Antitumor Immunity Induced by Genetic Immunization with Chitosan Nanoparticle Formulated Adjuvanted for HPV-16 E7 DNA Vaccine.

Abstract

In recent years attention has been paid to develop effective adjuvant systems for DNA vaccines. Co-formulation of a gene delivery vector with an immunostimulator can enhance therapeutic efficiency of DNA vaccine. To investigate the efficacy of chitosan as a nanodelivery system to enhance antitumor effects of human papilloma virus (HPV)-16 DNA vaccine with IL-12 gene for protection against TC-1 tumor using an animal model. The mice were challenged by subcutaneous injection of TC-1 cells and immunized intramuscularly with DNA vaccine thrice at seven-day intervals. One week after the last immunization, mice were sacrificed and antitumor effects were assessed through measuring lymphocyte proliferation, cytotoxicity, cytokines production, and tumor regression. We found that co-formulation and co-administration of chitosan nanoparticles and IL-12 with HPV-16 E7 DNA vaccine induced higher antitumor effects compared with chitosan or IL-12 alone. E7-specific lymphocyte proliferation index and CTL activity were found to be significantly higher in combination group in comparison to single vaccination with either chitosan or IL-12. Co-formulation of chitosan and IL-12 resulted in higher IFN-γ and IL-4, and decreased IL-10 production. Furthermore, combined vaccination highly inhibited the tumor progression compared with chitosan or IL-12 alone. Chitosan nanoparticle is a promising delivery system for DNA vaccine and IL-12 is an effective genetic adjuvant for the induction of strong antitumor immune response.