title: Modulation of hepatitis C virus core DNA vaccine immune responses by co-immunization with CC-chemokine ligand 20 (CCL20) gene as immunoadjuvant.
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.
authors: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Biotechnology Research Center, Tehran University of Medical Sciences, Enghelab Ave, 16 Azar Ave, 1417614411, Tehran, Iran, hartoonian@razi.tums.ac.ir.
authors: Christine
authors: C
authors: Hartoonian
authors: Zargham
authors: Z
authors: Sepehrizadeh
authors: Mehdi
authors: M
authors: Mahdavi
authors: Arash
authors: A
authors: Arashkia
authors: Yon Suk
authors: YS
authors: Jang
authors: Maasoumeh
authors: M
authors: Ebtekar
authors: Mojtaba Tabatabai
authors: MT
authors: Yazdi
authors: Babak
authors: B
authors: Negahdari
authors: Azita
authors: A
authors: Nikoo
authors: Kayhan
authors: K
authors: Azadmanesh
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D054418:Chemokine CCL20 / Q000235:genetics* / Q000276:immunology; D016207:Cytokines; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D054418:Chemokine CCL20; D016207:Cytokines; D004279:DNA, Viral; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus