Designing & producing polytope DNA vaccine containing HBsAg gene for the induction of protective immunity against hepatitis C

Memarnejadian, A. and Roohvand, F. and Motevalli, F. and Aghasadeghi, M.R. (2009) Designing & producing polytope DNA vaccine containing HBsAg gene for the induction of protective immunity against hepatitis C. Feyz Journal of Kashan University of Medical Sciences, 13.

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Official URL: http://feyz.kaums.ac.ir/article-1-778-en.html
DOI: UNSPECIFIED

Abstract

Background: Considering the immunosuppressive effects and prevalent mutations in some HCV antigens, induction of CD8+ T cell responses is focused on conserved and critical epitopes which as a multi-epitope vaccine can prevent the chronic nature of the disease. Materials and Methods: Two immunodominant HLA-A2-restricted human epitopes (E2614-622 and NS31406-1415) and two H-2d-restricted mouse epitopes (core132-142 and E2405-414) were designed in a sequential tandem, predicted by immunoinformatic analyses. Following the synthesis, related nucleotide sequence was cloned into the pcDNA3.1 vector with and without the fusion of hepatitis B surface antigen (HBsAg). Two constructed plasmids (pcDNA3.1.HPOL and pcDNA3.1.POL, respectively) were evaluated for the protein expression and secretion in Cos-7 cell line. After the vaccination of BALB/c mice (n=6 in each group) with different DNA and peptide immunization regimens, CD8+ T cell activity as well as the type and protective potency of the induced responses were evaluated. Results: Despite the induction of epitope-specific responses in pcDNA3.1.POL injected mice, the group immunized with pcDNA3.1.HPOL indicated a significant increase in the number and activity of CD8+ T cells (P<0.05). Peptide boosting of this group (formulated in two human-compatible adjuvant) still led to the more activation of CD8+ cells, induction of Th1 response and the inhibition of tumor model growth (P<0.05). Conclusion: Fusion of HBsAg as a particle-forming sequence and the source of helper epitopes along the DNA-prime/peptide-boosting immunization regimen are proposed as two promising strategies to improve the CTL multi-epitope vaccines against HCV.

Item Type: Article
Subjects: Immunology and Microbiology
Divisions: Feyz journal
Depositing User: ART . editor
Date Deposited: 10 May 2017 14:54
Last Modified: 22 May 2017 13:37
URI: http://eprints.kaums.ac.ir/id/eprint/2011

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