Author/Authors :
Hartoonian, Christine tehran university of medical sciences tums - Biotechnology Research Center, Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Hartoonian, Christine Pasteur Institute of Iran - Department of Virology, ايران , Sepehrizadeh, Zargham tehran university of medical sciences tums - Biotechnology Research Center, Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Tabatabai Yazdi, Mojtaba tehran university of medical sciences tums - Biotechnology Research Center, Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Jang, Yong Suk Chonbuk National University - Institute for Molecular Biology and Genetics - Departments of Molecular Biology and Bioactive Material Sciences, Korea , Langroudi, Lida Pasteur Institute of Iran - Department of Virology, ايران , Amir Kalvanagh, Parisa Pasteur Institute of Iran - Department of Virology, ايران , Amir Kalvanagh, Parisa tarbiat modares university - Faculty of Medical Sciences - Department of Immunology, تهران, ايران , Negahdari, Babak tarbiat modares university - Faculty of Medical Sciences - Department of Immunology, تهران, ايران , Negahdari, Babak tehran university of medical sciences tums - School of Advanced Technologies - Department of Medical Biotechnology, تهران, ايران , Karami, Ali baqiyatallah university of medical sciences - Department of Research Center of Molecular Biology, ايران , Ebtekar, Massoumeh tarbiat modares university - Faculty of Medical Sciences - Department of Immunology, تهران, ايران , Azadmanesh, Kayhan Pasteur Institute of Iran - Department of Virology, ايران
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.
