Anti HBV Specific Active Immunotherapy

(Anti HBV Therapeutic Vaccine)

Anti HBV Specific Active Immunotherapy (Anti HBV Therapeutic Vaccine) using recombinant hepatitis B vaccine (standard HBV vaccine) as an immunogenic specific antigen and several cytokines as an immune adjuvant is a new antiviral approach for chronic HBV infection. The first and most critical setp in the design of an anti HBV therapeutic vaccine is the selection of the specific antigens that will be used to construct the vaccine. These antigens must be able to stimulate strong and clinically effective anti HBV immune responses in patients with chronic HBV infection. The second important setp in the design of anti HBV therapeutic vaccine is the selection of the adjuvants. These adjuvatns when administered locally with HBV specific antigen are capable of endowing the host with a previously nonexistent immune response or heightening an existing one. Recently, animal experimental studies and clinical investigations indicated that recombinant hepatitis B virus S protein and an adjuvant constructed by several cytokines in an optimal proportion can be used for design of anti HBV therapeutic vaccine. For this reason, our anti HBV therapeutic vaccine is constructed by recombinant hepatitis B vaccine (as a specific antigen) and several cytokines in an optimal proportion (as an adjuvant).

The action of this anti HBV therapeutic vaccine is to induce a complex antiviral response within the liver. This complex antiviral response is initiated by HBV antigen specific cytotoxic T lymphocytes (CTL). So, when the therapeutic vaccine is administered locally, CTLs can be activated by the vaccine, and this activated CTLs iniciate a complex antiviral response in the liver, and resulted in viral clearance. This viral clearance is attributable primarily to the effects of inflammatory cytokines, especially interferon gamma (IFN-g) and tumor necrosis factor alpha (TNF-a), that are released by the CTLs when they recognize their viral target antigen on the hepatocytes. These cytokines activate the liver NK and NKT cells to produce additional IFN-g, which activate the hepatocytes to an antiviral state that is destructive for the virus while being compatible with survival of the liver cells.

Most patients with chronic HBV infection develop immunological tolerance, they didn’t have any CTL response. In this condition the action of anti HBV therapeutic vaccine is to break the immune tolerance and to reconstruct the CTLs response, eventually to activate the complex antiviral responses.

The therapeutic vaccine can be used as a specific immunological treatment for chronic HBV infection, including chronic hepatitis B and chronic HBV carrier. Recent clinical studies revealed that the anti HBV therapeutic vaccine combined with antiviral drugs including interferon-a and lamivudine showed an effective result in the clearance of hepatitis B virus.

 

       

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