Study On Multi-organ Injuries And Its Mechanism Induced By HBV DNA-mediated Immunization

The hepatitis B virus (HBV) is an enveloped DNAthat causes acute and chronic liver disease characterized by a necroinflammatory lympho-mono nuclear cell infiltrate and Kupffer cell hyperplasia. HBV infection in immuno -comentent adults usually results in a self-limited, transient liver disease and viral clearance. A small proportion of these patients (5%~10%) develop chronic hepatitis associated with viral persistence. When neonates are infected, however, over 90% of them will become persistently infected, suffering different degrees of chronic liver disease. A quarter to one-third of those who infected chronically with HBV will develop progressive liver diseases (including cirrhosis and primary liver cancer).DNA-mediated immunization refers to the induction of an immune response to antigen expressed in vivo subsequent to the introduction of DNA carrying the protein coding sequences and the necessary regulatory elements needed to express them. The protein processed by antigen presentation cell (APC) can stimulate the immune system to produce the protective immune response including specific CTL response and specific antibody production. Activation of immune response to HBV by vaccination is thought to be the most effective means to prevent HBV infection. In addition to conventional vaccination, DNA-mediated immunization has been developed as an alternative approach for prevention and therapy of different infectious diseases, including HBV infection.The mechanism of chronic HBV infection is mainly related to the multi-specific CTL responses, which cannot kill and eliminate HBV effectively. The CTL response is absent or extremely weak in chronically infected patientsalthough there has some HBV antigen specific T lymphocytes in these patients. The immune response to hepatitis B surface antigen (HBsAg) can be efficiently evoked by DNA-mediated immunization compared to subunit recombinant vaccine. The expression of HBV DNA in transgenic mice can be inhibited by HBV DNA vaccine when inoculated it. This suggests that DNA-mediated immunization has the potential therapeutic effect on chronic HBV infection.Although it has been demonstrated that the HBsAg gene can be continually expressed for a long time in the injected muscle tissue and the HBsAg protein in the sera of immunized mice can be continuously detected for more than 2 months, its effectiveness inducing immune response to HBV and the side effects associated with DNA-mediated HBV immunization remain poorly understood. In order to study the possibility of DNA-mediated vaccination for prevention and therapy of HBV and the pathological basis of side effects associated with DNA-mediated immunization, the pcDNAS2-S constructor was made containing recombinant HBsAg gene and the BALB/c mice were treated by muscular injection. The humoral immune response and systemic pathological injuries were evaluated in mice treated by muscular injection of constructor containing recombinant HBsAg gene.The experimental approaches for studying HBV pathogenesis is difficult because the host range of HBV is limited to human and chimpanzees, and also because in vitro system for the propagation of HBV was not established. Transgenic animal technology was applied in1980s. With the development of transgenic technology, there are more than a hundred kinds of transgenic animal models for human diseases have been established, especially in tumor, infectious disease and genetic disease. In 1985, the first transgenic mouse carrying HBV genes was generated, and thereafter the transgenic mouse system was applied in HBV studies. It's the ideal animal model for researching the replication and pathogenesis of HBV, exploring the mechanism of liver carcinoma induced by HBV and so on. At the present study, the transgenic mice were adopted the anti-sera and induced the multi-organ injury on the basis of analysis of the expression characteristic of transgenic mice so as to discuss the possibility of this model on the pathogenesis and therapy of chronic liver disease.In this study, HBsAg preS2-S exp...