title: Immunogenicity of Multi-Epitope DNA and Peptide Vaccine Candidates Based on Core, E2, NS3 and NS5B HCV Epitopes in BALB/c Mice.
abstract: BACKGROUND
  Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV.
  
  
  OBJECTIVE
  Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice.
  
  
  METHODS
  In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+ T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+ epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses.
  
  
  RESULTS
  Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e. 3 weeks after the last immunization; 37.61 ± 2.39 vs. 14.43 ± 0.43, P < 0.05). Moreover, group 2 had a higher IFN-γ/IL-4 ratio compared to group 1, suggesting a shift toward Th1 response. In addition, in the present study, induced immune responses were long lasting and stable after 9 weeks of the last immunization.
  
  
  CONCLUSIONS
  Evaluation of multi-epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.
authors.affiliation: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran ; Razi Vaccine and Serum Research Institute, Karaj, IR Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Pishraft Sabet
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, IR Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Hepatitis and HIV Laboratory, Pasteur Institute of Iran, Tehran, IR Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Memarnejadian
authors.affiliation: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Talat
authors.initials: T
authors.lastname: Mokhtari Azad
authors.affiliation: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Asgari
authors.affiliation: Department of Nano Medicine, School of Advanced Technologies in Medicine, Tehran, IR Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Rahimnia
authors.affiliation: Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran ; Middle East Liver Disease Center (MELD), Tehran, IR Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, IR Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
authors.affiliation: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Samimi Rad
keywords: Electroporation; Epitope; Prime-Boost; Vaccine