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The Salmonella-based vaccine delivery platform utilizes attenuated strains of Salmonella enterica, such as serovar Typhi or Typhimurium, to deliver heterologous antigens or therapeutic payloads directly to the immune system (PMID: 25601457). These bacteria are genetically modified to be non-pathogenic, often through the deletion of essential metabolic or virulence genes like aroA or phoP/phoQ, while retaining their ability to invade M cells in the intestinal Peyer's patches (PMID: 11894050). Once internalized by antigen-presenting cells, the bacteria express the target antigens, stimulating robust mucosal (IgA), systemic (IgG), and cellular (Th1/CD8+) immune responses (PMID: 30108713). This platform is highly versatile, serving as the basis for the oral typhoid vaccine Ty21a and as a promising vector for cancer immunotherapy. In oncology, Salmonella's natural affinity for the hypoxic and nutrient-rich environment of solid tumors allows for the localized delivery of immunomodulators or pro-apoptotic factors (PMID: 29330111). The intrinsic presence of pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide further enhances the platform's efficacy by acting as a built-in adjuvant.
The platform functions by utilizing attenuated Salmonella as a Trojan horse to deliver genetic material or proteins to the gut-associated lymphoid tissue (GALT). Upon oral ingestion, the bacteria are sampled by M cells and transported to underlying dendritic cells and macrophages. The bacteria then escape or survive within the phagosome to express heterologous antigens, which are processed and presented via MHC class I and II pathways, triggering a comprehensive immune response involving secretory IgA, systemic antibodies, and cytotoxic T cells (PMID: 25601457, PMID: 30108713).
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