Chronic Hepatitis B Virus (HBV) infections decrease the activity of HBV-specific T lymphocytes. Immunotherapy has the potential to restore HBV-specific T cell responses, which are required for long-term illness remission and the induction of a functional cure. Chimigen® Molecules are antigen(s) fusion proteins with the Fc segment of a xenotypic antibody that are designed to target particular receptors on dendritic cells (DCs). The study reports the synthesis and pre-clinical assessment of Chimigen® HBV (C-HBV), which is made in insect cells and contains HBV PreS1 and PreS2 peptide fragments, HBV core, and murine Fc. The FcαRII (CD32) and the mannose receptor (CD206) were reliant on the C-HBV interaction with immature DCs and internalisation of endocytosis and led to enhanced surface expression for MHC I and for MHC II. C-HBV caused a robust T-cell proliferation and increased the production of IFN-α, TNF-α, perforin and granzyme B in both CD4+ and CD8+ T subsets after exposure of human T cells from HBV uninfected healthy or chronically infected donors to C-HBV-pulsed mature DCs ex vivo. C-HBV-activated cell re-stimulation of T lymphocytes in both CD4+ and CD8+ populations from chronically infected donors with HBV PreS1/PreS2 and overlapping core peptides.
C-HBV activation of PBMCs from chronically HBV-infected patients increased granzyme B production by CD4+CD25 T responder (Tresp) cells, which was followed by an increase in Annexin V staining on CD4+CD25+ T regulatory (Treg) cell phenotype, consistent with apoptosis.
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