Archives of Virology

, Volume 160, Issue 1, pp 141–152 | Cite as

Enhancement of HCV polytope DNA vaccine efficacy by fusion to an N-terminal fragment of heat shock protein gp96

  • Leila Pishraft-Sabet
  • Anna D. Kosinska
  • Sima Rafati
  • Azam Bolhassani
  • Tahereh Taheri
  • Arash Memarnejadian
  • Seyed-Moayed Alavian
  • Michael Roggendorf
  • Katayoun Samimi-RadEmail author
Original Article


Induction of a strong hepatitis C virus (HCV)-specific immune response plays a key role in control and clearance of the virus. A polytope (PT) DNA vaccine containing B- and T-cell epitopes could be a promising vaccination strategy against HCV, but its efficacy needs to be improved. The N-terminal domain of heat shock protein gp96 (NT(gp96)) has been shown to be a potent adjuvant for enhancing immunity. We constructed a PT DNA vaccine encoding four HCV immunodominant cytotoxic T lymphocyte epitopes (two HLA-A2- and two H2-Dd-specific motifs) from the Core, E2, NS3 and NS5B antigens in addition to a T-helper CD4+ epitope from NS3 and a B-cell epitope from E2. The NT(gp96) was fused to the C- or N-terminal end of the PT DNA (PT-NT(gp96) or NT(gp96)-PT), and their potency was compared. Cellular and humoral immune responses against the expressed peptides were evaluated in CB6F1 mice. Our results showed that immunization of mice with PT DNA vaccine fused to NT(gp96) induced significantly stronger T-cell and antibody responses than PT DNA alone. Furthermore, the adjuvant activity of NT(gp96) was more efficient in the induction of immune responses when fused to the C-terminal end of the HCV DNA polytope. In conclusion, the NT(gp96) improved the efficacy of the DNA vaccine, and this immunomodulatory effect was dependent on the position of the fusion.


Enhanced Green Fluorescent Protein Humoral Immune Response Heat Shock Protein Gp96 Enhanced Green Fluorescent Protein Signal CB6F1 Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was funded and supported by Grant No. 13270 from Tehran University of Medical Sciences (TUMS) and Grant No. 90-803 from Baqiyatallah University of Medical Science.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Leila Pishraft-Sabet
    • 1
    • 2
  • Anna D. Kosinska
    • 3
  • Sima Rafati
    • 4
  • Azam Bolhassani
    • 5
  • Tahereh Taheri
    • 4
  • Arash Memarnejadian
    • 5
  • Seyed-Moayed Alavian
    • 6
  • Michael Roggendorf
    • 3
  • Katayoun Samimi-Rad
    • 1
    Email author
  1. 1.Department of Virology, School of Public HealthTehran University of Medical SciencesTehranIslamic Republic of Iran
  2. 2.Razi Vaccine and Serum Research InstituteKarajIran
  3. 3.Institute of VirologyUniversity Hospital of EssenEssenGermany
  4. 4.Molecular Immunology and Vaccine Research LaboratoryPasteur Institute of IranTehranIran
  5. 5.Hepatitis and HIV LaboratoryPasteur Institute of IranTehranIran
  6. 6.Research Center for Gastroenterology and Liver DiseaseBaqiyatallah University of Medical SciencesTehranIran

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