Novel chitosan derivative nanoparticles enhance the immunogenicity of a DNA vaccine encoding hepatitis B virus core antigen in mice

✍ Scribed by Lei Jiang; Feng Qian; Xiaowen He; Fang Wang; Ding Ren; Ying He; Ka Li; Shuhan Sun; Chunhua Yin

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 752 KB
• Volume: 9
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1017

✦ Synopsis

Abstract

Background

Chitosan has been shown to possess useful properties such as non‐toxicity, high biocompatibility and non‐antigenicity that offer advantages for vaccine delivery systems. In this study, we prepared novel chitosan derivative nanoparticles as DNA vaccine carriers and the potential and mechanism of the DNA‐nanoparticle complexes in inducing augmented immune responses were explored.

Methods

The pVAX(HBc)DNA‐nanoparticle complexes as vaccine delivery systems were studied in several aspects: the protection against DNase I degradation was measured by an in vitro inhibition assay; the sustained expression of the plasmid in vivo was determined by RT‐PCR; the elevated uptake efficiency by phagocytes was observed with confocal microscopy; the biocompatibility was evaluated by cytotoxicity and histology assay; the complexes were administrated to C57BL/6 mice and the humoral and cellular immune responses were evaluated by ELISA, IFN‐γ production and cytolytic T lymphocyte (CTL)‐specific lysis assay.

Results

The remaining relative activity of DNase I after inhibition varied from 32.3% to 77.6%. The complexes were observed with higher uptake efficiency by phagocytes than naked DNA. Three types of nanoparticles did not induce significant cytotoxicity at concentrations ⩽400 µg/ml. No specific histological alteration related to the injection of the complexes was observed. The formulations of DNA‐nanoparticle complexes significantly enhanced the immunogenicity in several parameters: elevated antibody production, higher level of IFN‐γ secretion, and augmented specific cell lysis.

Conclusions

This study demonstrated the potential of the novel chitosan derivative nanoparticles for safe and effective DNA vaccine delivery. Copyright © 2007 John Wiley & Sons, Ltd.