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
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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