title: Pre-existing anti-Salmonella vector immunity prevents the development of protective antigen-specific CD8 T-cell frequencies against murine listeriosis.
abstract: Our laboratory has focused its research on the use of the type III secretion system of Salmonella enterica serovar Typhimurium to translocate heterologous antigens directly into the cytosol of antigen-presenting cells. We have previously reported that the single oral immunization of mice with a recombinant Salmonella aroA/sptP mutant strain expressing the translocated Yersinia outer protein E fused to the immunodominant antigen p60 from Listeria monocytogenes in a type III-mediated fashion results in the efficient induction of p60-specific CD8 T cells and confers protection against a lethal Listeria challenge infection. In the present study, we determined whether pre-existing anti-Salmonella vector immunity influences the induction of p60-specific CD8 T cells and modulates protective immunity against listeriosis after oral vaccination with recombinant Salmonella. After single oral immunization, the Salmonella aroA/sptP double mutant strain was found to colonize spleens of mice for 21days. In contrast, the period of colonization was significantly shortened to 6days due to anti-Salmonella vector immunity after second oral immunization. The latter scenario led to the induction of low-level frequencies of antigen-specific CD8 T cells. Compared to the significantly higher numbers of p60-specific T lymphocytes elicited after single oral immunization, the low amount of Listeria-specific CD8 T cells did not confer protection against listeriosis.
authors.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 9a, 80336 Munich, Bavaria, Germany.
authors.forename: Victòria E
authors.initials: VE
authors.lastname: Sevil Domènech
authors.forename: Klaus
authors.initials: K
authors.lastname: Panthel
authors.forename: Katrin M
authors.initials: KM
authors.lastname: Meinel
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Holger
authors.initials: H
authors.lastname: Rüssmann
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011993:Recombinant Fusion Proteins