title: 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.
abstract: 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.
authors.affiliation: IRIS, Chiron Vaccines Immunobiological Research Institute Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Marchetti
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.forename: V
authors.initials: V
authors.lastname: Giannelli
authors.forename: M M
authors.initials: MM
authors.lastname: Giuliani
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: S
authors.initials: S
authors.lastname: Censini
authors.forename: A
authors.initials: A
authors.lastname: Covacci
authors.forename: P
authors.initials: P
authors.lastname: Massari
authors.forename: C
authors.initials: C
authors.lastname: Pagliaccia
authors.forename: R
authors.initials: R
authors.lastname: Manetti
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
authors.forename: G
authors.initials: G
authors.lastname: Douce
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: P
authors.initials: P
authors.lastname: Ghiara
mesh_terms: 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
chemical_list: 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