Salmonella type III-mediated heterologous antigen delivery: A versatile oral vaccination strategy to induce cellular immunity against infectious agents and tumors

Evaluation of Salmonella enterica Type III Secretion System Effector Proteins as Carriers for Heterologous Vaccine Antigens

“…Several attenuated carrier strains have been deployed for expression and delivery of various viral, bacterial, or parasitic antigens for vaccination (16). Live attenuated strains of Salmonella that synthesize and secrete foreign antigens were developed as vaccines for a number of infectious diseases and cancer treatment (19). Moreover, the use of live attenuated Salmonella to deliver recombinant antigens to the immune system is an attractive strategy for the construction of multivalent vaccines (17).…”

Concomitant Tumor and Autoantigen Vaccination Supports Renal Cell Carcinoma Rejection

“…For DNA vaccination, we chose attenuated Salmonella typhimurium that were transformed with an eukaryotic expression vector, such that the cDNA is transcribed in the host's macrophages. There is evidence that the transcribed Ag will also be taken up by resident DCs, such that peptides of the relevant Ag will be presented in MHC-I (macrophages) and MHC-II (DC) molecules, which would allow for Th cell and CTL activation (24,25). Our work indicates that activation of CTL is dominating.…”

“…As GOLGA4-specific Abs have been detected in all tested RCC patients' sera (32), and RENCA cell express GOLGA4, this autoantigen appeared well suited to examine whether autoantigen-specific Th cells support tumor Ag-specific CTLs, provided the tumor cell expresses the autoantigen. We chose transformed, attenuated SL typhimurium for autoantigen covaccination, as eukaryotic vector-transformed SL has repeatedly been demonstrated to be a potent vaccine (22,(24)(25)(26). Expectedly, draining LNCs and TILs of SL-GOLGA4-vaccinated mice contained GOLGA4-specific Th cells and CTLs.…”

“…Thus, as demonstrated by the increased proliferative activity of LNCs from RENCA-bearing mice vaccinated with RENCA lysate-pulsed DCs, DCs will present tumor Ag-as well as autoantigen-derived peptides, which amplifies Th cell activation and thereby CTL activity (61). In addition, SLs themselves are a strong immunogen (58) and will first be presented by MHC-I on peritoneal macrophages (24,25). Thus, it is possible that increased trogocytosis of CD8 + cells in tumor-free mice is, at least partly, tumor Ag and autoantigen independent and relates to the vaccine carrier (SL)-induced inflammatory response.…”

YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal

“…Thus, in addition to the well-studied T3S-associated "classical" N-terminal secretion signals, we identified a C-terminal secretion signal that mediates secretion of both endogenous and exogenous proteins. The ability of T3SS to export proteins directly from the bacterial cytoplasm into the extracellular medium or into the host cell cytosol has been exploited for heterologous protein production or antigen delivery during vaccination (46,47). In this context, the newly identified C-terminal T3S signal may have interesting biotechnological applications for production of proteins with N-terminal region that cannot be modified without affecting the protein functionality.…”