Oral immunization with recombinant Helicobacter pylori urease confers long-lasting immunity against Helicobacter felis infection.
Recombinant Helicobacter pylori urease (rUre) has been shown to confer protection against challenge with Helicobacter felis in mice. The purpose of the present study was to examine duration of the immune response and long-term protective efficacy of immunization with rUre. Swiss Webster mice were orally immunized four times at weekly intervals with 100 microg rUre plus 5 microg heat-labile enterotoxin of Escherichia coli (LT) adjuvant, or with LT only. At 4, 10, 20 or 40 weeks post immunization, 25 rUre-immunized mice and control mice were challenged with H. felis and sacrificed at 2 or 10 weeks post-challenge. H. felis infection was assessed by gastric urease assay and by histology. Anti-H. pylori urease specific antibody levels were measured in serum and saliva both pre- and post-challenge. Over the 40 week time period, the infection rates in rUre-immunized mice were significantly lower than those in controls (p < 0.05) as assessed by gastric urease activity. Protection ranged from 79 100% at 2 weeks post-challenge and 63-78% at 10 weeks post-challenge. Gastric bacterial density in rUre-immunized mice was significantly lower than that of controls (p < 0.03) as determined by histologic assessment. Anti-urease antibody levels remained elevated in the serum and mucosal compartments at 39 weeks following immunization. This study shows that immunization with rUre plus LT results in long-lasting protective immunity against challenge with H. felis.
Myers
G A
GA
Oravax Inc., Cambridge, MA 02139, USA. gmyers@oravax.com
Ermak
T H
TH
Georgakopoulos
K
K
Tibbitts
T
T
Ingrassia
J
J
Gray
H
H
Kleanthous
H
H
Lee
C K
CK
Monath
T P
TP
D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology*; D004768:Enterotoxins; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005260:Female; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology*; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D013270:Stomach / Q000201:enzymology / Q000382:microbiology; D014510:Urease / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; C027538:heat-labile enterotoxin, E coli; D014510:Urease