title: Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery.
abstract: Type III protein secretion systems are being considered for vaccine development as virtually any protein antigen can be engineered for delivery by these nanomachines into the class I antigen presentation pathway to stimulate antigen-specific CD8(+) T cells. A limitation in the use of this system is that it requires live virulence-attenuated bacteria, which may preclude its use in certain populations such as children and the immunocompromised. Here we report the engineering of the Salmonella Typhimurium type III secretion system in achromosomal, non-replicating nanoparticles derived from bacterial minicells. The engineered system is shown to be functional and capable of delivering heterologous antigens to the class I antigen presentation pathway stimulating immune responses both in vitro and in vivo. This antigen delivery platform offers a novel approach for vaccine development and cellular immunotherapy.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Carleton
authors.forename: María
authors.initials: M
authors.lastname: Lara-Tejero
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005818:Genetic Engineering; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012486:Salmonella typhimurium / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000941:Antigens; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D010047:Ovalbumin