Modulation of Immune Responses to a HIV-1 Nucleic Acid Vaccine by Interleukin-18 DNA Immunization

To investigate the effect of interleukin-18 (IL-18) DNA immunization on immune response induced by Human immunodeficiency virus 1(HIV-1) nucleic acid vaccine (DNA vaccine), the recombinant expression vector pVAX1-IL-18 was constructed by inserting the IL-18 gene into the eukaryotic expression vector pVAX1. Balb/c mice were immunized with pCI-neoGAG alone or co-administered with the DNA encoding for IL-18. Their sera were collected for analyzing anti-HIV antibody and IFN-γ by ELISA, and spleen cells were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay, respectively. Restriction enzymes digestion analysis and DNA sequencing results revealed that the recombinant expression vector pVAX1-IL-18 has been constructed successfully. The anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-18 were lower than that of mice immunized with pCI-neoGAG alone (P0.01). In contrast, the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-18 was higher than that of mice immunized with pCI-neoGAG alone (P0.01). Furthermore, compared with mice injected with pCI- neoGAG alone, the specific CTL cytotoxity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for IL-18 were significantly enhanced (P0.01). The DNA encoding for IL-18 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune responses elicited in mice. However, the DNA encoding for IL-18 may down-regulate the humoral responses.