التفاصيل البيبلوغرافية
| العنوان: |
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. |
| المؤلفون: |
King, Thomas H., Kemmler, Charles B., Guo, Zhimin, Mann, Derrick, Lu, Yingnian, Coeshott, Claire, Gehring, Adam J., Bertoletti, Antonio, Ho, Zi Z., Delaney, William, Gaggar, Anuj, Subramanian, G. Mani, McHutchison, John G., Shrivastava, Shikha, Lee, Yu-Jin L., Kottilil, Shyamasundaran, Bellgrau, Donald, Rodell, Timothy, Apelian, David |
| المصدر: |
PLoS ONE; Jul2014, Vol. 9 Issue 7, p1-17, 17p |
| مصطلحات موضوعية: |
YEAST, HEPATITIS B virus, VIRAL vaccines, T cells, LABORATORY mice, EPITOPES, IMMUNOTHERAPY |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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