Induction of humoral and cellular immune responses by antigen-expressing immunostimulatory liposomes
Journal of Controlled Release , Volume 164 - Issue 3 p. 323- 330
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.
|Journal of Controlled Release|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Amidi, M, van Helden, M.J.G, Tabataei, N.R, de Goede, A.L, Schouten, M.J, de Bot, V, … Mastrobattista, E. (2012). Induction of humoral and cellular immune responses by antigen-expressing immunostimulatory liposomes. In Journal of Controlled Release (Vol. 164, pp. 323–330). doi:10.1016/j.jconrel.2012.08.016