Abstract
Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.
Highlights
Hepatitis C Virus (HCV) is a global health problem that affects almost 3% of the world’s population [1] and not less than 15% of the Egyptian population [2]
Individuals with chronic HCV infection usually remain asymptomatic and undiagnosed for decades before chronic hepatitis leads to severe fibrosis and cirrhosis, hepatic failure, or hepatocellular carcinoma [3,4,5,6,7]
During the chronic phase of HCV infection, most HCVinfected patients develop high-titer of antibodies. These antibodies were not able to control HCV infection which may be attributed to the generation of non-neutralizing HCV-specific antibodies that compete with neutralizing Abs and reduce their effectiveness. Such antibodies have been reported in other viral infections in which highly immunogenic non-neutralizing epitopes mislead the humoral immune response contributing to viral escape from neutralization [11]
Summary
Hepatitis C Virus (HCV) is a global health problem that affects almost 3% of the world’s population [1] and not less than 15% of the Egyptian population [2]. Individuals with chronic HCV infection usually remain asymptomatic and undiagnosed for decades before chronic hepatitis leads to severe fibrosis and cirrhosis, hepatic failure, or hepatocellular carcinoma [3,4,5,6,7] These long-term complications made HCV one of the leading emerging infectious diseases worldwide. During the chronic phase of HCV infection, most HCVinfected patients develop high-titer of antibodies These antibodies were not able to control HCV infection which may be attributed to the generation of non-neutralizing HCV-specific antibodies that compete with neutralizing Abs and reduce their effectiveness. Such antibodies have been reported in other viral infections in which highly immunogenic non-neutralizing epitopes mislead the humoral immune response contributing to viral escape from neutralization [11]. Several observations support the hypothesis that neutralizing antibodies may help control HCV replication [12,13]
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