Impaired Humoral and Cellular Immunity after SARS-CoV2 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 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 prime-boost vaccination with BNT162b2. 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. Signs of alloreactivity promoted by BNT162b2 were not documented within the observation period. 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.

Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients

“…Only 68% of seropositive patients showed neutralizing antibodies. Smaller cohorts representing KTRs failed to demonstrate any neutralizing antibody capacity in these patients 11,12 . In fact, the presence and in particular the titer levels of the neutralizing antibodies correlate with efficient protection against COVID‐19 infection and more importantly against novel virus variants such as B.1.617.2 and B.1.351 13,14 .…”

“…Smaller cohorts representing KTRs failed to demonstrate any neutralizing antibody capacity in these patients. 11 , 12 In fact, the presence and in particular the titer levels of the neutralizing antibodies correlate with efficient protection against COVID‐19 infection and more importantly against novel virus variants such as B.1.617.2 and B.1.351. 13 , 14 Thus, significantly lower neutralizing antibody titers in KTRs as shown in the present study may confer lower protection against COVID‐19 infection especially those caused by SARS‐CoV‐2 variants.…”

“…Recent studies have shown that the specific T cell immune response is also impaired in KTRs compared to controls or dialysis patients. 4 , 12 Interestingly, an anti‐spike‐specific T cell response after SARS‐CoV‐2 vaccination was detected in half of the KTRs and even in those with no detectable humoral immune response. 12 Thus, one can assume that at least some of the patients with no significant humoral immune response may have a sufficient T cell response to prevent severe COVID‐19 infection.…”

“… 4 , 12 Interestingly, an anti‐spike‐specific T cell response after SARS‐CoV‐2 vaccination was detected in half of the KTRs and even in those with no detectable humoral immune response. 12 Thus, one can assume that at least some of the patients with no significant humoral immune response may have a sufficient T cell response to prevent severe COVID‐19 infection. However, this needs to be investigated in large outcome studies.…”

SARS-CoV-2 Infection in Fully Vaccinated Individuals of Old Age Strongly Boosts the Humoral Immune Response

“…Despite these positive effects of vaccination, however, there are still groups of people in whom the vaccination response is reduced. These include patients with certain diseases or treatment associated with a reduced immune response, such as renal failure requiring dialysis or immunosuppressive therapy after organ transplantation (10)(11)(12). Notably, the vaccine response is also reduced in persons of advanced age.…”