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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere101904
JournalPloS one
Volume9
Issue number7
DOIs
StatePublished - Jul 22 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this