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

Journal of Controlled Release : Official Journal of the Controlled Release Society
Ayumi YamaokaYoshinobu Takakura

Abstract

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 d...Continue Reading

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Citations

Jun 3, 2011·Human Gene Therapy·Alice RochardPascal Bigey
Sep 21, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xianfeng ChenMark A F Kendall
Mar 20, 2012·Human Vaccines & Immunotherapeutics·Xin GuanYoshinobu Takakura
Jul 7, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Germain J P FernandoMark A F Kendall

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