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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.08.016

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]