الفهرس 
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Abstract
Hepatitis C is prevalent worldwide, it is estimated that 130 170 million people, or 3% of the world’s population, are living with chronic hepatitis C . About 3 4 million people are infected per year.
Prevalence is higher in some countries in Africa and Asia.countries with particularly high rates of infection include Egypt (22%), Pakistan (4.8%) and China {3.2%} .
Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The long term hepatic impact of HCV infection is highly variable, from minimal changes to chronic hepatitis, extensive fibrosis , and cirrhosis with or without hepatocellular carcinoma.
Hepatitis C virus (HCV) is a small (55–65 nm in size enveloped, positive-sense single-stranded RNAvirus of the family Flaviviridae. Hepatitis C virus is the cause of hepatitis C in humans.
Hepatitis C virus particle consists of a core of genetic material (RNA), surrounded by an icosahedral protective shell of protein, and further encased in a lipid (fatty) envelope of cellular origin. Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope
Hepatitis C virus has a positive sense single-stranded RNAgenome. The genome consists of a single open reading frame that is 9600 nucleotide bases long..
The proteins of this virus are arranged along the genome in the following order: N terminal-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-C terminal.
HCV has 6 genotypes and several subtypes based on the variation in nucleotide sequence These genotypes have been further classified into subtypes (a,b,c,d, etc)
Difference among HCV genotypes in geographic distributions have provided investigators with an epiderniologic marker that can beused to trace the source of HCV infection in a given population .
Replication of HCV involves several steps. The virus replicates mainly in the hepatocytes of the liver, where it is estimated that daily each infected cell produces approximately fifty virions (virus particles) with a calculated total of one trillion virions generated. The virus may also replicate in peripheral blood mononuclear cells, potentially accounting for the high levels of immunological disorders found in chronically-infected HCV patients.
Hepatitic c virus has several methods of transmission ,like Intravenous drug use:, healthcare exposure sexual intercourse :Shared personal care items; vertical transimission.
Manifestation of Hepatitis C infection varies from acute symptoms which represent 15% of cases in the form of decreased appetite, fatigue, nausea, muscle or joint pains, and weight loss and infection resolves spontaneously in 10-50% of cases, to chronic infection which represent 80% of those exposed to the virus.Hepatitis C after many years becomes the primary cause of cirrhosis and liver cancer.
There are a number of diagnostic tests for hepatitis C including: HCV antibody enzyme immunoassay or ELISA, recombinant immunoblot assay, and quantitative HCV RNApolymerase chain reaction (PCR). HCV RNA can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and thus be detected.
Treatment is recommended in those with proven HCV infection liver abnormalities. Current treatment is a combination pegylated interferon alpha and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on HCV genotype. Improved outcomes are seen in 50–60% of people.
New pharmaceutical agents for treating hepatitis C currently in development include; new pharmaceutical formulations of IFN aimed at enhancing antiviral activity, RBV pro-drugs, protease inhibitors and polymerase inhibitors that are HCV-selective antiviral agents, and various others aimed at enhancing immune stimulatory activity .
One of medicine triumphs has been the control of many infectious diseases with prophylactic vaccines.Many virus infections could be controlled by appropriately designed vaccines , yet the existence of multiple serotypes sporadic nature , and economic realities may prevent this being achieved.
The need for a prophylactic HCV vaccine may be debated, since a change in social or cultural practices, such as the prevention of IVDU and the efficient screening of blood products and medical instruments worldwide would abort most new HCVinfections.
There are some groups that should be considered for vaccination are:Individuals with potential exposures to blood.;eg, military personnel, fire-fighters, policemen, emergency medical technicians.Patients with other causes of chronic liver disease Multiple sex partners .Births to HCV- infected mother . Sexual and household contacts of one or more infected individuals.
A key observation is that strong, broad adaptive immune responses are detected during acute infection and these persist in those who resolve infection - whereas persistent infection is associated with a weak, frequently undetectable HCV-specific T-cell response..and the HCV-specific T-cell response has been shown to play a crucial role in determining the outcome of primary HCV infection.
Over the last decade numerous HCV vaccine approaches have been assessed in mice and primates. Only a small fraction of animal HCV vaccine studies have progressed to human trials. The majority of these trials have evaluated potential therapeutic vaccines in HCV-infected patients. A smaller number have assessed vaccines in healthy volunteers; either with the aim of developing a prophylactic HCV vaccine or as a bridge to evaluating vaccine in HCV-infected patients.Four main vaccine strategies have been investigated in human clinical studies: recombinant protein vaccines, peptide vaccines, DNA vaccines and vector vaccines.:
Recombinant protein vaccines
The use of recombinant proteins as potential vaccine candidates assumes that inducing an immune response to a limited number of viral epitopes is sufficient to develop protective immunity.
Peptide vaccines
Like recombinant protein vaccines, peptide-based vaccines are well tolerated. They induce HCV-specific T-cell immunity through the direct presentation of vaccine peptide to the T-cell receptor via HLA molecules.
DNA vaccines
the first DNA vaccine was licensed for use to protect horses from West Nile virus .Initial work in the decade leading up to this significant accomplishment demonstrated that injection of a plasmid containing a gene could effectively result in protein expression in vivo and subsequently induce a host immune respons.Substantial research efforts have been aimed at developing an effective hepatitis C DNA vaccine
Vector vaccines
The use of viral vectors for the delivery of HCV RNA is an appealing vaccine choice. Adenoviral vectors have shown to be potent inducers of HCV-specific T-cell responses in the chimpanzee model and to reduce peak HCV viremia during primary infection.