Improvement of the live vaccine strain Salmonella enterica serovar Typhi Ty21a for antigen delivery via the hemolysin secretion system of Escherichia coli.
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.
Hotz
Christian
C
Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Würzburg, Germany. christian.hotz@mail.uni-wuerzburg.de
Fensterle
Joachim
J
Goebel
Werner
W
Meyer
Susanne R
SR
Kirchgraber
Gabriel
G
Heisig
Martin
M
Fürer
Andreas
A
Dietrich
Guido
G
Rapp
Ulf R
UR
Gentschev
Ivaylo
I
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
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