A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile

Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses and enhances comparatively more Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.

Short-term antibody response and tolerability of one dose of BNT162b2 vaccine in patients receiving hemodialysis

BackgroundPatients receiving in-center hemodialysis (HD) are at high risk of exposure to SARS-CoV-2 with high mortality, and response to vaccination is uncertain. MethodsWe obtained serial plasma from 58 HD patients and 32 health-care workers (HCW) before and after vaccination with one dose of the BNT162b2 mRNA vaccine; as well as convalescent plasma from 11 HD patients who survived COVID-19. Anti-RBD (region binding domain of the SARS-CoV-2 Spike protein) IgG and IgM levels were measured by ELISA. Groups were stratified by evidence of prior SARS-CoV-2 infection. ResultsIn HD patients without prior SARS-CoV-2, antiRBD levels were significantly lower at 4 and 8 weeks after vaccination, compared to in HCWs after 3 weeks (p<0.001), and to convalescent plasma (p=0.002). Anti-RBD IgG was non-detectable in 29/46 (63%) of HD, compared to 1/16 (6%) of HCWs (p<0.0001). No patient with non-detectable levels at 4 weeks developed antiRBD by 8 weeks. In HD patients with prior SARS-CoV-2, mean 8-week anti-RBD IgG levels were similar to controls at 3 weeks (p=0.16), and to convalescent plasma (p=0.45). No patients reported symptoms 7 days after vaccination on a standardized questionnaire. InterpretationWhile the BNT162b2 vaccine was well-tolerated in hemodialysis patients, a single dose failed to elicit a humoral immune response in the majority of SARS-CoV-2 naive patients even after prolonged observation. In those with prior SARS-CoV-2 infection, the humoral response after vaccination was delayed. Whether HD patients develop T-cell responses requires further study. Until then, we advise the second dose be administered to all HD patients at the recommended 3-week time interval, and that rigorous SARS-CoV-2 infection prevention and control measures be continued in dialysis units until vaccine efficacy is proven.