Glycodendropeptides stimulate dendritic cell maturation and T cell proliferation: a potential influenza A virus immunotherapy

Mannosylation facilitates uptake and internalization of immunogenic peptides by antigen-processing cells expressing mannose receptors at their surface, such as DC-SIGN, a lectin that plays a key role in the immune response against different pathogens. This internalization, processing and subsequent MHC presentation may result in a strong T cell stimulation. Here, we hypothesized that combining mannose glycodendrons with multivalent presentation of peptide epitopes in a likewise dendron format would yield hybrid constructs, named glycodendropeptides (GDPs), with the capacity to enhance peptide immunogenicity, hence providing a novel and versatile platform for applications in immunotherapy. Thus, GDPs of different valencies displaying the NP366–374 epitope, a conserved sequence from the influenza A virus nucleoprotein (NP), have been built by two click chemistry-based methodologies and assessed as potential flu vaccine candidates. Preliminary evaluation of the ability of these constructs to stimulate dendritic cell maturation and lymphocyte proliferation was promising, showing the highest-functionalized NP366–374 GDPs as inducing the strongest immunostimulatory effect.This work was supported by the Instituto de Salud Carlos III (ISCIII) Thematic Networks and Co-operative Research Centres: RIRAAF (RD012/0013/0001 and RD012/0013/0016) and project ISCIII (PI12/02481); by Junta de Andalucía (CTS-7433) and the Nicolas Monardes Program (C-0044-2012 SAS 2013); and by Generalitat de Catalunya (SGR2009-00492) and Ministerio de Economía y Competitividad (MINECO), projects CTQ2011-23410 and SAF2011-24899. This work was co-financed by the European Regional Development Fund (ERDF