title: Improvement of the live vaccine strain Salmonella enterica serovar Typhi Ty21a for antigen delivery via the hemolysin secretion system of Escherichia coli.
abstract: The attenuated Salmonella enterica serovar Typhi strain Ty21a (Ty21a) is the only attenuated live oral vaccine against typhoid fever. Ty21a is also an attractive carrier for the delivery of heterologous antigens. We have used Ty21a for antigen delivery via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of the type I secretion system (T1SS). In this study, we identified by genetic complementation that the specific mutation of rpoS correlated with the hemolysin production of strain Ty21a. We furthermore showed that complementation with a plasmid encoding rfaH, which is described to be a downstream target of rpoS, led to increased expression and secretion of hemolysin. Finally, we demonstrated a significant enhancement of antibody responses against the heterologous HlyA antigen of Ty21a after immunization of mice with rfaH complemented S. typhi strain secreting HlyA compared with the same strain without rfaH plasmid.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Würzburg, Germany. christian.hotz@mail.uni-wuerzburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Hotz
authors.forename: Joachim
authors.initials: J
authors.lastname: Fensterle
authors.forename: Werner
authors.initials: W
authors.lastname: Goebel
authors.forename: Susanne R
authors.initials: SR
authors.lastname: Meyer
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kirchgraber
authors.forename: Martin
authors.initials: M
authors.lastname: Heisig
authors.forename: Andreas
authors.initials: A
authors.lastname: Fürer
authors.forename: Guido
authors.initials: G
authors.lastname: Dietrich
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D001428:Bacterial Vaccines / Q000235:genetics* / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D005816:Genetic Complementation Test; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D012485:Salmonella typhi / Q000235:genetics* / Q000276:immunology*; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D010445:Peptide Elongation Factors; C106401:RfaH protein, E coli; D012808:Sigma Factor; D015534:Trans-Activators; D014613:Vaccines, Attenuated; C069567:sigma factor KatF protein, Bacteria