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

Publication date: Available online 17 February 2020Source: Antiviral ResearchAuthor(s): Yingying Dou, Diahann T.S.L. Jansen, Aniek van den Bosch, Robert A. de Man, Nadine van Montfoort, Can Araman, Sander I. van Kasteren, Gijs G. Zom, Willem-Jan Krebber, Cornelis J.M. Melief, Andrea M. Woltman, Sonja I. BuschowAbstractSynthetic 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 dissociati...
Source: Antiviral Therapy - Category: Virology Source Type: research