الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 100 |  |  |
| | | from | 100 | | |
Abstract
Hepatitis C virus is a worldwide problem and it is a major cause of both acute and chronic hepatitis. The World Health Organization (WHO)estimates about 3% of the world’s population has been infected with HCV and that there are more than 170 million chronic carriers who are at risk of developing liver cirrhosis and/or liver cancer.The existence of hepatitis C was postulated in the 1970s and proven in 1989 .br>Most strategies have focused on inducing T-cell responses to the NS HCV antigens, which are genetically conserved compared with the HCV envelope, and which are known to contain multiple CD4+ and CD8+ Tcell epitopes.Four main vaccine strategies have been investigated in human clinical studies: recombinant protein vaccines, peptide vaccines, DNA vaccines
and vector vaccines:-1-Recombinant protein vaccines
The principle of this approach is to isolate the gene(s) encoding the
appropriate protein and clone it in bacteria, yeast or mammalian cells.
While some recombinant proteins are sufficient in isolation to elicit a
strong immune response, others require adjuvant therapy, this include:
A-Envelope protein vaccines
the genetic variability of the HCV viral envelope, which is the main
target for anti-HCV antibodies, makes such an approach for a HCV
vaccine challenging. Nevertheless, recognition that the presence of preexisting
antibodies to HCV envelope proteins is associated with a betterresponse to PEG-IFN therapy and that anti-envelope antibodies can lead
to an attenuated course of primary infection , has led to therapeutic and
prophylactic vaccine studies, respectively, which aim to induce antienvelope
antibodies:
a.Prophylactic vaccine
The only published clinical trial of a prophylactic vaccine for HCV
utilized a recombinant E1/E2 heterodimer adjuvanted with adjuvant
MF59C ,Phase I study evaluated the vaccine in 60 healthy subjects. All
subjects developed neutralizing antibodies and T-cell lymphocyte
proliferation responses to E1/E2 and an inverse response to increasing
amounts of antigen was noted. The vaccine was well tolerated. The study
authors suggest that larger clinical trials to evaluate vaccine efficacy are
indicated .
b.Therapeutic vaccines
The first candidate therapeutic vaccine for HCV was administered to
humans in 2003 ,assessment of efficacy showed no change in HCV RNA
levels but, in some subjects, improvements in liver histology were seen; a
total of 24 HCV-infected patients underwent liver biopsies before and
after vaccination. In nine of these patients there was histological
improvement after 17 months. The observed increase in anti-E1 antibody
levels correlated with improvement in liver histological scores and
reduction in serum alanine transaminase levels .
B-Core proteins
In a Phase II, placebo-controlled trial, GI5005 was combined with
standard therapy (PEG-IFN/ ribavirin) in 66 chronic HCV-1 patients and