Robust hepatitis B vaccine-reactive T cell responses in failed humoral immunity
| Autor: | Timm H. Westhoff, Ludmila Gayova, Gounwa Awad, L.V. Natrus, Ocan Cinkilic, Jan Hörstrup, Heiner Appel, Anna Stittrich, Ulrik Stervbo, Felix S. Seibert, Nina Babel, Toralf Roch, Frederic Bauer, Mikalai Nienen, Sviatlana Kaliszczyk |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cellular immunity Hepatitis B vaccine T cell Population T cell memory QH426-470 medicine.disease_cause 03 medical and health sciences polyfunctional T cells 0302 clinical medicine failed Hepatitis B vaccination Genetics Medicine education Molecular Biology Hepatitis B virus education.field_of_study biology QH573-671 business.industry Vaccination 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Humoral immunity Immunology biology.protein Molecular Medicine Original Article Antibody business Cytology |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 21, Iss, Pp 288-298 (2021) Molecular Therapy. Methods & Clinical Development |
| ISSN: | 2329-0501 |
| Popis: | 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. Graphical Abstract Despite HBV vaccination failure in end-stage renal disease (ESRD), HBV-reactive T cells are generated in about 70% of ESRD-vaccinees. Further, the non-responder group demonstrated polyfunctional HBV-reactive CD4+ T cells suggesting their potential anti-viral capacities. The ability to induce vaccine-reactive T cells paves new ways for improved vaccination and therapy protocols. |
| Databáze: | OpenAIRE |
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