Potentiating Antigen Specific Immune Response by Targeted Delivery of the PLGA-Based Model Cancer Vaccine

Targeted delivery of vaccine has the potential to localize the therapeutic agent to a target tissue with minimum side-effects. This article presents the development of a model targeted immunotherapeutic approach that will harness effective T cell response. Here, we investigated the impact of a model nanoparticulate cancer vaccine on the immune system of in vivo mice models. The nanoparticles (NPs) were prepared by a double emulsification solvent evaporation technique. The anti-CD205 targeted formulations were obtained either through physical adsorption or a covalent conjugation method. The structural integrity of ovalbumin (OV) was confirmed by circular dichroism spectroscopy. Flow cytometry and enzyme-linked immunosorbent assay experiments were performed to evaluate T cell proliferation and cytokine secretion. Our results indicate that the antigen-adjuvant combined formulation induced more powerful responses compared to formulations with either of these alone. Wild-type balb/c mice immunized with the targeted poly (D,L-lactic- co-glycolic-acid) (PLGA) NPs encapsulated with OV and monophosphoryl lipid A (MP) induced profound secretion of antigen-specific IgG antibodies and cytokines and generation of memory T cells. OV specific T cell receptor transgenic OT1 mice showed the highest production of cytotoxic T cells and increased the secretion of cytokines upon immunization with the targeted OVMP formulations. The enhanced response might be attributed to the OV depot effect at the subcutaneous site of injection that triggered effective induction of dendritic cells activation and helper T cell differentiation in the lymph nodes. Therefore, the developed targeted PLGA-based delivery system could be utilized as a successful model vaccine in the future.