A Whole Recombinant Yeast-Based Therapeutic Vaccine Elicits HBV X, S and Core Specific T Cells in Mice and Activates Human T Cells Recognizing Epitopes Linked to Viral Clearance
Autor: | G. Mani Subramanian, John G. McHutchison, Anuj Gaggar, Charles B. Kemmler, David Apelian, Timothy C. Rodell, Thomas H. King, Zhimin Guo, Adam J. Gehring, Shikha Shrivastava, Zi Z. Ho, Shyamasundaran Kottilil, Donald Bellgrau, William E. Delaney, Claire Coeshott, Derrick Mann, Yu-Jin Lee, Yingnian Lu, Antonio Bertoletti |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
medicine.medical_treatment
T-Lymphocytes lcsh:Medicine Mice SCID Biochemistry Medicine and Health Sciences Cytotoxic T cell Viral Regulatory and Accessory Proteins lcsh:Science Cells Cultured Mice Inbred BALB C Multidisciplinary ELISPOT Viral Core Proteins Liver Neoplasms Vaccination medicine.anatomical_structure Infectious Diseases Female Research Article Biotechnology Hepatitis B virus T cell Inflammatory Diseases Immunology Gastroenterology and Hepatology Saccharomyces cerevisiae Microbiology Interferon-gamma Immune system Cross-Priming Hepatitis B Chronic Antigen medicine Genetics Animals Humans Hepatitis B Vaccines Antigen-presenting cell Molecular Biology Cell Proliferation business.industry lcsh:R Biology and Life Sciences Immunotherapy Cell Biology Dendritic Cells Virology Mice Inbred C57BL Trans-Activators Interleukin-2 lcsh:Q business Viral Fusion Proteins CD8 |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 7, p e101904 (2014) |
ISSN: | 1932-6203 |
Popis: | Chronic hepatitis B infection (CHB) is characterized by sub-optimal T cell responses to viral antigens. A therapeutic vaccine capable of restoring these immune responses could potentially improve HBsAg seroconversion rates in the setting of direct acting antiviral therapies. A yeast-based immunotherapy (Tarmogen) platform was used to make a vaccine candidate expressing hepatitis B virus (HBV) X, surface (S), and Core antigens (X-S-Core). Murine and human immunogenicity models were used to evaluate the type and magnitude of HBV-Ag specific T cell responses elicited by the vaccine. C57BL/6J, BALB/c, and HLA-A*0201 transgenic mice immunized with yeast expressing X-S-Core showed T cell responses to X, S and Core when evaluated by lymphocyte proliferation assay, ELISpot, intracellular cytokine staining (ICS), or tumor challenge assays. Both CD4+ and CD8+ T cell responses were observed. Human T cells transduced with HBc18–27 and HBs183–91 specific T cell receptors (TCRs) produced interferon gamma (IFNγ following incubation with X-S-Core-pulsed dendritic cells (DCs). Furthermore, stimulation of peripheral blood mononuclear cells (PBMCs) isolated from CHB patients or from HBV vaccine recipients with autologous DCs pulsed with X-S-Core or a related product (S-Core) resulted in pronounced expansions of HBV Ag-specific T cells possessing a cytolytic phenotype. These data indicate that X-S-Core-expressing yeast elicit functional adaptive immune responses and supports the ongoing evaluation of this therapeutic vaccine in patients with CHB to enhance the induction of HBV-specific T cell responses. |
Databáze: | OpenAIRE |
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