Co-Immunization of Plasmid DNA Encoding IL-12 and IL-18 with Bacillus Calmette-Guérin Vaccine against Progressive Tuberculosis
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Purpose: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL_12 or IL_18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model. Materials and Methods: Plasmid DNA vaccine constructs encoding IL_12 or IL_18 were constructed and mice were immunized with the BCG vaccine or with IL_12 DNA or IL_18 DNA vaccine constructs together with the BCG vaccine. Results: The BCG vaccine induced high level of interferon gamma (IFN-γ) but co-immunization of IL_12 or IL_18 DNA vaccine constructs with the BCG vaccine induced significantly higher level of IFN-γ than a single BCG vaccine. The BCG vaccine was highly protective at early stage of M. tuberculosis infection, but its protective efficacy was reduced at later stage of infection. The co-immunization of IL_12 DNA vaccine constructs with the BCG vaccine was slightly more protective at early stage of infection and was significantly more protective at later stage infection than a single BCG vaccine. Conclusion: Co-immunization of IL_12 DNA vaccine with the BCG vaccine induced more protective immunity and was more effective for protection against progressive infection of M. tuberculosis.
Abstract
Purpose: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL_12 or IL_18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model. Materials and Methods: Plasmid DNA vaccine constructs encoding IL_12 or IL_18 were constructed and mice were immunized with the BCG vaccine or with IL_12 DNA or IL_18 DNA vaccine constructs together with the BCG vaccine. Results: The BCG vaccine induced high level of interferon gamma (IFN-γ) but co-immunization of IL_12 or IL_18 DNA vaccine constructs with the BCG vaccine induced significantly higher level of IFN-γ than a single BCG vaccine. The BCG vaccine was highly protective at early stage of M. tuberculosis infection, but its protective efficacy was reduced at later stage of infection. The co-immunization of IL_12 DNA vaccine constructs with the BCG vaccine was slightly more protective at early stage of infection and was significantly more protective at later stage infection than a single BCG vaccine. Conclusion: Co-immunization of IL_12 DNA vaccine with the BCG vaccine induced more protective immunity and was more effective for protection against progressive infection of M. tuberculosis.
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