HBV-Derived Synthetic Long Peptide Can Boost CD4(+) and CD8(+) T-Cell Responses in Chronic HBV Patients Ex Vivo

BACKGROUND: Vaccination with synthetic long peptides (SLP) is a promising new treatment strategy for chronic hepatitis B virus (CHB). SLP can induce broad T-cell responses for all HLA types. Here we investigated the ability of a prototype HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients ex vivo. METHODS: HBc-SLP was used to assess cross-presentation by monocyte-derived dendritic cells (moDC) and BDCA1(+) blood myeloid DC (mDC) to engineered HBV-specific CD8(+) T cells. Autologous SLP-loaded and toll-like receptor (TLR)-stimulated DC were used to activate patient HBc-specific CD8(+) and CD4(+) T cells. RESULTS: HBV-SLP was cross-presented by moDC, which was further enhanced by adjuvants. Patient-derived SLP-loaded moDC significantly increased autologous HBcAg(18-27)-specific CD8(+) T cells and CD4(+) T cells ex vivo. HBV-specific T cells were functional as they synthesized tumor necrosis factor-alpha and interferon-gamma. In 6/7 of patients blockade of PD-L1 further increased SLP effects. Also, importantly, patient-derived BDCA1(+) mDC cross-presented and activated autologous T-cell responses ex vivo. CONCLUSIONS: As a proof of concept, we showed a prototype HBc-SLP can boost T-cell responses in patients ex vivo. These results pave the way for the development of a therapeutic SLP-based vaccine to induce effective HBV-specific adaptive immune responses in CHB patients.