TY - JOUR
T1 - Effects of antigen-expressing immunostimulatory liposomes on chemotaxis and maturation of dendritic cells in vitro and in human skin explants
AU - Lanzi, Anastasia
AU - Fehres, Cynthia M.
AU - De Gruijl, Tanja D.
AU - Van Kooyk, Yvette
AU - Mastrobattista, Enrico
PY - 2014/2/1
Y1 - 2014/2/1
N2 - Purpose: 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.
AB - Purpose: 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.
KW - cell-free protein synthesis
KW - chemotaxis
KW - DC activation
KW - DNA-vaccine
KW - liposome
UR - http://www.scopus.com/inward/record.url?scp=84896837498&partnerID=8YFLogxK
U2 - 10.1007/s11095-013-1179-0
DO - 10.1007/s11095-013-1179-0
M3 - Article
C2 - 24072262
AN - SCOPUS:84896837498
SN - 0724-8741
VL - 31
SP - 516
EP - 526
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 2
ER -
