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.
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 immunother...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0101904 |
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| author | Thomas H King Charles B Kemmler Zhimin Guo Derrick Mann Yingnian Lu Claire Coeshott Adam J Gehring Antonio Bertoletti Zi Z Ho William Delaney Anuj Gaggar G Mani Subramanian John G McHutchison Shikha Shrivastava Yu-Jin L Lee Shyamasundaran Kottilil Donald Bellgrau Timothy Rodell David Apelian |
| author_facet | Thomas H King Charles B Kemmler Zhimin Guo Derrick Mann Yingnian Lu Claire Coeshott Adam J Gehring Antonio Bertoletti Zi Z Ho William Delaney Anuj Gaggar G Mani Subramanian John G McHutchison Shikha Shrivastava Yu-Jin L Lee Shyamasundaran Kottilil Donald Bellgrau Timothy Rodell David Apelian |
| author_sort | Thomas H King |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e27258ef8564bc4a5d1fac67125fcb8 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7e27258ef8564bc4a5d1fac67125fcb82025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10190410.1371/journal.pone.0101904A 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.Thomas H KingCharles B KemmlerZhimin GuoDerrick MannYingnian LuClaire CoeshottAdam J GehringAntonio BertolettiZi Z HoWilliam DelaneyAnuj GaggarG Mani SubramanianJohn G McHutchisonShikha ShrivastavaYu-Jin L LeeShyamasundaran KottililDonald BellgrauTimothy RodellDavid ApelianChronic 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.https://doi.org/10.1371/journal.pone.0101904 |
| spellingShingle | Thomas H King Charles B Kemmler Zhimin Guo Derrick Mann Yingnian Lu Claire Coeshott Adam J Gehring Antonio Bertoletti Zi Z Ho William Delaney Anuj Gaggar G Mani Subramanian John G McHutchison Shikha Shrivastava Yu-Jin L Lee Shyamasundaran Kottilil Donald Bellgrau Timothy Rodell David Apelian 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://doi.org/10.1371/journal.pone.0101904 |
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