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01.01.2015 | Original Article

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

verfasst von: Leila Pishraft-Sabet, Anna D. Kosinska, Sima Rafati, Azam Bolhassani, Tahereh Taheri, Arash Memarnejadian, Seyed-Moayed Alavian, Michael Roggendorf, Katayoun Samimi-Rad

Erschienen in: Archives of Virology | Ausgabe 1/2015

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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-D^d-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.

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Titel: Enhancement of HCV polytope DNA vaccine efficacy by fusion to an N-terminal fragment of heat shock protein gp96
verfasst von: Leila Pishraft-Sabet
Anna D. Kosinska
Sima Rafati
Azam Bolhassani
Tahereh Taheri
Arash Memarnejadian
Seyed-Moayed Alavian
Michael Roggendorf
Katayoun Samimi-Rad
Publikationsdatum: 01.01.2015
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 1/2015
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-014-2243-8

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