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Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

By Yasmine S El Abd, Ashraf A Tabll, Noha G Bader El Din, Alaa El-Dien S Hosny, Rehab I Moustafa, Reem El-Shenawy, Khaled Atef and Mostafa K El-Awady

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

Topics: Research
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:3179750
Provided by: PubMed Central

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Citations

  1. (1987). A: A simple, non-chromatographic procedure to purify immunoglobulins from serum and ascites fluid.
  2. (2009). al: CD81 is dispensable for Hepatitis C virus cell-to-cell transmission in hepatoma cells.
  3. (2009). al: Conserved peptides within the E2 region of Hepatitis C virus induce humoral and cellular responses in goats. Virol J
  4. (2001). al: Estimating progression to cirrhosis in chronic Hepatitis C virus infection. Hepatology
  5. (2010). al: Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes.
  6. (2006). al: Immunogenicity and safety of a novel therapeutic Hepatitis C virus (HCV) peptide vaccine: A randomized, placebo controlled trial for dose optimization in 128 healthy subjects. Vaccine
  7. (2001). BD: Hepatitis C virus infection.
  8. (1999). Clinical outcomes after Hepatitis C infection from contaminated anti-d immune globulin. Irish hepatology research group.
  9. (1989). Elazhary Y: Purification of IgG from serum with caprylic acid and ammonium sulphate precipitation is not superior to ammonium sulphate precipitation alone. Comp Immunol Microbiol Infect Dis
  10. (2007). Epidemiology of Hepatitis C virus infection.
  11. (2007). et al: Hepatitis C virus epitope-specific neutralizing antibodies in igs prepared from human plasma. Proc Natl Acad Sci USA
  12. et al: Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread.
  13. (2005). et al: Outcome in a Hepatitis C (genotype 1b) single source outbreak in germany‚Äďa 25-year multicenter study.
  14. (2008). et al: Therapeutic vaccination of chronic Hepatitis C nonresponder patients with the peptide vaccine ic41. Gastroenterology
  15. (2006). Hengartner H: Antiviral antibody responses: The two extremes of a wide spectrum. Nat Rev Immunol
  16. (2007). Morbidity and mortality in paid austrian plasma donors infected with Hepatitis C at plasma donation in the 1970s. J Hepatol
  17. (2000). The natural history of Hepatitis C virus infection: Host, viral, and environmental factors. JAMA
  18. (2006). Treating viral Hepatitis C: Efficacy, side effects, and complications. Gut