Abstract
AbstractIL-12 is known to be an essential cytokine which appears to provide protective immunity against intracellular bacteria, such as Salmonella. In this study, we investigated the possibility of developing a vaccine using IL-12 against virulent Salmonella. We used the host defense system activated by cytokine IL-12. The highly virulent Salmonella strain (Salmonella typhimurium UK-1) was transformed with cytokine-expressing plasmids. These live, wild-type pathogens were used as vaccine strains without undergoing any other biological or genetic attenuating processes. The newly developed strains induced partial protection from infections (30-40%). Of note, the interleukin-12 transformed pathogen was safe upon immunization with low doses (103 CFU), induced IgG responses, and stimulated protective immune responses against Salmonella Typhimurium in mice (80-100%). These results suggest that IL-12 induced attenuation of wild-type Salmonella in the host infection stage and vaccine development using the wild-type strain harboring IL-12 secreting plasmids may be considered as an alternative process for intracellular bacterial vaccine development without the inconvenience of time-consuming attenuation processes.
Highlights
IL-12, a heterodimeric cytokine, is composed of two subunits, p40 and p35
IL-12 is involved in differentiation of naïve CD4+ lymphocyte to the Th1 subset, which produces, IFN-gamma, as well as other cytokines
IL-12 is essential for the induction of protective immunity against intracellular bacteria, such as mycobacteria and Salmonella[10, 11]
Summary
IL-12, a heterodimeric cytokine, is composed of two subunits, p40 and p35. This cytokine is produced mainly by monocytes/macrophages and promotes the development and activity of cytotoxic T-lymphocytes, including natural killer cells, lymphokineactivated killer cells, and macrophages. Salmonella strains were first used as a bioterror agent in 1984 5 This agent was a new, modified strain of existing bacteria. Existing vaccines are developed by the attenuation of pathogens through the genetic modification process. We postulated that the infection of this lethal strain with host-stimulating cytokine might induce protective immunity. The highly virulent Salmonella strain (Salmonella typhimurium UK-1) was transformed with cytokine-expressing plasmids These live wild-type pathogens were used as vaccine strains without other biological and genetic attenuating processes. To test this hypothesis, we applied this concept to the preparation of Salmonella typhimurium vaccine in mice. S. typhimurium UK-1 is highly virulent for chickens and mice
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