Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically increases uptake and maturation by dendritic cells while minimizing the adjuvant dosage

被引：14

作者：

Fichter, Michael ^{[1
]}

Dedters, Marvin ^{[1
]}

Pietrzak-Nguyen, Anette ^{[1
]}

Pretsch, Leah ^{[1
]}

Meyer, Claudius U. ^{[1
]}

Strand, Susanne ^{[2
]}

Zepp, Fred ^{[1
]}

Baier, Grit ^{[3
]}

Landfester, Katharina ^{[3
]}

Gehring, Stephan ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Childrens Hosp, Univ Med Ctr, D-55131 Mainz, Germany

[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 1, D-55131 Mainz, Germany

[3] Max Planck Inst Polymer Res, D-55128 Mainz, Germany

来源：

VACCINE | 2015年 / 33卷 / 07期

关键词：

Nanocapsules; Dendritic cell targeting; Hydroxyethyl starch; Vaccine; Monophosphoryl lipid A; TLR4; C VIRUS-INFECTION; SCAVENGER RECEPTORS; VACCINE DEVELOPMENT; TARGETED DELIVERY; IMMUNE-RESPONSES; VIRAL CLEARANCE; INNATE IMMUNITY; ANTIGEN; PARTICLES; IMMUNOTHERAPY;

D O I：

10.1016/j.vaccine.2014.12.072

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-gamma (IFN-gamma) and/or monophosphoiyl 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 T(h)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 T(h)1-prone cellular immune response. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：838 / 846

页数：9

共 48 条

[1] Adjuvants for human vaccines [J].

Alving, Carl R. ;

Peachman, Kristina K. ;

Rao, Mangala ;

Reed, Steven G. .

CURRENT OPINION IN IMMUNOLOGY, 2012, 24 (03) :310-315

[2] A hepatitis B vaccine formulated with a novel adjuvant system [J].

Ambrosch, F ;

Wiedermann, G ;

Kundi, M ;

Leroux-Roels, G ;

Desombere, I ;

Garcon, N ;

Thiriart, C ;

Slaoui, M ;

Thoelen, S .

VACCINE, 2000, 18 (20) :2095-2101

[3] Pivotal Advance: Toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis [J].

Amiel, Eyal ;

Alonso, Anselmo ;

Uematsu, Satoshi ;

Akira, Shizuo ;

Poynter, Matthew E. ;

Berwin, Brent .

JOURNAL OF LEUKOCYTE BIOLOGY, 2009, 85 (04) :595-605

[4] Enhanced in Vivo Targeting of Murine Nonparenchymal Liver Cells with Monophosphoryl Lipid A Functionalized Microcapsules [J].

Anette Pietrzak-Nguyen ;

Fichter, Michael ;

Dedters, Marvin ;

Pretsch, Leah ;

Gregory, Stephen H. ;

Meyer, Claudius ;

Doganci, Aysefa ;

Diken, Mustafa ;

Landfester, Katharina ;

Baier, Grit ;

Gehring, Stephan .

BIOMACROMOLECULES, 2014, 15 (07) :2378-2388

[5] Suppressing Unspecific Cell Uptake for Targeted Delivery Using Hydroxyethyl Starch Nanocapsules [J].

Baier, Grit ;

Baumann, Daniela ;

Siebert, Joerg Max ;

Musyanovych, Anna ;

Mailaender, Volker ;

Landfester, Katharina .

BIOMACROMOLECULES, 2012, 13 (09) :2704-2715

[6] Regulation of phagosome maturation by signals from Toll-like receptors [J].

Blander, JM ;

Medzhitov, R .

SCIENCE, 2004, 304 (5673) :1014-1018

[7] In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination [J].

Bonifaz, LC ;

Bonnyay, DP ;

Charalambous, A ;

Darguste, DI ;

Fujii, SI ;

Soares, H ;

Brimnes, MK ;

Moltedo, B ;

Moran, TM ;

Steinman, RM .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (06) :815-824

[8] Vaccine delivery carriers: Insights and future perspectives [J].

Correia-Pinto, J. F. ;

Csaba, N. ;

Alonso, M. J. .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2013, 440 (01) :27-38

[9] TARGETING NANOPARTICLES TO DENDRITIC CELLS FOR IMMUNOTHERAPY [J].

Cruz, Luis J. ;

Tacken, Paul J. ;

Rueda, Felix ;

Carles Domingo, Joan ;

Albericio, Fernando ;

Figdor, Carl G. .

NANOMEDICINE: INFECTIOUS DISEASES, IMMUNOTHERAPY, DIAGNOSTICS, ANTIFIBROTICS, TOXICOLOGY AND GENE MEDICINE, 2012, 509 :143-163

[10] Particulate vaccines: on the quest for optimal delivery and immune response [J].

De Temmerman, Marie-Luce ;

Rejman, Joanna ;

Demeester, Jo ;

Irvine, Darrell J. ;

Gander, Bruno ;

De Smedt, Stefaan C. .

DRUG DISCOVERY TODAY, 2011, 16 (13-14) :569-582

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