title: Secretion of different listeriolysin cognates by recombinant attenuated Salmonella typhimurium: superior efficacy of haemolytic over non-haemolytic constructs after oral vaccination.
abstract: Viable antigen (Ag) delivery systems expressing defined pathogen-derived proteins represent powerful candidates for future vaccination strategies. Here, recombinant (r)Salmonella typhimurium aroA strains secreting listeriolysin (Hly) of Listeria monocytogenes in haemolytic or non-haemolytic form were constructed to direct these carriers into cytosolic or phagosomal host cell compartments, respectively. Oral and intravenous (i.v.) vaccination of mice with either construct induced 'transporter associated with antigen processing'-dependent protection against the intracellular bacterial pathogen L. monocytogenes. Comparison of oral immunization with both rSalmonella constructs revealed superior vaccine efficacy of the haemolytic rS. typhimurium Hlys construct as compared to the non-haemolytic rSalmonella Hlys(492) strain. In contrast, efficacy of i.v. vaccination with either rSalmonella strain did not significantly differ. Therefore, rSalmonella strains secreting biologically active Hly represent valuable delivery systems for heterologous rAg or DNA which should be exploited for future mucosal vaccination strategies.
authors.affiliation: Max-Planck-Institute for Infection Biology, Department of Immunology, D-10117, Berlin, Germany. hess@november.de
authors.forename: J
authors.initials: J
authors.lastname: Hess
authors.forename: L
authors.initials: L
authors.lastname: Grode
authors.forename: I
authors.initials: I
authors.lastname: Gentschev
authors.forename: J
authors.initials: J
authors.lastname: Fensterle
authors.forename: G
authors.initials: G
authors.lastname: Dietrich
authors.forename: W
authors.initials: W
authors.lastname: Goebel
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000008:administration & dosage; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006460:Hemolysin Proteins; D006461:Hemolysis; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000008:administration & dosage
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C038705:hlyA protein, Listeria monocytogenes