Effects of antigen-expressing immunostimulatory liposomes on chemotaxis and maturation of dendritic cells in vitro and in human skin explants.
OBJECTIVE
Antigen-Expressing Immunostimulatory Liposomes (AnExILs) represent a novel DNA vaccination platform based on the production of protein antigens from DNA templates inside liposomes mediated by an in vitro transcription and translation (IVTT) mix. The aim of this study was to analyze the effects of AnExILs on different dendritic cells (DCs) models and to better understand the role of the different components of this formulation on its adjuvanticity.


METHODS
The effect of β-galactosidase-expressing AnExILs on maturation and particle uptake by murine DC cell line, fresh human monocyte-derived DCs or human dermal DCs in skin explants was investigated and compared to the effects of either plain liposomes or IVTT mix alone.


RESULTS
AnExILs induced efficient DC chemotaxis and promoted up-regulation of maturation markers on murine DCs, due to the presence of IVTT in the formulation. Furthermore, the amount of active βGal associated with DCs was higher for AnExILs than for free βGal expressed in IVTT or βGal encapsulated into non-adjuvanted liposomes. Most interestingly, the same trend was observed with human DCs.


CONCLUSIONS
Both IVTT mix and liposomal vehicles were shown to be key components of the AnExIL formulation responsible for its adjuvanticity. AnExILs combine antigen production, adjuvanticity and delivery in one system, and can efficiently activate both murine and human DCs.
Department of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG, Utrecht, The Netherlands.
Anastasia
A
Lanzi
Cynthia M
CM
Fehres
Tanja D
TD
de Gruijl
Yvette
Y
van Kooyk
Enrico
E
Mastrobattista
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007114:Immunization; D008081:Liposomes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000941:Antigens; D008081:Liposomes; D001616:beta-Galactosidase