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Induction of humoral and cellular immune responses by antigen-expressing immunostimulatory liposomes

Recently we have shown that liposomes can be used as artificial microbes for the production and delivery of DNA-encoded antigens. These so-called antigen-expressing immunostimulatory liposomes (AnExILs) were superior in inducing antigen-specific antibodies compared to conventional liposomal protein...

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Published in:Journal of controlled release 2012-12, Vol.164 (3), p.323-330
Main Authors: Amidi, Maryam, van Helden, Mary J.G., Tabataei, Neda Rafiei, de Goede, Anna L., Schouten, Marijn, de Bot, Volkert, Lanzi, Anastasia, Gruters, Rob A., Rimmelzwaan, Guus F., Sijts, Alice J.A.M., Mastrobattista, Enrico
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cited_by cdi_FETCH-LOGICAL-c452t-aa80db605136898d4c0ab94fc134abd49d74b56c9180c4bfee5ad9a20389c9e93
cites cdi_FETCH-LOGICAL-c452t-aa80db605136898d4c0ab94fc134abd49d74b56c9180c4bfee5ad9a20389c9e93
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container_title Journal of controlled release
container_volume 164
creator Amidi, Maryam
van Helden, Mary J.G.
Tabataei, Neda Rafiei
de Goede, Anna L.
Schouten, Marijn
de Bot, Volkert
Lanzi, Anastasia
Gruters, Rob A.
Rimmelzwaan, Guus F.
Sijts, Alice J.A.M.
Mastrobattista, Enrico
description Recently we have shown that liposomes can be used as artificial microbes for the production and delivery of DNA-encoded antigens. These so-called antigen-expressing immunostimulatory liposomes (AnExILs) were superior in inducing antigen-specific antibodies compared to conventional liposomal protein or DNA vaccines when tested in mice after i.m. immunization. In this study, we investigated the capacity of AnExILs to induce T-cell responses. By using a plasmid vector encoding a model antigen under control of both the prokaryotic T7 and the eukaryotic CMV promoter we hypothesized that antigen production could lead to CTL activation via two distinct routes: i. production of antigens inside the AnExILs with subsequent cross-presentation after processing by APCs and ii. endogenous production of antigens after AnExIL-mediated transfection of the pDNA. Although we were not able to demonstrate transfection-mediated expression of luc-NP in mice, i.m. injection of AnExILs producing luc-NP resulted in T-cell responses against the encoded NP epitope, as determined by tetramer staining. T-cell responses were comparable to the responses obtained after i.m. injection of naked pDNA. In order to find out whether CTL activation was caused by cross-presentation of the exogenous antigens produced inside AnExILs or by endogenous antigen production from transfection with the same pDNA source a second study was initiated in which the contribution of each of these effects could be separately determined. These results demonstrate that the observed T-cell responses were not exclusively caused by cross-presentation of the AnExIL-produced antigens alone, but were rather a combination of dose-dependent antigen cross-presentation and low levels of endogenous antigen production. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2012.08.016
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ispartof Journal of controlled release, 2012-12, Vol.164 (3), p.323-330
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subjects Adjuvants, Immunologic - administration & dosage
Animals
antibodies
Antigens - genetics
Antigens - immunology
beta-Galactosidase - genetics
beta-Galactosidase - immunology
Biological and medical sciences
Cell-free protein synthesis
Cell-mediated immunity
Cytomegalovirus
DNA vaccines
dose response
epitopes
Female
General pharmacology
Immunity, Cellular - immunology
Immunity, Humoral - immunology
immunization
Liposomes
Luciferases - genetics
Luciferases - immunology
Lymphocyte Activation - immunology
Medical sciences
Mice
Mice, Inbred C57BL
microorganisms
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
plasmid vectors
Plasmids
recombinant vaccines
T-lymphocytes
T-Lymphocytes - immunology
transfection
Vaccines, DNA - administration & dosage
Vaccines, DNA - immunology
title Induction of humoral and cellular immune responses by antigen-expressing immunostimulatory liposomes
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