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

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

doi:10.1016/j.omtm.2021.03.012

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.

Authors

Gounwa Awad¹, Toralf Roch^{1

2}, Ulrik Stervbo¹, Sviatlana Kaliszczyk^{1

2}, Anna Stittrich^{2

3}, Jan Hörstrup⁴, Ocan Cinkilic⁵, Heiner Appel⁶, Larysa Natrus⁷, Ludmila Gayova⁷, Felix Seibert¹, Frederic Bauer¹, Timm Westhoff¹, Mikalai Nienen^{2

3

8}, Nina Babel^{1

2}

Affiliations

¹ University Hospital Marien Hospital Herne, Ruhr-University of Bochum, Bochum, Germany.
² BIH 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.
³ Labor Berlin - Charité Vivantes GmbH, Berlin, Germany.
⁴ KfH Kuratorium für Dialyse und Nierentransplantation e.V., Berlin, Germany.
⁵ Dialyse Schwerte, Schwerte, Germany.
⁶ Dialysezentrum Hamm, Hamm, Germany.
⁷ Bogomolets National Medical University, Kyiv, Ukraine.
⁸ Institute 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.

Keywords: T cell memory; failed Hepatitis B vaccination; polyfunctional T cells.