Immunogenicity of Multi-Epitope DNA and Peptide Vaccine Candidates Based on Core, E2, NS3 and NS5B HCV Epitopes in BALB/c Mice

authors:

avatar Leila Pishraft Sabet 2 , avatar Tahereh Taheri 3 , avatar Arash Memarnejadian 4 , avatar Talat Mokhtari Azad 1 , avatar Fatemeh Asgari 1 , avatar Ramin Rahimnia 5 , avatar Seyed Moayed Alavian 7 , avatar Sima Rafati 3 , avatar Katayoun Samimi Rad 1 , *

Razi Vaccine and Serum Research Institute, Karaj, IR Iran
Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, IR Iran
Hepatitis and HIV Laboratory, Pasteur Institute of Iran, Tehran, IR Iran
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
Department of Nano Medicine, School of Advanced Technologies in Medicine, Tehran, IR Iran
Middle East Liver Disease Center (MELD), Tehran, IR Iran

how to cite: Pishraft Sabet L, Taheri T, Memarnejadian A, Mokhtari Azad T, Asgari F, et al. Immunogenicity of Multi-Epitope DNA and Peptide Vaccine Candidates Based on Core, E2, NS3 and NS5B HCV Epitopes in BALB/c Mice. Hepat Mon. 2014;14(10):22215. doi: 10.5812/hepatmon.22215.

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.

Objectives:

Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice.

Materials and 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-? 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-?/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.

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