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

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.

Immunization with HSV-2 gB-CCL19 Fusion Constructs Protects Mice against Lethal Vaginal Challenge

“…In this regard, following CCL19 immunization, T cell-mediated immune responses might be upregulated more directly than humoral responses (16,30). Given the central roles of cytokines secreted by activated immunocytes in defining the subsequent immune response, we evaluated gB-specific Th1-and Th2-like cellular immune responses by measuring the production of Th1-associated (IL-2, TNF, IFN-g) and Th2-associated (IL-4, IL-5) cytokines.…”

“…CCL19, through interactions with its cognate receptor CCR7, plays a pivotal role in recruiting immunocytes, including T cells (16), B cells (19,20), and mature dendritic cells (DCs) (21)(22)(23)(24)(25)(26), to secondary lymphoid organs, such as endothelial venules of lymph nodes and Peyer's patches, as well as the T cell zones of spleen and lymph nodes (18,19,21,(26)(27)(28)(29)(30). The CCL19-CCR7 pathway is also important in mediating lymphocyte colocalization and Ag-specific T cell activation (26), as well as in directing the differentiation of DCassisted B cells into Ab-secreting cells (ASCs) (16,31).…”

“…The CCL19-CCR7 pathway is also important in mediating lymphocyte colocalization and Ag-specific T cell activation (26), as well as in directing the differentiation of DCassisted B cells into Ab-secreting cells (ASCs) (16,31). CCL19 as a molecular adjuvant was proved to be useful in several immunization models and is capable of promoting Ag-specific humoral and cellular immune responses in combination with vaccine candidates, including HSV-1 gB (14), HIV-1 Env (16), pseudorabies virus gB (32), and HCV core DNA (30).…”

CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients

“…CMV vaccine candidates reaching phase 2 clinical trials have achieved some success in stimulating either cellular or humoral responses, but not both simultaneously . Chemokines have been explored as a new class of vaccine adjuvant, and have already been tested in animal models for hepatitis C , malaria , and HIV . This strategy has already been specifically validated for a CCR5‐targeting chemokine‐antigen fusion DNA vaccine in mice, which resulted in enhanced CD4+ T cell, CD8+ T cell, and B cell responses .…”

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

“…CCL19 gene-deleted mice have defects in DC localization [16] . Several studies showed that enhanced humoral and cellular immunity were obtained by the codelivery of plasmids encoding CCL19 along with DNA vaccines [17][18][19] . Our previous study demonstrated that the codelivery of the CCL19 gene with the anti-caries DNA vaccine pCIA-P significantly augmented systemic immune responses.…”