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Mol Immunol. 2019 Jul;111:152-161. doi: 10.1016/j.molimm.2019.04.009. Epub 2019 May 1.

A non-pathogenic Leishmania tarentolae vector based- HCV polytope DNA vaccine elicits potent and long lasting Th1 and CTL responses in BALB/c mice model.

Author information

1
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
2
Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
3
Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
4
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ksamimirad@sina.tums.ac.ir.

Abstract

Despite successful anti-viral (DAAs) treatment of Hepatitis C virus (HCV) infection, recent data indicated the need for an effective vaccine. Preexisting anti-vector immunity is an obstacle for application of live vectors for antigen delivery and development of effective T-cell based HCV vaccines. Herein, we report construction of recombinant Leishmania tarentolae, a lizard (non-human) parasite, expressing an HCV polytope DNA, PT-NT(gp96), encoding for several immunogenic HCV epitopes and evaluation of its immunogenicity in three different prime/boost immunization groups (G) of BALB/c mice. Homologous prime/boost immunization by L.tarentolae-PT-NT(gp96) either with or without CpG (G1 and G2 respectively) and heterologous immunization with a PT-NT(gp96) encoding-pCDNA plasmid followed by L.tarentolae-PT-NT (G3) was undertaken. Immune responses were measured three and nine weeks (W) post immunization. Splenocytes (cultured with antigen-stimulant) of mice in G1 showed the highest percentage of specific CTL-cytolytic activity compared to G2 and G3 at both short (W3:70.98% versus 41.29% and 13.12%) and long (W9: 50% versus 24.5% and 20%) term periods, accompanied with high levels of secreted IFN-γ. Comparison of IFN-γ, IL-4, IL-17 and TNF-α cytokines levels obtained from the supernatant of antigen-stimulated splenocytes as well as antibodies level (as IgG1/IgG2a ratio; obtained from sera of immunized mice) indicated higher Th1 oriented responses for G1, G2 groups and balanced Th1-Th17 for G3. Results indicated the potential of L.tarentolae (+CpG), as a non-pathogenic live vaccine vector, for delivery and enhancement of immune responses against HCV-polytope antigens.

KEYWORDS:

CpG; Leishmania tarentolae; Prime-boost; Vaccine; hepatitis C virus

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