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.

Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non–Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae

“…Although immunization with HIV-1 Gag along with CCL20 DNA plasmids has previously been shown to induce a Th1 response (40), our results showed that CCL20 genetic adjuvantation induced a marked Th2 skew following DNA immunization. Although two further studies investigated the use of CCL20 genetic adjuvantation of a HCV core plasmid DNA and of a foot-and-mouth disease vaccine, the IgG1 and IgG2a responses were assessed solely after Ag plus Montanide ISA 206 adjuvant boost, showing a Th1 profile (18,41). In our study, despite the use of MPLA (known to induce strong Th1 responses) the Ag-IRES-CCL20 group maintained its Th2 skewed profile following the Ag plus adjuvant topical boost.…”

“…Whether the differences in T helper responses are due to the studied Ag, the quantity of DNA used (203 less in our study compared with Ref. 18) or the adjuvant used will require further investigations. In addition, following DNA immunization Ag-IRES-CCL25, -CCL27, -CCL28, and -TNF-a induced a mixture of Th1 skewed, Th2 skewed and balanced Th1/Th2 responses which persisted post protein boost.…”

“…Eliciting an appropriate immune response at mucosal sites is likely necessary to protect from sexually transmitted pathogens such as HIV and Chlamydia, respiratory pathogens like influenza and RSV, or gastrointestinal infections caused by rotavirus, clostridium, and Salmonella. To induce mucosal immunity, strategies involving systemic and topical immunizations with chemokine adjuvants have been tested with the aim to recruit and program immune cells (8,9,11,18,28). In this study, we developed a DNA platform which allows bicistronic expression of the Ag of interest and a chosen chemokine/cytokine using an EMCV IRES.…”

“…Nucleic acid-based, and in particular DNA-based, vaccines offer a great opportunity by limiting the extent of manufacturing and long-term storage considerations. Delivered on their own, DNA plasmids expressing particular Ags do not induce high levels of immunity, but electroporation (EP) along with genetic adjuvants have proven to be effective ways of inducing strong immune responses (18,19).…”

CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents

“…Regimens using chemokines as adjuvants for DNA vaccination have been shown to act through the recruitment of DCs and other immune cells to immune inductive sites [29][30][31] . Our previous studies showed that a CCL19 DNA plasmid entered the secondary lymphoid tissues and expressed the chemokine there following intramuscular administration.…”