期刊
ANTIVIRAL RESEARCH
卷 178, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2020.104746
关键词
Cross-presentation; Synthetic long peptide; TLR2-Ligand; Immunotherapy; Hepatitis B virus; Chronic HBV infection
资金
- NWO VIDI grant from the Dutch Research Council, the Netherlands [91712329]
- Dutch Ministry of Economic Affairs, the Netherlands (TKI-LSH) [LSHM16056]
Synthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core protein derived SLP was capable of boosting CD4(+ )and CD8(+) T cell responses in the presence of a TLR2-ligand in chronic HBV patients ex vivo. For optimal efficacy of a therapeutic vaccine in vivo, adjuvants can be conjugated to the SLP to ensure delivery of both the antigen and the co-stimulatory signal to the same antigen-presenting cell (APC). Dendritic cells (DCs) express the receptor for the adjuvant and are optimally equipped to efficiently process and present the SLP-contained epitopes to T cells. Here, we investigated TLR2-ligand conjugation of the prototype HBV-core SLP. Results indicated that TLR2-ligand conjugation reduced cross-presentation efficiency of the SLP-contained epitope by both monocyte-derived and naturally occurring DC subsets. Importantly, cross-presentation was improved after optimization of the conjugate by either shortening the SLP or by placing a valine-citrulline linker between the TLR2-ligand and the long SLP, to facilitate endosomal dissociation of SLP and TLR2-ligand after uptake. HBV-core SLP conjugates also triggered functional patient T cell responses ex vivo. These results provide an import step forward in the design of a therapeutic SLP-based vaccine to cure chronic HBV.
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