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Improvement in T helper 1‐related immune responses in BALB/c mice immunized with an HIV‐1 gag plasmid combined with a chimeric plasmid encoding interleukin‐18 and flagellin

Both flagellin (fliC) and IL‐18 (INF‐γ‐inducing factor) have been developed as adjuvants for improving immunogenicity in DNA‐vaccinated hosts. An HIV‐1 gag plasmid encodes a protein harboring broad epitopes for cytotoxic T‐lymphocytes. In this study, the immunogenicity of BALB/c mice immunized with an HIV‐1 gag plasmid (pVAX/gag) combined with a chimeric plasmid encoding IL‐18 fused to flagellin (pcDNA3/IL‐18_fliC) or a single plasmid encoding IL‐18 (pcDNA3/IL‐18) and/or flagellin (pcDNA3/fliC) was assessed. Through in vitro transcription and translation, it was demonstrated that both mRNA and protein were appropriately expressed by each construct. The IL‐18 and flagellin fusion protein, which could be detected in supernatants from transfected cells, was effective in inducing IFN‐γ by lymphocytes. Following i.m. immunization, expressions of flagellin or IL‐18 were detected in muscle cells by immunohistochemistry analysis from 72 hr. At 12 weeks post‐immunization, both gag‐specific IgG in sera and spleen cell proliferation were high in all murine groups. However, the IgG2a/IgG1 ratio, Th1 cytokine (IL‐2 and IFN‐γ) production and proportion of gag‐specific CD3+CD8+ IFN‐γ‐secreting cells were significantly higher in the murine group co‐immunized with pVAX/gag plasmid and pcDNA3/IL‐18_fliC than in the mice immunized with pVAX/gag plasmid combined with either pcDNA3/fliC or pcDNA3/IL‐18 plasmid or both. These findings suggest that a chimeric plasmid encoding IL‐18 fused to flagellin can be used as an adjuvant‐like plasmid to improve the Th1 immune response, particularly for induction of CD3+CD8+ IFN‐γ‐secreting cells in gag plasmid‐vaccinated mice.