Design of TLR2-ligand-synthetic long peptide conjugates for therapeutic vaccination of chronic HBV patients.

Design of TLR2-ligand-synthetic long peptide conjugates for therapeutic vaccination of chronic HBV patients. Antiviral Res. 2020 Feb 17;:104746 Authors: Dou Y, Jansen DTSL, van den Bosch A, de Man RA, van Montfoort N, Araman C, van Kasteren SI, Zom GG, Krebber WJ, Melief CJM, Woltman AM, Buschow SI Abstract 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...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research