title: Evaluation of Salmonella enterica type III secretion system effector proteins as carriers for heterologous vaccine antigens.
abstract: Live attenuated strains of Salmonella enterica have a high potential as carriers of recombinant vaccines. The type III secretion system (T3SS)-dependent translocation of S. enterica can be deployed for delivery of heterologous antigens to antigen-presenting cells. Here we investigated the efficacy of various effector proteins of the Salmonella pathogenicity island (SPI2)-encoded T3SS for the translocation of model antigens and elicitation of immune responses. The SPI2 T3SS effector proteins SifA, SteC, SseL, SseJ, and SseF share an endosomal membrane-associated subcellular localization after translocation. We observed that all effector proteins could be used to translocate fusion proteins with the model antigens ovalbumin and listeriolysin into the cytosol of host cells. Under in vitro conditions, fusion proteins with SseJ and SteC stimulated T-cell responses that were superior to those triggered by fusion proteins with SseF. However, in mice vaccinated with Salmonella carrier strains, only fusion proteins based on SseJ or SifA elicited potent T-cell responses. These data demonstrate that the selection of an optimal SPI2 effector protein for T3SS-mediated translocation is a critical parameter for the rational design of effective Salmonella-based recombinant vaccines.
authors.affiliation: Mikrobiologisches Institut, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Wael Abdel Halim
authors.initials: WA
authors.lastname: Hegazy
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Leonid
authors.initials: L
authors.lastname: Metelitsa
authors.forename: Michael
authors.initials: M
authors.lastname: Hensel
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022562:Salmonella Vaccines / Q000235:genetics / Q000276:immunology; D019779:Salmonella enterica / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D001427:Bacterial Toxins; D004337:Drug Carriers; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D011993:Recombinant Fusion Proteins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D010047:Ovalbumin; C038705:hlyA protein, Listeria monocytogenes