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However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge. The genetic circuits are engineered that (1) induce self\u2010lysis to release foreign antigens into target cells and (2) activate the cytosolic surveillance cGAS\u2010STING axis by releasing DNA into the cytoplasm. Delayed synthesis of the MazF interferase regulates differential mRNA cleavage, resulting in a 36\u2010fold increase in the delivery of foreign antigens and modest activation of the inflammasome, which collectively contribute to the marked maturation of antigen\u2010presenting cells (APCs). Bacteria delivering the protective antigen SaoA exhibits excellent immunogenicity and safety in mouse and pig models, significantly improving the survival rate of animals challenged with multiple serotypes of Streptococcus suis. 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