Co‐delivery of GM‐CSF gene enhances the immune responses of hepatitis C viral core protein‐expressing DNA vaccine: Role of dendritic cells

Abstract

Hepatitis C virus (HCV) infection has become a critical public health problem worldwide. In Taiwan, it has been estimated that more than 300,000 people, 2% of the general population, have HCV infection. It has been well documented that direct delivery of gene intramuscularly can generate both humoral and cellular immunity, which more closely simulates the conditions of infection. In this study, female Balb/c mice immunized with HCV core plasmid DNA with or without adjuvant GM-CSF cytokine gene could induce both cellular immune response and HCV core-specific antibody titers after injection. Furthermore, the mice immunized with HCV core plus GM-CSF genes showed higher antibody titer and cytotoxic T cell activity compared to those of mice immunized with HCV core gene only (P < 0.05). To explore the effect of GM-CSF gene, the mice were immunized with reporter gene and cytokine gene plasmid. Increased levels of reporter protein and infiltrating cells around muscle tissue were noted. Moreover, the protein could be detected in inguinal node 24 hr after injection, especially in mice immunized with HCV/core plasmid plus GM-CSF gene. It was also observed that reporter protein expressing CD11c(+) dendritic cells could be seen in the inguinal node. These data suggest that the GM-CSF gene did enhance HCV core specific immune response when co-immunized with HCV core DNA plasmid. Although more studies are needed, dendritic cells that appeared around the naked DNA injection area and that local lymph nodes might play a critical role in the immune response induced by naked DNA immunization.

Protective Immunity against Bordetella pertussis by a Recombinant DNA Vaccine and the Effect of Coinjection with a Granulocyte‐Macrophage Colony Stimulating Factor Gene

“…Although the mechanism by which GM-CSF enhances immunity is not completely understood, evidence suggests that GM-CSF may work through its effects on APCs (16). In previous studies, when GM-CSF encoding plasmids were co-inoculated with antigen encoding plasmids, immunity was enhanced (12,23,31). These results fit the expectation to increase both cellular and humoral immune responses in our experiments.…”

Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4+ and CD8+ T lymphocyte responses

“…Accumulating evidence, however, suggests that immune priming is initiated by professional APC rather than by these myocytes [8][9][10][11][12]. Since professional APC are not typically found in normal muscle tissue, they presumably migrate to the site of DNA inoculation in response to inflammatory or chemotactic signals [13][14][15]. Infiltrating APC may then either take up the plasmid DNA directly or cross-present expressed antigen to initiate immune responses [16][17][18][19].…”

“…In particular, plasmid GM-CSF has received considerable attention given its ability to enhance DNA vaccine-elicited cellular immune responses specific for a variety of antigens [13][14][15]. We have previously reported that coadministration of plasmid GM-CSF with an HIV-1 Env DNA vaccine specifically augmented DNA vaccine-elicited CD4 + T lymphocyte responses but had minimal effects on CD8 + T lymphocyte or antibody responses [14].…”

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles

“…Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to expand myeloid-derived dendritic cell (DC) populations (20,47), to augment antigeninduced humoral and cellular immune responses, and to affect the Th1/Th2 cytokine balance (45). It has been extensively used as an effective genetic and protein adjuvant to enhance immunogenicity of tumor and vaccine antigens (6,14,16,28,29,31,35,42,48,50,54,56). Another immunostimulatory molecule is CD40 ligand (CD40L), which is a surface molecule primarily expressed on mature CD4 ϩ T cells.…”