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Enhancement of Hcv Polytope Dna Vaccine Efficacy by Fusion to an N-Terminal Fragment of Heat Shock Protein Gp96 Publisher Pubmed



Pishraftsabet L1, 2 ; Kosinska AD3 ; Rafati S4 ; Bolhassani A5 ; Taheri T4 ; Memarnejadian A5 ; Alavian SM6 ; Roggendorf M3 ; Samimirad K1
Authors
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Authors Affiliations
  1. 1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, P.O.Box 6446, Tehran, 14155, Iran
  2. 2. Razi Vaccine and Serum Research Institute, Karaj, 31975/148, Iran
  3. 3. Institute of Virology, University Hospital of Essen, Essen, 45122, Germany
  4. 4. Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, 13164, Iran
  5. 5. Hepatitis and HIV Laboratory, Pasteur Institute of Iran, Tehran, 13164, Iran
  6. 6. Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran

Source: Archives of Virology Published:2015


Abstract

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. © 2014, Springer-Verlag Wien.