Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients

Abstract

Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4/39 and 1/39 transplanted individuals showed IgA and IgG seroconversion at day 8±1 after booster immunization with minor changes until day 23±5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared to controls and dialysis patients, accompanied by a broad impairment in effector cytokine production, memory differentiation and activation-related signatures. Spike-specific CD8 + T cell responses were less abundant than their CD4 + counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk to develop severe COVID-19.

Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients

“…The only available data after complete vaccination comes from three studies. In comparison to them, our results show percentages of T-cell activation that are closer to the general population (88.2%) 24 than to those in kidney transplant recipients (5.13%-35%) 25,26 . Even so, this is an inadequate response, which is consistent with the response reported after hepatitis B virus vaccination of maintenance hemodialysis patients 27 .…”

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.…”

“…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.…”

Heterologous ChAdOx1 nCoV-19/BNT162b2 Prime-Boost Vaccination Induces Strong Humoral Responses among Health Care Workers

“…Since we investigated humoral responses following SARS-CoV-2 vaccination in health care workers, most individuals were between 25–65 years of age and in a comparably good general state of health. Since we, and others, have shown significantly reduced immunogenicity of SARS-CoV-2 vaccines in immunosuppressed patients, patients on dialysis, or even elderly individuals, our results cannot be transferred unrestricted to the general population [ 20 , 21 , 22 ]. Results have to be separately confirmed by including these vulnerable subpopulations into further studies.…”