Antibody responses to Yersinia pestis F1-antigen expressed in Salmonella typhimurium aroA from in vivo-inducible promoters.
Attenuated mutants of Salmonella typhimurium are being evaluated as delivery systems for a variety of heterologous vaccine antigens. Gene promoters which are induced in vivo can direct the stable expression of genes encoding these antigens. We have investigated the utility of the phoP, ompC, pagC and lacZ gene promoters for expression of the Y. pestis F1-antigen in S. typhimurium SL3261 (aroA). After i.g. (intragastric) dosing the highest level of spleen colonisation was found with recombinant Salmonella expressing F1-antigen from the phoP gene promoter, and this recombinant was most effective in inducing serum and mucosal antibody responses. The use of the pagC gene promoter to direct expression of F1-antigen resulted in the induction of serum and mucosal antibody responses even though the recombinant Salmonella were unable to colonise spleen tissues suggesting that colonisation of these tissues is not essential for the induction of antibody responses.
Bullifent
H L
HL
Defence Evaluation and Research Agency, CBD Porton Down, Salisbury, UK.
Griffin
K F
KF
Jones
S M
SM
Yates
A
A
Harrington
L
L
Titball
R W
RW
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli; D015964:Gene Expression Regulation, Bacterial; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; C086725:caf1 protein, Yersinia pestis