Salmonella typhimurium harboring plasmid expressing interleukin-12 induced attenuation of infection and protective immune responses

Suppression of dendritic cell and T-cell activation by the pRST98 Salmonella plasmid

“…These results were consistent with studies in which IL-12 production of liver CD11c(+) cells was analyzed by flow cytometry following stimulation with S. Typhimurium (27). IL-12 is an essential cytokine, which may provide protective immunity against Salmonella, as it is a key cytokine produced by APC to stimulate a Th1-directed response (28,29). Salmonella-specific T cells developing under the influence of IL-12 produce cytokines, including IFN-γ, that enhance the bactericidal capacity of phagocytes and facilitate microbial elimination (30,31).…”

<i>Salmonella</i> and Biotechnology

“…Wild-type pathogenic S. Typhimurium UK-1 carrying an IL-12-expressing plasmid induces protection against a lethal dose of normal wild-type Salmonella [16]. These results also revealed that a wild-type Salmonella strain bearing a plasmid for secretion of IL-12 may be considered an alternative approach to the development of intracellular bacterial vaccines, without the inconvenience of time-consuming attenuation procedures.…”

Antigen Delivery System II

“…Although some results reported are encouraging, more detailed and well-controlled studies will be needed to better delineate how expression of these cofactors would enhance immune responses and protection, especially in regard to mucosal immune responses and protection against pathogens infecting via a mucosal surface. I should note, however, that Yoon et al (2011) discovered that engineering a commercial DNA vaccine vector to specify IL-12 synthesis to be delivered by wild-type S. Typhimurium UK-1 (low doses) resulted in attenuation of the Salmonella. Although Yoon et al (2011) suggest this as a means to attenuate virulent pathogens and transform into vaccines, I would argue that this, like over-synthesis of a recombinant antigen, is not a safe, acceptable, or reliable means for RABV attenuation, since loss in ability to synthesize IL-12 would restore virulence.…”

“…I should note, however, that Yoon et al (2011) discovered that engineering a commercial DNA vaccine vector to specify IL-12 synthesis to be delivered by wild-type S. Typhimurium UK-1 (low doses) resulted in attenuation of the Salmonella. Although Yoon et al (2011) suggest this as a means to attenuate virulent pathogens and transform into vaccines, I would argue that this, like over-synthesis of a recombinant antigen, is not a safe, acceptable, or reliable means for RABV attenuation, since loss in ability to synthesize IL-12 would restore virulence.…”