Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys.
Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 microg Escherichia coli heat-labile enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered over an 8 week period. All five vaccinated monkeys had a greater than two-fold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori colonization. H. pylori was eradicated from these monkeys with a course of antimicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H. pylori. Necropsy was performed 23 weeks after rechallenge and H. pylori colonization was determined by histological examination of 12 individual gastric sites. A significant reduction in colonization (p < or = 0.0001; Friedman's analysis of variance) was found in the vaccinated animals. Histopathologic examination of necropsy tissues also revealed a trend towards reduced gastritis and epithelial alterations in the vaccinated group compared to animals receiving LT alone. This study provides the first evidence for effective vaccination of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gastric inflammation.
Lee
C K
CK
OraVax, Inc., Cambridge, MA, USA. clee@oravax.com
Soike
K
K
Hill
J
J
Georgakopoulos
K
K
Tibbitts
T
T
Ingrassia
J
J
Gray
H
H
Boden
J
J
Kleanthous
H
H
Giannasca
P
P
Ermak
T
T
Weltzin
R
R
Blanchard
J
J
Monath
T P
TP
D000276:Adjuvants, Immunologic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D001729:Bismuth / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004768:Enterotoxins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D029968:Escherichia coli Proteins; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000254:growth & development; D008253:Macaca mulatta; D008795:Metronidazole / Q000627:therapeutic use; D009853:Omeprazole / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000276:immunology; D012459:Salicylates / Q000627:therapeutic use; D012463:Saliva / Q000276:immunology; D014510:Urease / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D009942:Organometallic Compounds; D011994:Recombinant Proteins; D012459:Salicylates; D008795:Metronidazole; C015715:bismuth subsalicylate; C027538:heat-labile enterotoxin, E coli; D014510:Urease; D017291:Clarithromycin; D009853:Omeprazole; D001729:Bismuth