Protection against Helicobacter pylori infection in mice by intragastric vaccination with H. pylori antigens is achieved using a non-toxic mutant of E. coli heat-labile enterotoxin (LT) as adjuvant.
We have previously shown that infection of mice with H. pylori can be prevented by oral immunization with H. pylori antigens given together with E. coli heat-labile enterotoxin (LT) as adjuvant. Since LT cannot be used in humans because of its unacceptable toxicity, we investigated whether protection of mice could be achieved by co-administration of antigens with non-toxic LT mutants. Here we show that CD1/SPF mice are protected against infection after oral vaccination with either purified H. pylori antigens (native and recombinant VacA, urease and CagA), or whole-cell vaccine formulations, given together with the non-toxic mutant LTK63 as a mucosal adjuvant. Furthermore we show that such protection is antigen-specific since immunization with recombinant or native VacA plus LTK63 conferred protection against infection by an H. pylori Type I strain, which expresses VacA, but not against challenge with a Type II strain which is not able to express this antigen. These results show that: (1) protection against H. pylori can be achieved in the mouse model of infection using subunit recombinant constructs plus non-toxic mucosal adjuvants; and (2) this mouse model is an useful tool in testing H. pylori vaccine formulations for eventual use in humans.
Marchetti
M
M
IRIS, Chiron Vaccines Immunobiological Research Institute Siena, Italy.
Rossi
M
M
Giannelli
V
V
Giuliani
M M
MM
Pizza
M
M
Censini
S
S
Covacci
A
A
Massari
P
P
Pagliaccia
C
C
Manetti
R
R
Telford
J L
JL
Douce
G
G
Dougan
G
G
Rappuoli
R
R
Ghiara
P
P
D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D008297:Male; D051379:Mice; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli