Clinical study on safety and immunogenicity of therapeutic dual-plasmid HBV DNA vaccine mediated by in vivo electroporation

Objective　 To evaluate the safety and immunogenicity of the therapeutic dual-plasmid HBV DNA vaccine mediated by electroporation (EP) in vivo against the hepatitis B virus in healthy adult volunteers. Methods　The enrolled 30 healthy volunteers were randomly divided into three dosage groups (10 volunteers in each group), namely: high-dose (4mg), middle-dose (2mg) and low-dose (1mg) groups. Volunteers received four intramuscular injections of HBV DNA vaccine mediated by in vivo EP at the 0, 4th, 12th and 24th week. Each dose group was further divided into 2 sub-groups (5 persons/per group) with different EP frequencies, i.e. 36 and 60 volt. The changes in response was determined by physical diagnosis (ECG, chest X-ray, type-B ultrasound), lab findings (blood and urine routine, blood biochemistry, prothrombin time, thyroid function, tumor biomarkers), immunological variables (IFN-γ, ANA, anti-dsDNA Ab), serological variables pertaining to HBV (HBsAg, HBcAb, HBeAg, HBeAb, HBV DNA) and serum anti-HBs status in volunteers before and after receiving EP mediated HBV DNA vaccination. Results　The dual-plasmid HBV DNA vaccination mediated by in vivo EP was well tolerated in all healthy volunteers with a stable life signs. It was found that EP-mediated immunization of the therapeutic DNA vaccine against hepatitis B virus had a specific and obvious anti-HBs humoral immune response in one volunteer (17.22mU/ml). Four repeated intramuscular injections of the vaccine did not show any significant adverse effects in the receptors. Although mild elevation of serum ALT and enlarged spleen were found in one individual, the abnormalities disappeared spontaneously at the end of the trial. Conclusions　EP-mediated dual-plasmid HBV DNA vaccine is safe and well tolerated with certain degree of humoral immunogenicity.