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Abstract Details
Robust hepatitis B vaccine-reactive T cell responses in failed humoral immunity
Mol Ther Methods Clin Dev. 2021 Mar 23;21:288-298. doi:10.1016/j.omtm.2021.03.012.eCollection 2021 Jun 11.
Gounwa Awad1, Toralf Roch12, Ulrik Stervbo1, Sviatlana Kaliszczyk12, Anna Stittrich23, Jan Hörstrup4, Ocan Cinkilic5, Heiner Appel6, Larysa Natrus7, Ludmila Gayova7, Felix Seibert1, Frederic Bauer1, Timm Westhoff1, Mikalai Nienen238, Nina Babel12
Author information
1University Hospital Marien Hospital Herne, Ruhr-University of Bochum, Bochum, Germany.
2BIH Center for Regenerative Therapies, Charité - University Medicine Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany.
3Labor Berlin - Charité Vivantes GmbH, Berlin, Germany.
4KfH Kuratorium für Dialyse und Nierentransplantation e.V., Berlin, Germany.
5Dialyse Schwerte, Schwerte, Germany.
6Dialysezentrum Hamm, Hamm, Germany.
7Bogomolets National Medical University, Kyiv, Ukraine.
8Institute for Medical Immunology, Charité - University Medicine Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany.
Abstract
While virus-specific antibodies are broadly recognized as correlates of protection, virus-specific T cells are important for direct clearance of infected cells. Failure to generate hepatitis B virus (HBV)-specific antibodies is well-known in patients with end-stage renal disease. However, whether and to what extent HBV-specific cellular immunity is altered in this population and how it influences humoral immunity is not clear. To address it, we analyzed HBV-reactive T cells and antibodies in hemodialysis patients post vaccination. 29 hemodialysis patients and 10 healthy controls were enrolled in a cross-sectional study. Using multiparameter flow cytometry, HBV-reactive T cells were analyzed and functionally dissected based on granzyme B, interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and IL-4 expression. Importantly, HBV-reactive CD4+ T cells were detected not only in all patients with sufficient titers but also in 70% of non-responders. Furthermore, a correlation between the magnitude of HBV-reactive CD4+ T cells and post-vaccination titers was observed. In summary, our data showed that HBV-reactive polyfunctional T cells were present in the majority of hemodialysis patients even if humoral immunity failed. Further studies are required to confirm their in vivo antiviral capacity. The ability to induce vaccine-reactive T cells paves new ways for improved vaccination and therapy protocols.