Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically increases uptake and maturation by dendritic cells while minimizing the adjuvant dosage. Issue 7 (11th February 2015)

• Record Type: Journal Article
• Authors: Fichter, Michael; Dedters, Marvin; Pietrzak-Nguyen, Anette; Pretsch, Leah; Meyer, Claudius U.; Strand, Susanne; Zepp, Fred; Baier, Grit; Landfester, Katharina; Gehring, Stephan
• Is Part Of: Vaccine. Volume 33:Issue 7(2015)
• Page Start: 838
• Page End: 846
• Publication Date: 2015-02-11
• Subjects: Nanocapsules -- Dendritic cell targeting -- Hydroxyethyl starch -- Vaccine -- Monophosphoryl lipid A -- TLR4; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2014.12.072
• Languages: English
• ISSNs: 0264-410X

Abstract

Graphical abstract: Highlights: Coating with the vaccine adjuvant MPLA onto hydroxyethyl starch nanocapsules promoted phagocytosis by human monocyte-derived dendritic cells and led to phenotypic maturation and the induction of IL-12 secretion as an indicator for a Th1-directed response. The applied dose of MPLA for the activation of moDCs could be reduced by immobilization onto the capsule surface indicating a dose reduction potential. Abstract: Enhancing delivery of antigens to dendritic cells (DCs) is essential for the induction of vigorous antigen-specific cellular immune responses. Aim of the present study was to evaluate the properties of hydroxyethyl starch nanocapsules (HES-NCs) functionalized with anti-CD40, anti-DEC205, interferon-γ (IFNγ) and/or monophosphoryl lipid A (MPLA) with respect to the overall uptake, the released cytokine profile, and the influence on phenotypic maturation of human monocyte-derived DCs using flow cytometry, confocal microscopy and enzyme-linked immunosorbent assays. NC uptake by DCs was significantly enhanced by functionalizing NCs with anti-CD40 or MPLA. With respect to the cytokine profile and the maturation status, coating with MPLA evoked a strong Th 1-type cytokine response and significantly increased CD80 and CD83 expression on DCs, contrasting the moderate effects of MPLA in solution. Notably, an at least 20 fold higher amount of MPLA in solution was needed compared to the dosage of MPLA attached to HES-NCs in order to induce comparable effects, evidencing the intense dose-sparing potential of particle-bound MPLA. Reducing the amount of the vaccine adjuvant MPLA, while maintaining or even surpassing the effects on human DCs, reveals the potential of HES-NCs as a promising carrier system for the simultaneous delivery of antigen along with compounds promoting a Th 1-prone cellular immune response.