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

• Published in: The Journal of clinical investigation Vol. 131; no. 14; pp. 1 - 11
• Main Authors: Sattler, Arne, Schrezenmeier, Eva, Weber, Ulrike A, Potekhin, Alexander, Bachmann, Friederike, Straub-Hohenbleicher, Henriette, Budde, Klemens, Storz, Elena, Proß, Vanessa>, Bergmann, Yasmin, Thole, Linda M L, Tizian, Caroline, Hölsken, Oliver, Diefenbach, Andreas, Schrezenmeier, Hubert, Jahrsdörfer, Bernd, Zemojtel, Tomasz, Jechow, Katharina, Conrad, Christian, Lukassen, Sören, Stauch, Diana, Lachmann, Nils, Choi, Mira, Halleck, Fabian, Kotsch, Katja
• Format: Journal Article
• Language: English
• Published: Ann Arbor American Society for Clinical Investigation 01-07-2021
• Subjects: Antibodies; Antigens; Biomedical research; Cardiovascular disease; CD4 antigen; CD8 antigen; Cell-mediated immunity; Coronaviruses; COVID-19; COVID-19 vaccines; Cytokines; Graft rejection; Helper cells; Hemodialysis; Histocompatibility antigen HLA; Humoral immunity; Immunoglobulin A; Immunoglobulin G; Infections; Influenza; Kidney transplantation; Kidney transplants; Lymphocytes; Lymphocytes T; Memory cells; Mortality; mRNA; Pandemics; Patients; Peptides; Renal insufficiency; Seroconversion; Severe acute respiratory syndrome coronavirus 2; Vaccines
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI150175.

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.