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Modulation of hepatitis C virus core DNA vaccine immune responses by co-immunization with CC-chemokine ligand 20 (CCL20) gene as immunoadjuvant

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Abstract

Plasmid DNA vaccination is a promising vaccine platform for prevention and treatment of infectious disease. Enhancement of the DNA vaccine potency by co-inoculation of immunoadjuvant has been shown to be an effective strategy. Modulation of dendritic cells and T-cells locomotion and trafficking to prime an immune response is mediated by distinct chemokines. The recent study was designed to elucidate the adjuvant activity of plasmid expressing CC-chemokine ligand 20 (pCCL20) in co-inoculation with hepatitis C virus (HCV) core DNA vaccine immunization. pCCL20 was constructed and evaluated for its functional expression. Sub-cutaneous inoculation of pCCL20 with HCV core DNA vaccine was performed via electroporation in BALB/c mice on day 0 and 14 and a HCV core protein booster was applied on day 28. On week after final immunization, both humoral and cell-mediated immune responses were assessed by indirect ELISA for core specific antibodies, lymphocyte proliferation, cytokine ELISA/ELISpot and cytotoxic Grenzyme B (GrzB) release assays. Mice were co-immunized with pCCL20 developed higher levels of core specific IFN-γ/IL-4 ratio and IL-2 release, IFN-γ producing cells, lymphocyte proliferation and cytotoxic Grenzyme B release in both draining lymph nodes and spleen cells of immunized mice. The core-specific serum total IgG and IgG2a/IgG1 ratio were significantly higher when the pCCL20 was co-inoculated. These results suggest the potential of CCL20 chemokine as vaccine adjuvant to enhance Th1 mediated cellular and humoral immune responses in HCV core DNA immunization.

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Acknowledgments

We thank Dr. Mahsa Rasekhian and Dr. S.M. Hossein Etemadzadeh for their technical assistance. Financial support was provided by Faculty of Pharmacy, Tehran University of Medical Sciences and partly was supported by Grants of Virology Department of Pasteur Institute of Iran.

Conflict of interest

The authors declare any conflict of interest and financial disclosure.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Biotechnology Research Center, Tehran University of Medical Sciences, Enghelab Ave, 16 Azar Ave, 1417614411, Tehran, Iran

    Christine Hartoonian, Zargham Sepehrizadeh & Mojtaba Tabatabai Yazdi

  2. Department of Virology, Pasteur Institute of Iran, 69 Pasteur Ave., Kargar Ave., 1316943551, Tehran, Iran

    Mehdi Mahdavi, Arash Arashkia, Babak Negahdari & Kayhan Azadmanesh

  3. Department of Molecular Biology, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, 561-756, Korea

    Yon Suk Jang

  4. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Ale Ahmad and Chamran Highways Cross, P.O. Box 1415-331, Tehran, Iran

    Maasoumeh Ebtekar

  5. Department of Medical Biotechnology, School of Advanced Technologies, Tehran University of Medical Sciences, #88, Italy Avenue, 1417755469, Tehran, Iran

    Babak Negahdari

  6. Department of Pathology, Razi Hospital, Tehran University of Medical Sciences, Vahdat Eslami St., Tehran, Iran

    Azita Nikoo

Authors
  1. Christine Hartoonian
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  2. Zargham Sepehrizadeh
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  3. Mehdi Mahdavi
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  6. Maasoumeh Ebtekar
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  7. Mojtaba Tabatabai Yazdi
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  10. Kayhan Azadmanesh
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Correspondence to Kayhan Azadmanesh.

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Hartoonian, C., Sepehrizadeh, Z., Mahdavi, M. et al. Modulation of hepatitis C virus core DNA vaccine immune responses by co-immunization with CC-chemokine ligand 20 (CCL20) gene as immunoadjuvant. Mol Biol Rep 41, 5943–5952 (2014). https://doi.org/10.1007/s11033-014-3470-5

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  • DOI: https://doi.org/10.1007/s11033-014-3470-5

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