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Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients
Arne Sattler, Eva Schrezenmeier, Ulrike A. Weber, Alexander Potekhin, Friederike Bachmann, Henriette Straub-Hohenbleicher, Klemens Budde, Elena Storz, Vanessa Proß, Yasmin Bergmann, Linda M.L. Thole, Caroline Tizian, Oliver Hölsken, Andreas Diefenbach, Hubert Schrezenmeier, Bernd Jahrsdörfer, Tomasz Zemojtel, Katharina Jechow, Christian Conrad, Sören Lukassen, Diana Stauch, Nils Lachmann, Mira Choi, Fabian Halleck, Katja Kotsch
Arne Sattler, Eva Schrezenmeier, Ulrike A. Weber, Alexander Potekhin, Friederike Bachmann, Henriette Straub-Hohenbleicher, Klemens Budde, Elena Storz, Vanessa Proß, Yasmin Bergmann, Linda M.L. Thole, Caroline Tizian, Oliver Hölsken, Andreas Diefenbach, Hubert Schrezenmeier, Bernd Jahrsdörfer, Tomasz Zemojtel, Katharina Jechow, Christian Conrad, Sören Lukassen, Diana Stauch, Nils Lachmann, Mira Choi, Fabian Halleck, Katja Kotsch
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Research Article Immunology

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

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Abstract

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, 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 of 39 and 1 of 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 with those in controls and dialysis patients and this was 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 of developing severe COVID-19.

Authors

Arne Sattler, Eva Schrezenmeier, Ulrike A. Weber, Alexander Potekhin, Friederike Bachmann, Henriette Straub-Hohenbleicher, Klemens Budde, Elena Storz, Vanessa Proß, Yasmin Bergmann, Linda M.L. Thole, Caroline Tizian, Oliver Hölsken, Andreas Diefenbach, Hubert Schrezenmeier, Bernd Jahrsdörfer, Tomasz Zemojtel, Katharina Jechow, Christian Conrad, Sören Lukassen, Diana Stauch, Nils Lachmann, Mira Choi, Fabian Halleck, Katja Kotsch

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Figure 2

Quantitative features of spike-reactive T cells.

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Quantitative features of spike-reactive T cells.
(A) PBMCs were stimulat...
(A) PBMCs were stimulated with spike (left) or CEF (right) peptide mix for 16 hours, as indicated. Specific CD4+ T cells were identified and quantified by FACS based on coexpression of CD154 and CD137. Depicted are percentages of HCs (n = 39), KTx recipients (n = 39), and HD patients (n = 26) with positive CD4+ T cell responses (responders: Fisher’s exact test, respectively). (B) Frequencies of specific Th cells within responders. HC: spike, n = 39; CEF, n = 35; KTx: spike, n = 36; CEF, n = 34; HD: spike, n = 26; CEF, n = 24. Kruskal-Wallis test. (C) Portions of spike-specific Th cells in KTx patients showing IgA and/or IgG responses (+, n = 8) or not (–, n = 31; Mann-Whitney U test) until day 23 ± 5. (D) Antigen-specific CD8+ T cells were identified within PBMCs based on coexpression of CD137 and IFN-γ. Depicted are percentages within HCs (n = 39), KTx recipients (n = 39), and HD patients (n = 26) with positive CD8+ T cell responses (responders) toward spike (left, Fisher’s exact test) or CEF (right, Fisher’s exact test) stimulation. (E) Frequencies of spike-specific (left, Mann-Whitney U test) or CEF-specific CD8+ T cells (right, Kruskal-Wallis test) within responders. HC: spike, n = 18; CEF, n = 31; KTx: spike, n = 2. CEF, n = 30; HD: spike, n = 8; CEF, n = 22. Graphs show mean ± SD.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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