| 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. |
| Authors: |
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 |
| Source: |
PLoS ONE, Vol 9, Iss 7, p e101904 (2014) |
| Publisher Information: |
Public Library of Science (PLoS), 2014. |
| Publication Year: |
2014 |
| Collection: |
LCC:Medicine; LCC:Science |
| Subject Terms: |
Medicine; Science |
| 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0101904 |
| Access URL: |
https://doaj.org/article/7e27258ef8564bc4a5d1fac67125fcb8 |
| Accession Number: |
edsdoj.7e27258ef8564bc4a5d1fac67125fcb8 |
| Database: |
Directory of Open Access Journals |