Abstract：To provoke an immune response against HBsAg in chronic HBV infections for interrupting the infection processes has been the purpose of therapeutic HBV vaccine. The vaccines research is basically the biological agents with the immunogenicity of HBV HBsAg. Due to the DNA sequence, the molecular structure and immunogenicity of HBsAg in HBV have no connection with those of HBV HbeAg at all; the HBeAg is a free and non-membrane antigen, therefore the anti-HBeAg response has no effect on the immune clearance reactions of HBV and infected hepatocytes in chronic HBV infections. Up to now, only with the clinical data about HBeAg system in serum with patients studied in Phase II clinical investigation, the treatment effectiveness of therapeutic HBV vaccine is still unable to be determined. The applications of vaccines is prophylactic in the sense of preventing viruses or bacteria from invasion, however the effort of therapeutic vaccines is that develops immune responses against persistent viral infections in an immune tolerant situation after exposure. It still remains a vision without the support from scientific rationale. Under the conditions of liver cells widespread infected by HBV in chronic HBV infection, while the anti-HBsAg response had been provoked with the treatment of therapeutic vaccine in these individuals, the free virus and HBsAg antigen particles in serum might be cleared, even the infected liver cells should be directly attacked as with accompanying circumstances, the degree of liver damage associated with the immune pathology as well as a corresponding risk could not possible estimate because of the infected degree of liver cells is hard to be estimated before chronic HBV infection treatment. Since the applications implicate such a risk, it is one of the important factors for the therapeutic HBV vaccine that is unable to get out of the laboratory. The future of therapeutic HBV vaccine seems doomed unless new and applicable immunologic principles are discovered.