Hallengärd David, Bråve Andreas, Isaguliants Maria, Blomberg Pontus, Enger Jenny, Stout Richard, King Alan, Wahren Britta
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Nobels väg 16, 171 77, Stockholm, Sweden.
Genet Vaccines Ther. 2012 Aug 8;10(1):5. doi: 10.1186/1479-0556-10-5.
The use of optimized delivery devices has been shown to enhance the potency of DNA vaccines. However, further optimization of DNA vaccine delivery is needed for this vaccine modality to ultimately be efficacious in humans.
Herein we evaluated antigen expression and immunogenicity after intradermal delivery of different doses of DNA vaccines by needle or by the Biojector jet-injection device, with or without the addition of electroporation (EP).
Neither needle injection augmented by EP nor Biojector alone could induce higher magnitudes of immune responses after immunizations with a high dose of DNA. After division of a defined DNA dose into multiple skin sites, the humoral response was particularly enhanced by Biojector while cellular responses were particularly enhanced by EP. Furthermore, a close correlation between in vivo antigen expression and cell-mediated as well as humoral immune responses was observed.
These results show that two optimized DNA vaccine delivery devices can act together to overcome dose restrictions of plasmid DNA vaccines.
已证明使用优化的递送装置可增强DNA疫苗的效力。然而,为使这种疫苗形式最终在人类中有效,还需要进一步优化DNA疫苗的递送。
在此,我们评估了通过针头或Biojector喷射注射装置皮内递送不同剂量DNA疫苗后,添加或不添加电穿孔(EP)时的抗原表达和免疫原性。
用高剂量DNA免疫后,无论是通过EP增强的针头注射还是单独的Biojector都不能诱导更高强度的免疫反应。将确定剂量的DNA分散到多个皮肤部位后,Biojector特别增强了体液反应,而EP特别增强了细胞反应。此外,观察到体内抗原表达与细胞介导的以及体液免疫反应之间密切相关。
这些结果表明,两种优化的DNA疫苗递送装置可以共同作用以克服质粒DNA疫苗的剂量限制。