title: Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis.
abstract: Vaccination provides the most potent measure against infectious disease, and recombinant (r) viable vaccines expressing defined pathogen-derived antigens represent powerful candidates for future vaccination strategies. In a new approach we constructed r-aroA- Salmonella typhimurium displaying p60 or listeriolysin (Hly) antigen of Listeria monocytogenes in secreted or somatic form in the host cell. Vaccination of mice with r-aroA- S. typhimurium induced protection against the intracellular pathogen L. monocytogenes only with secreted and not with somatic antigen. Secreted Hly was slightly more potent in inducing protective immunity than secreted p60. Both r-aroA- S. typhimurium secreting p60 in the endosome and r-aroA- S. typhimurium secreting Hly in the cytosol induced protective CD4+ and CD8+ T-cells suggesting CD8+ T-cell stimulation independent from intracellular residence of r-aroA- S. typhimurium carriers. Hence, not only the type of antigen but also its display by the r-carrier within the host cell critically influences vaccine efficacy.
authors.affiliation: Department of Immunology, University of Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hess
authors.forename: I
authors.initials: I
authors.lastname: Gentschev
authors.forename: D
authors.initials: D
authors.lastname: Miko
authors.forename: M
authors.initials: M
authors.lastname: Welzel
authors.forename: C
authors.initials: C
authors.lastname: Ladel
authors.forename: W
authors.initials: W
authors.lastname: Goebel
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C038705:hlyA protein, Listeria monocytogenes