Polyanhydride particle vaccine platform enhances early antigen-specific cytotoxic T cell responses (P4366)

Abstract

Abstract Bioerodible nanoparticles have been shown to be useful as vaccine delivery vehicles. Previous work from this laboratory has shown that polyanhydride nanoparticles (NPs) can be used as an effective platform delivery system with the ability to modulate the release kinetics and to physicochemically stabilize protein antigens, activate dendritic cells, and elicit protective immunity to pathogens. The goal of this project was to evaluate the ability of the polyanhydride NPs to enhance cell-mediate immunity. Using a high frequency adoptive transfer model employing 3 x 106 OT I CD8+ T cells, we demonstrated significant expansion of ovalbumin (Ova)-specific CD8+ T cells that expressed an effector memory phenotype (CD44high CD62Llow) following immunization with Ova-loaded NPs. Induction of these effector CD8+ T cells resulted in the development of fewer and smaller tumors after implantation of EG7 tumor cells compared to mice immunized with Alum plus Ova or soluble Ova alone. To better model the naturally occurring low frequency of naïve CD8+ T cells, 3,000 OT I T cells were adoptively transferred prior to immunizing mice with one of three separate polyanhydride NP formulations (20:80 CPH:SA, 20:80 CPTEG:CPH, or 50:50 CPTEG:CPH). The results of these studies demonstrated that immunization with biocompatible and biodegradable 20:80 CPH:SA polyanhydride NPs effectively enhanced the induction of antigen-specific cytotoxic CD8+ T cells.