Robust hepatitis B vaccine-reactive T cell responses in failed humoral immunity

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 an...

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Bibliographic Details
Main Authors: Gounwa Awad, Toralf Roch, Ulrik Stervbo, Sviatlana Kaliszczyk, Anna Stittrich, Jan Hörstrup, Ocan Cinkilic, Heiner Appel, Larysa Natrus, Ludmila Gayova, Felix Seibert, Frederic Bauer, Timm Westhoff, Mikalai Nienen, Nina Babel
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:Molecular Therapy: Methods & Clinical Development
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Online Access:http://www.sciencedirect.com/science/article/pii/S2329050121000528
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Summary: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.
ISSN:2329-0501