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PLoS One. 2014 Jul 22;9(7):e101904. doi: 10.1371/journal.pone.0101904. eCollection 2014.

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.

Author information

1
GlobeImmune, Inc., Louisville, Colorado, United States of America.
2
Molecular Microbiology and Immunology & Saint Louis University Liver Center, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America; Agency for Science, Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore, Singapore.
3
Agency for Science, Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore, Singapore.
4
Gilead Sciences Inc., Foster City, California, United States of America.
5
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
6
GlobeImmune, Inc., Louisville, Colorado, United States of America; Integrated Department of Immunology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

Abstract

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.

PMID:
25051027
PMCID:
PMC4106793
DOI:
10.1371/journal.pone.0101904
[Indexed for MEDLINE]
Free PMC Article

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