This program was initiated to elucidate a newly recognized modality of vaccination and to extend our long-term study of the immune response and clinical sequelae of hepatitis C virus (HCV) infection. One of the advantages of genetic immunization is that the endogenously expressed proteins can be recognized by class I MHC molecules and expressed on the cell surface. The MHC-antigen complex on the cell surface can be recognized by cytotoxic T lymphocytes (CTL), which in turn are activated and attack infected cells. The possibility of inducing an immune response to HCV core protein using DNA immunization provides an attractive alternative to classic vaccination. There are many problematic issues related to vaccine development for hepatitis C. One of the major concerns is the genetic stability of the infectious agent, HCV. There are two hypervariable regions in the putative HCV envelope proteins. Immune escape mutants observed were attributed to mutations in these regions. Experimentally infected chimpanzees and HCV patients were found to have repeated bouts of infection with either homologous or new strains of HCV. This-could also be one of the reasons that more than 80% of the infections become chronic. Directly inducing strong cell-mediated immunity, especially protective cytotoxic T lymphocyte, may not only help in preventing initial HCV infection, but may also produce immune modulation to overcome existing infection. During the past year, we have constructed several different plasmids containing HCV genes and were able to evaluate the induction of antibodies to HCV core proteins in mice. We are in the process of developing assays to measure CTL activity in the mouse model.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002076-02
Application #
6161493
Study Section
Special Emphasis Panel (DTM)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao et al. (2008) Induction of multispecific Th-1 type immune response against HCV in mice by protein immunization using CpG and Montanide ISA 720 as adjuvants. Vaccine 26:5527-34
Jin, Bo; Wang, Richard Y; Qiu, Qi et al. (2007) Induction of potent cellular immune response in mice by hepatitis C virus NS3 protein with double-stranded RNA. Immunology 122:15-27
Umemura, Takeji; Wang, Richard Y-H; Schechterly, Cathy et al. (2006) Quantitative analysis of anti-hepatitis C virus antibody-secreting B cells in patients with chronic hepatitis C. Hepatology 43:91-9
Sugauchi, Fuminaka; Wang, Richard Y-H; Qiu, Qi et al. (2006) Vigorous hepatitis C virus-specific CD4+ and CD8+ T cell responses induced by protein immunization in the presence of Montanide ISA720 plus synthetic oligodeoxynucleotides containing immunostimulatory cytosine-guanine dinucleotide motifs. J Infect Dis 193:563-72
Jiao, X; Wang, R Y-H; Feng, Z et al. (2004) DNA immunization encoding the secreted nonstructural protein 3 (NS3) of hepatitis C virus and enhancing the Th1 type immune response. J Viral Hepat 11:18-26
Jiao, Xuanmao; Wang, Richard Yan-Hui; Qiu, Qi et al. (2004) Enhanced hepatitis C virus NS3 specific Th1 immune responses induced by co-delivery of protein antigen and CpG with cationic liposomes. J Gen Virol 85:1545-53
Jiao, Xuanmao; Wang, Richard Y-H; Feng, Zhiming et al. (2003) Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization. Hepatology 37:452-60