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HBV-derived synthetic long peptide can boost CD4 + and CD8 + T cell responses in chronic HBV patients ex vivo
Yingying Dou Nadine van Montfoort Aniek van den Bosch Robert A de Man Gijs G Zom Willem-Jan Krebber Cornelis JM Melief Sonja I Buschow Andrea M Woltman
The Journal of Infectious Diseases, jix614, https://doi.org/10.1093/infdis/jix614
Published:
06 December 2017
Abstract
Background
Vaccination with Synthetic Long Peptides (SLP®) is a promising new treatment strategy for chronic HBV (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 DC (moDC) and BDCA1 + blood myeloid DC (mDC) to engineered HBV-specific CD8 + T cells. Autologous SLP-loaded and TLR- stimulated DC were used to activate patient HBc -specific CD8 + and CD4 + T cells.
Results
HBV-SLP was cross-submitted 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. Importantly, also patient-derived BDCA1 + mDC cross-presented and activated autologous T cell responses ex vivo.
Conclusions
As a proof of concept, we show 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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发表于 2017-12-8 08:30
