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 HBcAg18-27-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.

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Keywords Cross-presentation, HBV, Human dendritic cell, Synthetic long peptide vaccine, T cell
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Journal The Journal of Infectious Diseases
Dou, Y. (Yingying), van Montfoort, N, van den Bosch, A, de Man, R.A, Zom, G.G. (Gijs G.), Krebber, W.-J. (Willem-Jan), … Woltman, A.M. (2018). HBV-derived synthetic long peptide can boost CD4+ and CD8+ T-cell responses in chronic HBV patients ex vivo. The Journal of Infectious Diseases, 217(5), 827–839. doi:10.1093/infdis/jix614