Immunization against natural Helicobacter pylori infection in nonhuman primates.
Helicobacter pylori infection is widespread in some breeding groups of a rhesus monkey colony (71% H. pylori positive by 1 year), and the rate of seroconversion is also high. As a result, these groups can be used to test the safety and efficacy of an anti-H. pylori vaccine. Nine-month-old female animals were randomized to receive either 8 mg of recombinant urease (rUre) plus 25 microg of Escherichia coli heat-labile enterotoxin (LT) (n = 26) or placebo plus LT (n = 29), given four times at 1-week intervals followed by a booster 1 month later. Ten months after the start of the immunization, the animals were subjected to endoscopy and biopsy samples were obtained. H. pylori negativity was defined as no H. pylori growth by culture and no H. pylori observed at histology. By this criterion, 2 (7%) of 29 animals receiving placebo and 8 (31%) of 26 immunized animals were H. pylori negative (P < 0.035). In addition, antral gastritis score was significantly less in H. pylori-negative immunized monkeys than in H. pylori-positive animals, whether they were given rUre plus LT or placebo plus LT (P < 0.02 or P < 0.01, respectively). Interestingly, antral gastritis was also significantly less in H. pylori-positive animals given rUre plus LT than in H. pylori-positive animals given placebo plus LT (P < 0.02). However, quantitative cultures did not demonstrate significant differences between the two latter groups. It is concluded that oral administration of rUre vaccine plus LT significantly protects nonhuman primates against H. pylori infection while not causing undesirable side effects.
Laboratory of Gastrointestinal and Liver Studies, Digestive Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. ADUBOIS@USUHS.MIL
A
A
Dubois
C K
CK
Lee
N
N
Fiala
H
H
Kleanthous
P T
PT
Mehlman
T
T
Monath
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D004724:Endoscopy; D004768:Enterotoxins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D008253:Macaca mulatta; D011323:Primates; D012463:Saliva / Q000276:immunology; D014510:Urease / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli; D014510:Urease