.Google Scholar, 3Blazquez-Navarro A. Safi L. Meister T.L. et al.Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2-vaccinated dialysis patients.Kidney Int. 2021; 100: 698-700Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar 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. Enzyme-linked immunosorbent assay, pseudovirus neutralization assay, and flow cytometry were applied to assess humoral and cellular immunity against the spike (S) protein of SARS-CoV-2 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 CD4+ 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 CD4+ T cells were comparable between both cohorts (Figure 1i and j), WT neutralizing capacity and S-WT– and Delta-reactive CD8+ T cells and S-reactive Tfh cells were significantly higher in NR/LR after the second booster (third dose) compared with HR requiring only 1 booster (2 doses; Figure 1g, h, n, and o). Our data demonstrate that patients with ESRD can benefit from a second vaccination boost by improving their cellular and humoral immunity not only to the vaccination-specific strain but also against the globally expanding Delta-VOC. Download .pdf (.96 MB) Help with pdf files Supplementary File (PDF) Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2-vaccinated dialysis patientsKidney InternationalVol. 100Issue 3PreviewPatients undergoing maintenance dialysis (DP) have a high risk of fatal coronavirus disease 2019 (COVID-19).1 Recent epidemiological data raise apprehension with respect to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) for DP.2,3 Therefore, ensuring cellular and humoral immunity directed to SARS-CoV-2 including VOC isolates is essential for this population. There are no data on vaccine-induced nor on natural SARS-CoV-2 infection–induced long-term immunity and its responsiveness to VOC isolates in DP. Full-Text PDF