The journal of gene medicine · 2007
Novel chitosan derivative nanoparticles enhance the immunogenicity of a DNA vaccine encoding hepatitis B virus core antigen in mice.
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Jiang Lei, Qian Feng, He Xiaowen, Wang Fang, Ren Ding, He Ying, Li Ka, Sun Shuhan, Yin Chunhua
Аннотация
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-gamma 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<or=400 microg/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-gamma 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.
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-gamma 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<or=400 microg/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-gamma 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.