Research On DNA Vaccine Of Hepatitis B

Nucleic acid vaccine is a new generation of vaccine beginning in the 90's, which has shows powerful potency in the prevention and therapy of many diseases. Because nucleic acid vaccine is a new kind of vaccine, there has been several issues unsolved. And among these issues, the security of nuclei acid is most important since it is related with the application of nucleic acid. We have done the research of toxicology as following in order to give the overall assessment of the security of HBV DNA vaccine.1. acute-term toxicity testThe acute toxicity of immune mice or guinea pig by intramuscular injection or hypodermic injection was evaluated according acute-term toxicity test. There was any obviously acute toxic reaction upon the HBV DNA vaccine immune mice or guinea pig. And half lethal dose was several hundred folds than the clinical dose.2. long-term toxicity test of repeated doseThe immune mice were divided into three groups according the intramuscular injection dose of HBV DNA vaccine (4.5mg/kg, 1.5mg/kg, 0.5mg/kg) in 56 days (the dosage is twice per week, then once per week). The toxicity was observed from the beginning of the test to post-discontinuation within 30 days. The result was demonstrated that there was no obvious alteration in body weigh, appetite and faeces of mice compared with control group. Clinical biochemical indicator and hematology indicator was fluctuated within normal limits. The toxic reaction related to HBV DNA vaccine didn't detect. Also the toxic revised didn't detect related to HBV DNA vaccine according autopsy and the test of organ weight. There wasn't the phenomena of immune tolerance in the immune mice, didn't detect antinuclear antibody, didn't induce the phenomena of immunopathogenesis such as chronic inflammation, nonspecific immune activation and so on. The chromosomal integration with plasmid was tested by PCR, and the result was confirmed that 20 copy plasmid confused into 1 μg genome DNA confuse could be detected, that is to say the probability that DNA integrated into the cytogene of host cell and let the host cell malignant transformation...