Immunotherapy for HCV infection: next steps

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6100, USA.
Expert Review of Vaccines (Impact Factor: 4.21). 10/2008; 7(7):915-23. DOI: 10.1586/14760584.7.7.915
Source: PubMed


With more than 170 million individuals currently infected, HCV is a global pandemic, effecting approximately 3% of the entire world's population. HCV infection is a growing infectious disease pandemic with approximately 3-4 million new cases reported each year. Due to the persistent nature of the virus, 70-90% of infected individuals will develop chronic infection, which can lead to progressive liver disease including cirrhosis and hepatocellular carcinoma. Current standard treatment with a combination of IFN-alpha and ribavirin has improved the prognosis for many HCV sufferers; however, infection is very difficult to treat successfully and the protocol for treatment is neither simple, well tolerated nor economically favorable. Standard treatment can cost an average of US$22,000, and depending on genotype, as few as 42% of treated individuals will clear the infection. This collection of treatment issues combined with new concepts in immune therapy serve to underscore an urgent need for the development of improved immunotherapies, such as novel interferons, and support the possible development of therapeutic vaccines for the treatment of chronic HCV infection.

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    • "The incidence of Hepatitis C virus (HCV) infection has been steadily increasing in the last few decades in China and is expected to intensify in the coming years worldwide 1. Peptide-based vaccines have been generated and tested in pre-clinical and clinical trials 2. However, the development of effective peptide-based vaccines has been significantly hampered by the high genetic variability of HCV. "
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    ABSTRACT: Hepatitis C virus (HCV) heterogeneity accounts for the failure of effective vaccine development and the lack of successful anti-viral therapy in some patients. Little is known about the immune response to HCV peptides and the region or race specific genotypes in China. The objective of this study was to characterize HCV antibody immune response to HCV peptides and HCV genotypes in different regions and races of China. A total of 363 serum samples were collected from HCV carriers in 6 regions in China. The immune response to HCV peptides was evaluated by ELISA. HCV genotypes were examined using nested RT-PCR. We found that the anti-HCV antibody neutralization rates were significantly different among the serum samples from different areas or from different races in the same area. For samples from Tibet and Sinkiang, the rates of neutralization by HCV peptides were only 3.2% and 30.8%, respectively. The genotypes of samples from Tibet and Sinkiang were apparently heterogeneic and included type I, II, III and multiple types (I/II/III, I/II, I/III, II/III). One specific sample with multiple-genotype (I/II/III) HCV infection was found to consist of type I, II, III, II/III and an unclassified genotype. These studies indicate that the anti-HCV antibody immune response to HCV peptides varied across regions and among races. The distribution of HCV genotypes among Tibetans in Tibet and Uighurs in Sinkiang was different from that in the inner areas of China. In addition, a "master" genotype, type II, was found to exist in HCV infection with multiple HCV genotypes.
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    ABSTRACT: We have focused our research on understanding the basic biology of and developing novel therapeutic and prophylactic DNA vaccines. We have among others three distinct primary areas of interest which include: 1. Enhancing in vivo delivery and transfection of DNA vaccine vectors 2. Improving DNA vaccine construct immunogenicity 3. Using molecular adjuvants to modulate and skew immune responses. Key to the immunogenicity of DNA vaccines is the presentation of expressed antigen to antigen-presenting cells. To improve expression and presentation of antigen, we have investigated various immunization methods with current focus on a combination of intramuscular injection and electroporation. To improve our vaccine constructs, we also employed methods such as RNA/codon optimization and antigen consensus to enhance expression and cellular/humoral cross-reactivity, respectively. Our lab also researches the potential of various molecular adjuvants to skew Th1/Th2 responses, enhance cellular/humoral responses, and improve protection in various animal models. Through improving our understanding of basic immunology as it is related to DNA vaccine technology, our goal is to develop the technology to the point of utility for human and animal health.
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