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Study On Chimeric Genetic Immunization Of HBV And HCV

Posted on:2002-06-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:W YinFull Text:PDF
GTID:1104360032952498Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Hepatitis B and hepatitis C are major diseases in virus hepatitis. Both of them can be transmitted by transfusion, wound and nearly touch. Hepatitis B and hepatitis C include acute and chronic hepatitis. Over 200 thousand peoples cued of liver diseases every year and 70 percent of them was correlative with hepa~tis B and hepatitis C. Peoples can be infected by overlapped hepatitis B virus and hepatitis C virus. Anti-HCV is 20 to 30 percent in hepatocellar carcinoma(HCC) with HBsAg. In hepaocirrhosis, the rate of HCC with overlaping infection is much higher than that of non-B and non-C. HBV and HCV can interact and result in servious liver damage. The prognosis is worst than HBV or HCV infection. Though HBV vaccine has been used over the world, the protetion period of HBV infection is not enough long and the immune response is weak in some peoples. No vaccine has been used until now because of the high gene mutant in HCV. So it is important to contruct chimeric genetic vaccine of HBV and HCV. Genetic immunization (nucleic acid immunization) has emerged recently and has brought new hope for HBV and HCV infection. It is a promising novel strategy that naked DNA encoding spcific antigens and the regulatory elements are introduced directly into niamnialian tissue, and subsequently induce specific humoral and cellular immune responses to the expressed antigen. It抯 significantly cheaper to manufacture than recombinant polypeptide. The considerable costs involved in producing and purifying protein antigens would be avoided. It is found that only including virus core protein can induce antibody .6- after immunization but has no neutralization . So recently chimric HI3V envelope and HCV core gene contructs is generally used. HBV belongs to DNA virus known as hepadna viridae. The envelope open reading frame contains three in-phase translation start condons that divide the gene into three coding regions known as preS I, preS2 and 5, in which the major neutralizing antigen epitope locates. The commercially available hepatitis B vaccines presently used have mainly consisted of the S protein. It has shown that the B and T cell epitopes in preS 1 and preS2 are different from S antigen. It is not sure whether the preS 1 and preS2 antigens can improve protection of present vaccines. However, some researches suggest that they can enchance helper T cell to produce antibody. HCV belongs to single positive-strand RNA virus. Vaccine reearches has concentrated on HCV eore(C) protein and envelope(E) glycoproteins. The core gene shows greater sequence conservation among HCV strains and the core protein includes at least 5 epitopes of B and T cell. The immunogenicity of core protein is the strongest among the structural proteins and it is the most important target antigen for Cytotoxic T lyphocyte (CTL). So, the genetic immunization including C gene offers the potential advantage of inducing cellar immune responses. Morever, these cellar immune responses may also have the benefit of eradicating persistent viral infection from the host and help to overcome the low response to HCV protein vaccine because of the high mutant. On the basis of all these study, we contructed the chimeric genetic vaccine of HBV and HCV and investigated the humoral and cellular immune responses after genetic immunization. The stuidies consisted of: 1. Five recombinant eukaryotic expression plasmids were construc...
Keywords/Search Tags:Hepatitis B Virus Hepatitis C Virus, Chimeric Genetic Immunization, Humoral Immune Response, Cellular Immune Response
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