Safety and Immunogenicity of a Naked DNA-based Vaccine Therapy in Patients With Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study was to investigate whether HBV-DNA vaccination is safe and could
      restore immune responses in patients with chronic hepatitis B non responder to available
      therapies.
    

Detailed description: 
      -  Despite the availability of effective hepatitis B vaccines for many years, over 370
           million people remain persistently infected with hepatitis B virus (HBV). Persistent
           infection is associated with chronic liver disease that can lead to the development of
           cirrhosis and hepatocellular carcinoma in some patients. Viral persistence is thought to
           be related to poor HBV-specific immune responses.

        -  Interferon (IFN)-alpha treatment significantly decreases HBV replication in only one
           third of patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis
           B. Nucleoside analogues, such as lamivudine and adefovir dipivoxil, inhibit HBV
           replication and improve histological signs of liver disease,but their use is limited by
           the risk of relapse after treatment discontinuation and the emergence of drug-resistant
           viral variants.

        -  Patients with acute self-limited hepatitis B display detectable polyclonal and
           multispecific cytotoxic T lymphocyte and T helper (Th) responses to viral
           antigens,whereas these responses are weak or absent in chronic HBV carriers.

        -  Increasing the strength of HBV-specific T-cell responses to the levels found in patients
           recovering from infection is therefore a goal in the treatment of patients with chronic
           hepatitis.

        -  Immunization with a nucleic acid vaccine (DNA vaccine) usually elicits antibody
           responses and T lymphocytes with a Th1 cytokine profile. In animal models of chronic
           hepatitis B infection, including nonhuman primates, intramuscular injection of a plasmid
           encoding HBV envelope proteins induces rapid, strong, and sustained humoral and
           cell-mediated immune responses. Clinical trials of DNA vaccines for hepatitis B
           conducted in healthy adult volunteers using a plasmid encoding hepatitis B surface
           antigen and the gene gun as a delivery system showed good tolerance.

        -  We carried out a phase I trial of a HBV DNA vaccine in patients with chronic active
           viral hepatitis, aiming to restore HBV-specific immune responses and to assess safety
           regarding liver disease.
    

Intervention name(s): DNA vaccine
Intervention type(s): Biological
Intervention description(s): patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10
Other intervention name(s): pCMV-S2.S DNA
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatitis B; DNA vaccine; immunotherapy