| Deoxyribonucleic acid vaccine (DNA vaccine), which is also named nucleic acid vaccine or gene vaccine, is a novel vaccine developing with gene therapy technology in recent years. Compared to normal vaccine, DNA vaccine have DNA vaccine not only has advantages of live attenuated vaccine, but also has safety of inactivated vaccine or subunit vaccine, and has both preventive effection and therapeutic effection. Therefore, DNA vaccine for therapy is the key point of research in recent years, and rapidly expands from the treatment of communicable disease to the treatment of the non-communicable disease. Recently, DNA vaccines have entered into a variety of human clinical trials for vaccines against various infectious diseases and for therapies against cancer. Despite their rapid and widespread development, however, however, the disappointing potency of the DNA vaccines in humans underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. In order to improve the efficacy of DNA vaccines, a lot of novel strategies have been performed. The definition of molecular mechanism of DNA vaccine must lead to gain more effective DNA vaccine approaches. However, the mechanisms of immune responses for DNA vaccines are still not entirely understood. In order to improve understanding of the immune response mechanisms.How to improved the immunity of DNA vaccine and illuminated the mechanism of DNA vaccine have an essential sense for the development of DNA vaccine.Nowadays, more and more immune methods and immune dosage offers a promising alternative to DNA vaccine, in this article, we apply the approach micro-needles inoculation and Flt3L at the same time to improved the immune response of HBV DNA vaccine. Micro-needles advance in micro-electrical mechanical systems, containing micro-fabricated polymer projections, mechanically disrupts the skin barrier and delivers vaccines to the epidermis. Since, the projections of micro-needles range from 50 to 200 um can penetrate the skin surface and into the epidermis, where DNA are readily taken up by affluence APCs, leading to powerful antigen presentation in regional inductive immune sites. Flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration, also some report suggest that the use of Flt3L can activate DCs. We assess the immunization effects of several immune strategies in C57BL/6 mice. DNA vaccine adjuvant with plasmid pFlt3L inoculated by micro-needles induced significant stronger humoral and cellular immune responses than other immune strategies.The safety problems effect the development of DNA vaccine for a long time, in recent year, some research found used DNA vaccine induced autoimmunity in animal kidney, researcher found the kidney disease after dissect the autoimmune animal, the mechanism was been found, the deposit of antigen antibody complex in kidney induce the autoimmunity response. In addition, in journal nature, some research reported the adjuvant CpG induce the liver pathological changes in experimental animal. To clarity the mechanism of this unsafely phenomenon, We constructed the Annexin-B1-expressing plasmid pVAX-B1 and pcDNA3-B1, and then we immunized C57BL/6 mice with pVAX-B1, pcDNA3-B1 and AnnexinB1, The humoral and cellular immune responses at different time point were evaluated by ELISA assay, ELISPOT and CTL specific lysis assay. We found in group pcDNA3-B1 mice develop vitiligo but not in pVAX-B1-vaccinated mice, In order to explain the Furthermore, we compared different group diversity by proteomics. In comparison with proteome of pVAX-B1-vaccinated mice,2 proteins in group pcDNA3-B1 were up-regulated and 3 proteins down-regulated by more than 2.5-fold in quantity, growth factor receptor bound protein 2 hold definite association with immune responses; proxiredoxin 1 and proxiredoxin 6 association with security of DNA vaccine, the proxiredoxin 1 and proxiredoxin 6 were member of anti-oxidative family, the function of the family is to prevent the development of oxidative stress,do some research we found the down-regulation of proxiredoxin 6 evocate the generate of oxidative stress then induced the develop of autoimmune disease. So the proxiredoxin 6 might be potential markers of successful vaccination and provide research targets for molecular mechanism of vaccinology... |
