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Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.
Schrezenmeier, Eva; Rincon-Arevalo, Hector; Jens, Annika; Stefanski, Ana-Luisa; Hammett, Charlotte; Osmanodja, Bilgin; Koch, Nadine; Zukunft, Bianca; Beck, Julia; Oellerich, Michael; Proß, Vanessa; Stahl, Carolin; Choi, Mira; Bachmann, Friederike; Liefeldt, Lutz; Glander, Petra; Schütz, Ekkehard; Bornemann-Kolatzki, Kirsten; López Del Moral, Covadonga; Schrezenmeier, Hubert; Ludwig, Carolin; Jahrsdörfer, Bernd; Eckardt, Kai-Uwe; Lachmann, Nils; Kotsch, Katja; Dörner, Thomas; Halleck, Fabian; Sattler, Arne; Budde, Klemens.
  • Schrezenmeier E; Department of Nephrology and Medical Intensive Care and.
  • Rincon-Arevalo H; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Jens A; BIH Charité Clinician Scientist Program, BIH Biomedical Innovation Academy, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Stefanski AL; Department of Nephrology and Medical Intensive Care and.
  • Hammett C; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Osmanodja B; German Rheumatism Research Centre Berlin (DRFZ), Berlin, Germany.
  • Koch N; Cellular Immunology and Immunogenetics Group, Faculty of Medicine, Institute of Medical Research, University of Antioquia (UdeA), Medellín, Colombia.
  • Zukunft B; Department of Nephrology and Medical Intensive Care and.
  • Beck J; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Oellerich M; German Rheumatism Research Centre Berlin (DRFZ), Berlin, Germany.
  • Proß V; Department of Nephrology and Medical Intensive Care and.
  • Stahl C; Department of Nephrology and Medical Intensive Care and.
  • Choi M; Department of Nephrology and Medical Intensive Care and.
  • Bachmann F; Department of Nephrology and Medical Intensive Care and.
  • Liefeldt L; Department of Clinical Pharmacology, Universitätsmedizin Göttingen, Göttingen, Germany.
  • Glander P; Chronix Biomedical GmbH, Göttingen, Germany.
  • Schütz E; Department of Clinical Pharmacology, Universitätsmedizin Göttingen, Göttingen, Germany.
  • Bornemann-Kolatzki K; Department for General and Visceral Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • López Del Moral C; Department for General and Visceral Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schrezenmeier H; Department of Nephrology and Medical Intensive Care and.
  • Ludwig C; Department of Nephrology and Medical Intensive Care and.
  • Jahrsdörfer B; Department of Nephrology and Medical Intensive Care and.
  • Eckardt KU; Department of Nephrology and Medical Intensive Care and.
  • Lachmann N; Chronix Biomedical GmbH, Göttingen, Germany.
  • Kotsch K; Chronix Biomedical GmbH, Göttingen, Germany.
  • Dörner T; Department of Nephrology and Medical Intensive Care and.
  • Halleck F; Institute of Transfusion Medicine, Ulm University, Ulm, Germany.
  • Sattler A; Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
  • Budde K; Institute of Transfusion Medicine, Ulm University, Ulm, Germany.
JCI Insight ; 7(9)2022 May 09.
Article in English | MEDLINE | ID: covidwho-1765224
ABSTRACT
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Vaccines / COVID-19 / Antimetabolites Topics: Vaccines Limits: Humans Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Vaccines / COVID-19 / Antimetabolites Topics: Vaccines Limits: Humans Language: English Year: 2022 Document Type: Article