title: Concomitant cytosolic delivery of two immunodominant listerial antigens by Salmonella enterica serovar typhimurium confers superior protection against murine listeriosis.
abstract: During its interaction with host cells, Salmonella enterica serovar Typhimurium employs a type III secretion system for cytosolic targeting of virulence factors. This protein translocation mechanism is a useful tool for heterologous antigen delivery by attenuated Salmonella vaccine carrier strains. In the present study, we used the Yersinia outer protein E (YopE) as a carrier molecule for Salmonella type III-dependent cytosolic delivery of the immunodominant CD8 T-cell antigens listeriolysin O (LLO) and p60 of Listeria monocytogenes. It is shown that concomitant translocation of hybrid YopE/LLO and YopE/p60 proteins by Salmonella led to antigen presentation and CD8 T-cell priming efficacies comparable to those of translocation of single listerial antigens. However, simultaneous translocation of LLO and p60 significantly surpassed single cytosolic antigen delivery in the ability to protect against Listeria. For the first time, this study demonstrates that concomitant expression of two independent antigens via the same recombinant plasmid leads to superior protection against a challenge with an intracellular bacterial pathogen. In conclusion, these findings emphasize the versatility of Salmonella type III-mediated heterologous antigen delivery for the induction of cytotoxic T-lymphocyte-mediated immunity.
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität München, Germany.
authors.forename: Emeka I
authors.initials: EI
authors.lastname: Igwe
authors.forename: Gernot
authors.initials: G
authors.lastname: Geginat
authors.forename: Holger
authors.initials: H
authors.lastname: Rüssmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003600:Cytosol / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000517:prevention & control*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D016056:Immunodominant Epitopes; D011993:Recombinant Fusion Proteins; C063239:yopE protein, Yersinia; C038705:hlyA protein, Listeria monocytogenes