COMPARISON OF IMMUNOGENICITY OF HCV CD8-EPITOPES AS A SINGLE EPITOPE, MIXTURE OF EPITOPES AND POLYTOPE PEPTIDE

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MOTEVALLI FATEMEH; MEMARNEJADIAN ARASH; SADAT SEYED MEHDI; BAHRAMALI GOLNAZ; ROOHVAND FARZIN

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Journal: Pathobiology Research Year:2012 | Volume:14 | Issue:4 Page(s): 62-71

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Title

COMPARISON OF IMMUNOGENICITY OF HCV CD8-EPITOPES AS A SINGLE EPITOPE, MIXTURE OF EPITOPES AND POLYTOPE PEPTIDE

Author(s)

Keywords

HCVQ3

EPITOPEQ2

PEPTIDE VACCINEQ3

IMMUNODOMINANCEQ2

POLYTOPEQ2

Abstract

Objective: Animal studies show that vaccination with EPITOPE-based peptides results in protective immunity. However, IMMUNODOMINANCE should be regarded as a major challenge in this area. Considering the advantages of epitopic-vaccines against hepatitis C virus (HCV) infection, herein, we compared the occurrence of IMMUNODOMINANCE following mice immunization with three different HCV epitopic-peptide formulations.Methods: We synthesized four CD8+ epitopic-peptides (C1, E6, N, E4) that were derived from HCV-antigens. A POLYTOPE-peptide (C1E6NE4) spanning fusion of EPITOPEs was designed based on immunoinformatics analyses for optimum proteasomal cleavage. BALB/c mice received three subcutaneous injections that contained 10 mg of peptide (minimal EPITOPEs, or mixture of four EPITOPEs or long-polytope) formulated with CpG (50 mg) and Montanide-ISA720 (70%) adjuvants in the tail-base at three-week intervals. Considering the H2-Dd (BALB/c)-restriction of C1 and E4-epitopes, three weeks after the last injection splenocytes from vaccinated animals were subjected to IFNg/IL4 ELISpot assays in the presence of C1 and E4-peptides.Results: All vaccinated animals promoted Th1-oriented responses as evidenced by detection of IFNg-secreting cells and a low-level of IL4 secretion. Mice injected with minimal CTL-epitopes provoked stronger responses, however, due to the higher affinity of E4-epitope for H2-Dd, frequency of E4-specific cells was considerably higher than C1-specific ones, showing some level of IMMUNODOMINANCE. Interestingly, animals vaccinated with POLYTOPE-peptide developed high-quality balanced responses against both C1 and E4-epitopes, however at a lower intensity.Conclusion: These results supported the superiority of POLYTOPE-peptides over minimal EPITOPEs, yet emphasized the key role of POLYTOPE design and optimization to avoid EPITOPE dominancy.

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APA: Copy

MOTEVALLI, FATEMEH, MEMARNEJADIAN, ARASH, SADAT, SEYED MEHDI, BAHRAMALI, GOLNAZ, & ROOHVAND, FARZIN. (2012). COMPARISON OF IMMUNOGENICITY OF HCV CD8-EPITOPES AS A SINGLE EPITOPE, MIXTURE OF EPITOPES AND POLYTOPE PEPTIDE. PATHOBIOLOGY RESEARCH (MODARES JOURNAL OF MEDICAL SCIENCES), 14(4), 62-71. SID. https://sid.ir/paper/80956/en

Vancouver: Copy

MOTEVALLI FATEMEH, MEMARNEJADIAN ARASH, SADAT SEYED MEHDI, BAHRAMALI GOLNAZ, ROOHVAND FARZIN. COMPARISON OF IMMUNOGENICITY OF HCV CD8-EPITOPES AS A SINGLE EPITOPE, MIXTURE OF EPITOPES AND POLYTOPE PEPTIDE. PATHOBIOLOGY RESEARCH (MODARES JOURNAL OF MEDICAL SCIENCES)[Internet]. 2012;14(4):62-71. Available from: https://sid.ir/paper/80956/en

IEEE: Copy

FATEMEH MOTEVALLI, ARASH MEMARNEJADIAN, SEYED MEHDI SADAT, GOLNAZ BAHRAMALI, and FARZIN ROOHVAND, “COMPARISON OF IMMUNOGENICITY OF HCV CD8-EPITOPES AS A SINGLE EPITOPE, MIXTURE OF EPITOPES AND POLYTOPE PEPTIDE,” PATHOBIOLOGY RESEARCH (MODARES JOURNAL OF MEDICAL SCIENCES), vol. 14, no. 4, pp. 62–71, 2012, [Online]. Available: https://sid.ir/paper/80956/en

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