Development of a novel Hsp70-based DNA vaccine as a multifunctional antigen delivery system.

DNA vaccination is a simple and effective method to induce immune responses against a variety of tumors as well as infectious diseases. Vaccination with major histocompatibility complex (MHC) class I tumor peptide has been carried out to induce an antigen-specific and tumor-reactive cytotoxic T lymphocytes (CTLs) response in vivo. In this study, we describe a novel DNA vaccine based on heat shock protein 70 (Hsp70), which can chaperon antigenic peptides and initiate innate and adaptive immune responses, to induce a more effective immune response. Ovalbumin (OVA) MHC class I epitope peptide (OVA(257-264): SIINFEKL) was selected as a model antigen and polyhistidine was used to facilitate the cytosolic delivery of the antigen-Hsp70 after endocytic uptake. A novel plasmid DNA vector encoding polyhistidine, Hsp70 and OVA(257-264) (pHis-Hsp70-pep) was designed. When mice were immunized with pHis-Hsp70-pep by intradermal injection in combination with electroporation, strong antigen-specific CTL responses were generated. pHis-Hsp70-pep also showed a significant protective effect against tumor challenge with an OVA-expression EL4 tumor line. These results indicate that the Hsp70-based DNA vaccine is useful as a multifunctional antigen delivery system to induce the antigen-specific immune response. (c) 2009 Elsevier B.V. All rights reserved.