Protein direct delivery to dendritic cells using polymeric nanoparticles consisting of poly(γ-glutamic acid) derivatives for vaccination

POLY 328

Mitsuru Akashi, akashi@chem.eng.osaka-u.ac.jp, Center of Excellence (COE) Program for 21st Century, and Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan, Takami Akagi, akagit@chem.eng.osaka-u.ac.jp, Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan, Shinsaku Nakagawa, nakagawa@phs.osaka-u.ac.jp, Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 yamada-oka, Suita, Osaka, 565-0871, Japan, and Masanori Baba, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima-city, 890-8544, Japan.
Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Antigen-loaded polymeric nanoparticles have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. Here we show that a novel polymer-based nanoparticles that induce predominantly antigen-specific cytotoxic T lymphocyte (CTL) responses for protein-based vaccine delivery. We prepared antigen-loaded biodegradable nanoparticles composed of amphiphilic poly(γ-glutamic acid) (γ-PGA) derivatives (γ-hPGA). Proteins or peptides as an antigen were successfully immobilized on/into these nanoparticles. γ-hPGA nanoparticles efficiently taken up by dendritic cells (DCs), and enhances the maturation of DCs. Moreover, Antigen-encapsulated γ-hPGA nanoparticles is more potent priming CTL responses than antigen mixed complete Freund's adjuvant (CFA). These results suggest that antigen-loaded γ-hPGA nanoparticles provides an efficient vaccine delivery system for the induction of a CTL responses and the development of a viral and cancer vaccine.