Abstract
Patients with kidney failure are at increased risk for SARS-CoV-2 infection making effective vaccinations a critical need. It is not known how well mRNA vaccines induce B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 35 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. The frequency and absolute number of antigen-specific circulating plasmablasts in the cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, these data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells. Thus, there is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.
Highlights
COVID-19 leads to a high morbidity and mortality especially among patients with kidney failure [1]
kidney transplant recipients (KTR) were on a uniform immunosuppressive regimen with mycophenolate mofetil (MMF) in 39/40, steroid in 37/40 and calcineurin inhibitor (CNI) in 37/40 patients
We investigated the distribution of anti-BNT162b2 antigen-specific B cell responses among healthy controls (HC) in comparison to Dialysis patients (DP) and KTR as prototypes for differentially immunocompromised patients
Summary
COVID-19 leads to a high morbidity and mortality especially among patients with kidney failure [1]. Dialysis patients (DP) and kidney transplant recipients (KTR) are at increased risk of developing COVID-19 and experiencing a severe infection, due to exposure risk in the health care system, their comorbidities, and their impaired immune function from kidney failure or immunosuppressive medications. For this vulnerable population, vaccination is of the utmost importance. Whereas numerous studies have addressed the consequences of conventional vaccines on B and plasma cells [6,7,8] and corresponding Ig levels, nothing is known yet about the B lineage consequences in response to an mRNA vaccine among healthy controls and immunocompromised patients
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