Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients
Arne Sattler, … , Fabian Halleck, Katja Kotsch
Arne Sattler, … , Fabian Halleck, Katja Kotsch
Published June 8, 2021
Citation Information: J Clin Invest. 2021;131(14):e150175. https://doi.org/10.1172/JCI150175.
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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

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 4

Characteristics of the spike-specific Th cell response with respect to memory formation and ex vivo proliferation/activation.

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Characteristics of the spike-specific Th cell response with respect to m...
Spike- or CEF-specific CD154+CD137+ Th cells were assessed for their memory or effector phenotype with CD45RO+CD62L– identifying TEM, CD45RO+CD62L+ central memory (TCM), and CD45RO–CD62L– effector-like T cells (TEff). (A) Exemplary staining of spike-specific vs. total Th cells from a healthy donor (left) and subset comparison based on the respective mean values for each group (right). (B) Data of spike- and CEF-specific TEM (left panels; spike/CEF: ANOVA) and TEff (right panels; spike/CEF: ANOVA) with n as in Figure 2B. Antigen-specific Th cells were further characterized for (C) ex vivo proliferation based on Ki67 expression (spike/CEF: Kruskal-Wallis test), (D) expression of the activation/exhaustion marker PD1 (spike: ANOVA, CEF: Kruskal-Wallis test), or (E) costimulatory receptor CD28 (spike/CEF: Kruskal-Wallis test) with exemplary overlays of spike-specific vs. total T cells (left) and summarized data for all groups (right) with n as in Figure 2B. SSC-A, side scatter area. Graphs show mean ± SD.