Approaches for the development of HBV vaccine and improvement the effectiveness of HBV vaccine

Hepatitis B virus (HBV) infection is a serious health problem all over the world. According to World Health Organization (WHO) one third of the world population have been infected with HBV and 370 million are chronic carriers of HBV. Despite the presence of the HBV vaccine and therapeutic drugs, about 1 million people die each year from HBV related diseases. Therefore, the more effective and cheaper alternative HBV vaccines are necessary.In this thesis, alternative vaccine studies were performed to overcome the immune tolerance especially in HBV carriers. In the first part of the study, the effect of recombinant phages expressing HBV surface antigens (HBsAg) on anti-HBsAg response was investigated in BALB/c, BALB/cj, HBV transgenic (HBV-tg) and hybrid (C57BL/6J×BALB/c) mice. In the second part of the study, commercial HBV vaccine was complexed with anti-HBsAg monoclonal antibody and its therapeutic effect was investigated in HBV-tg mice. In the last part, dendritic cell vaccine was used to overcome the immune tolerance in HBV-tg mice. For this aim, Dendritic cells were derived from bone marrow in vitro. The therapeutic effect of dendritic cells in the presence or absence of HBV vaccine, vaccine-antibody complex was investigated in HBV transgenic mice.Results have shown that, strong adjuvants should be used to induce immune response in HBV carriers and genetic background is effective on immune response. Our results also indicate that HBV vaccine should not be used for the stimulation of dendritic cells.