title: Protection against murine listeriosis by oral vaccination with recombinant Salmonella expressing hybrid Yersinia type III proteins.
abstract: In the present study, we have investigated the possibility to engage the Yersinia outer protein E (YopE) as a carrier molecule for heterologous Ag delivery by the type III secretion system of Salmonella typhimurium. Defined secretion and translocation domains of YopE were fused to the immunodominant T cell Ags listeriolysin O and p60 of Listeria monocytogenes. In vitro experiments showed that S. typhimurium allows secretion and translocation of large hybrid YopE proteins in a type III-dependent fashion. Translocation and cytosolic delivery of these chimeric proteins into host cells, but not secretion into endosomal compartments, led to efficient MHC class I-restricted Ag presentation of listerial nonamer peptides. Mice orally vaccinated with a single dose of attenuated S. typhimurium expressing translocated hybrid YopE proteins revealed high numbers of IFN-gamma-producing cells reactive with listeriolysin O 91-99 or p60 217-225, respectively. This CD8 T cell response protected mice against a challenge with L. monocytogenes. In conclusion, these findings suggest that YopE is a versatile carrier molecule for type III-mediated foreign Ag delivery by Salmonella vaccine strains.
authors: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität München, München, Germany. ruessmann@m3401.mpk.med.uni-muenchen.de
authors: H
authors: H
authors: Rüssmann
authors: E I
authors: EI
authors: Igwe
authors: J
authors: J
authors: Sauer
authors: W D
authors: WD
authors: Hardt
authors: A
authors: A
authors: Bubert
authors: G
authors: G
authors: Geginat
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins; D003600:Cytosol / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007941:Leukemia P388 / Q000276:immunology / Q000382:microbiology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000378:metabolism; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D015007:Yersinia / Q000235:genetics* / Q000276:immunology*
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins; D022562:Salmonella Vaccines; D014614:Vaccines, Synthetic; C063239:yopE protein, Yersinia; C038705:hlyA protein, Listeria monocytogenes