Enhancement of Immune Responses by Co-delivery of CCL19/MIP-3beta Chemokine Plasmid With HCV Core DNA/Protein Immunization

Christine Hartoonian; Zargham Sepehrizadeh; Mojtaba Tabatabai Yazdi; Yong Suk Jang; Lida Langroudi; Parisa Amir Kalvanagh; Babak Negahdari; Ali Karami; Massoumeh Ebtekar; Kayhan Azadmanesh

doi:10.5812/hepatmon.14611

Enhancement of Immune Responses by Co-delivery of CCL19/MIP-3beta Chemokine Plasmid With HCV Core DNA/Protein Immunization

Hepat Mon. 2014 Mar 1;14(3):e14611. doi: 10.5812/hepatmon.14611. eCollection 2014 Mar.

Affiliations

¹ Department of Pharmaceutical Biotechnology and Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran ; Department of Virology, Pasteur Institute of Iran, Tehran, IR Iran.
² Department of Pharmaceutical Biotechnology and Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran.
³ Departments of Molecular Biology and Bioactive Material Sciences, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.
⁴ Department of Virology, Pasteur Institute of Iran, Tehran, IR Iran.
⁵ Department of Virology, Pasteur Institute of Iran, Tehran, IR Iran ; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, IR Iran.
⁶ Department of Immunology, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, IR Iran ; Department of Medical Biotechnology, School of Advanced Technologies, Tehran University of Medical Sciences, Tehran, IR Iran.
⁷ Department of Research Center of Molecular Biology, Baqyiatallah University of Medical Sciences, Tehran, IR Iran.
⁸ Department of Immunology, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, IR Iran.

Abstract

Background: Using molecular adjuvants offers an attractive strategy to augment DNA vaccine-mediated immune responses. Several studies have revealed that an efficient HCV vaccine model should be able to induce both humoral and cell mediated immune responses targeting the conserved regions of the virus to circumvent the immune escape mutants. The beta chemokine Macrophage Inflammatory Protein 3-beta (MIP-3beta) is a key modulator of dendritic cells (DCs) and T-cells interaction, functions during immune response induction and is secreted specifically by cells in the lymphoid tissues.

Objectives: In the present study, we questioned whether co-administration of MIP-3beta gene could enhance the immune responses to HCV core in DNA vaccination.

Materials and methods: Expression and biological activity of MIP-3beta expressing plasmid were evaluated by ELISA and transwell migration assays, respectively. HCV core DNA vaccine ± plasmid expressing MIP-3beta were electroporated subcutaneously to the front foot pads of BALB/c mice on days 0 and 14, and HCV core protein booster was applied to all core-DNA-vaccine received mice on the day 28. Both cell mediated immunity (proliferation, IFN-γ and IL-4 cytokine release, IFN-γ ELISpot and cytotoxic Granzyme B release assays) and humoral immune responses (total IgG and IgG2a/IgG1 subtyping) were evaluated ten days after final immunization.

Results: Mice covaccinated with MIP-3beta elicited an enhanced Th1 biased systemic immune response as evidenced by higher IFN-γ/IL-4 and anti-core IgG2a/IgG1 ratio, lymphoproliferation, strong cytolytic GrzB release and enhanced population of IFN-γ producing immunocytes. Likewise, the humoral immune response assumed as the total anti-core IgG level was augmented by MIP-3beta co-delivery.

Conclusions: These results exhibited the immuno potentiator effects of MIP-3beta plasmid when coadministrated with the HCV core DNA vaccine. Complimentary studies integrating MIP-3beta as a genetic adjuvant in HCV-core-DNA vaccination models are warranted.

Keywords: Adjuvants; Chemokine CCL19; Hepatitis C; Hepatitis C Antigens.