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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, ISSN: 1932-6203, Vol: 9, Issue: 7, Page: e101904
2014
  • 61
    Citations
  • 0
    Usage
  • 71
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    61
    • Citation Indexes
      58
    • Clinical Citations
      1
      • PubMed Guidelines
        1
    • Patent Family Citations
      1
      • Patent Families
        1
    • Policy Citations
      1
      • Policy Citation
        1
  • Captures
    71

Article 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. © 2014 King et al.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84904625418&origin=inward; http://dx.doi.org/10.1371/journal.pone.0101904; http://www.ncbi.nlm.nih.gov/pubmed/25051027; https://dx.plos.org/10.1371/journal.pone.0101904.g006; http://dx.doi.org/10.1371/journal.pone.0101904.g006; https://dx.plos.org/10.1371/journal.pone.0101904.t002; http://dx.doi.org/10.1371/journal.pone.0101904.t002; https://dx.plos.org/10.1371/journal.pone.0101904.g003; http://dx.doi.org/10.1371/journal.pone.0101904.g003; https://dx.plos.org/10.1371/journal.pone.0101904.g004; http://dx.doi.org/10.1371/journal.pone.0101904.g004; https://dx.plos.org/10.1371/journal.pone.0101904; https://dx.plos.org/10.1371/journal.pone.0101904.g005; http://dx.doi.org/10.1371/journal.pone.0101904.g005; https://dx.plos.org/10.1371/journal.pone.0101904.t001; http://dx.doi.org/10.1371/journal.pone.0101904.t001; https://dx.plos.org/10.1371/journal.pone.0101904.g001; http://dx.doi.org/10.1371/journal.pone.0101904.g001; https://dx.plos.org/10.1371/journal.pone.0101904.g008; http://dx.doi.org/10.1371/journal.pone.0101904.g008; https://dx.plos.org/10.1371/journal.pone.0101904.g007; http://dx.doi.org/10.1371/journal.pone.0101904.g007; https://dx.plos.org/10.1371/journal.pone.0101904.g002; http://dx.doi.org/10.1371/journal.pone.0101904.g002; https://dx.doi.org/10.1371/journal.pone.0101904.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g004; https://dx.doi.org/10.1371/journal.pone.0101904.g006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g006; https://dx.doi.org/10.1371/journal.pone.0101904.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g002; https://dx.doi.org/10.1371/journal.pone.0101904; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101904; https://dx.doi.org/10.1371/journal.pone.0101904.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g003; https://dx.doi.org/10.1371/journal.pone.0101904.g008; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g008; https://dx.doi.org/10.1371/journal.pone.0101904.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.t001; https://dx.doi.org/10.1371/journal.pone.0101904.t002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.t002; https://dx.doi.org/10.1371/journal.pone.0101904.g007; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g007; https://dx.doi.org/10.1371/journal.pone.0101904.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g005; https://dx.doi.org/10.1371/journal.pone.0101904.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0101904.g001; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101904; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0101904&type=printable; http://dx.plos.org/10.1371/journal.pone.0101904.g008; http://dx.plos.org/10.1371/journal.pone.0101904.g005; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0101904; http://dx.plos.org/10.1371/journal.pone.0101904.g003; http://dx.plos.org/10.1371/journal.pone.0101904.g002; http://dx.plos.org/10.1371/journal.pone.0101904.g001; http://dx.plos.org/10.1371/journal.pone.0101904.g004; http://dx.plos.org/10.1371/journal.pone.0101904.t001; http://dx.plos.org/10.1371/journal.pone.0101904.g006; http://dx.plos.org/10.1371/journal.pone.0101904; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0101904; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0101904&type=printable; http://dx.plos.org/10.1371/journal.pone.0101904.t002; http://dx.plos.org/10.1371/journal.pone.0101904.g007

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; Kim J. Hasenkrug

Public Library of Science (PLoS)

Multidisciplinary

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