Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients

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.

Vaccine serologic responses among transplant patients associate with COVID-19 infection and T peripheral helper cells

“…In addition, we provide the first correlation of these responses to quantitative analyses of baseline T and B cell subsets. Consistent with findings of other investigators (16)(17)(18)(19)(20)(21)(22)(23)(24)(25), we show that COVID-19-naive heart and lung transplant recipients have a profound reduction in neutralizing antibodies against SARS-CoV-2 spike protein and receptor binding domain (RBD)-specific immunoglobulin levels after both prime and boost vaccine doses. However, transplant recipients who had COVID-19 infection prior to vaccination displayed neutralizing antibodies to SARS-CoV-2 at baseline that increased following vaccination.…”

“…3A and 3C). Delayed responses to SARS-CoV-2 vaccination have also been reported in kidney transplant and chronic dialysis patients (20,36). The association between IgG responses and TPH cells may offer a clue, as these cells have been implicated in extrafollicular B cell differentiation and maintenance (37) and COVID-19 infection induces expansion of TPH cells (38) and increases in non-germinal center B cell responses (39).…”

“…The copyright holder for this preprint this version posted July 14, 2021. ; https://doi.org/10.1101/2021.07.11.21260338 doi: medRxiv preprint vaccination in transplant recipients indicate major impairments in vaccine-induced humoral and cellular immunity (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Whether transplant recipients are uniquely vulnerable to more transmissible viral strains with spike protein variants, which are rising in prevalence globally, remains unclear.…”

Implications of defective immune responses in SARS-CoV-2–vaccinated organ transplant recipients

“…Inherited or acquired defects in any of these interrelated immunological processes could potentially disrupt development of protective immunity in response to the vaccine, especially the SARS-CoV-2 vaccines. In a recent issue of Science Immunology, Rincon-Arevalo and colleagues add to the emerging literature documenting that one specific at-risk population for SARS-CoV-2 vaccine failure is organ transplant recipients (1). Transplant recipients require life-long immunosuppression regimens, which commonly include some combination of a calcineurin inhibitor (such as tacrolimus), a steroid, and/or an anti-metabolite (such as mycophenolic acid or mycophenolate mofetil (MMF)).…”

“…Several publications from 2021 have now documented that immunosuppressed transplant recipients do not routinely develop protective antibody titers following full vaccination with any of the approved SARS-CoV-2 mRNA (2) or viral vector (3) vaccines. Associative evidence suggests that use of MMF, an anti-proliferative agent that affects T and B cells, contributes to the lack of response (1,2). A more detailed understanding of the immunosuppression-induced defects following SARS-CoV-2 vaccination is needed in order to guide new approaches to induce protective immunity in this at-risk population.…”