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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4+, and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). 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 T helper (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 (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure. [Display omitted] •Two doses of SARS-CoV-2 vaccine induce weak B cells in people on hemodialysis (HD)•People on HD generate less mature B cells after two vaccine doses•A third immunization in HD robustly boosts B and CD4+ T cell responses•CD4+ T cell profile in HD is skewed toward CCR6, CXCR6, PD-1, HLA-DR, and TNFα/IL-2 Sannier et al. describe specific humoral, B, and T cell responses in people on hemodialysis (HD) after mRNA vaccination against SARS-CoV-2. Three doses are critical to elicit robust antibody, B cell, and CD8+ T cell responses. CD4+ T cell profile is skewed toward TNF/IL-2, CCR6, CXCR6, PD-1, and HLA-DR expression.