Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.
OBJECTIVE
Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults.


METHODS
Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures.


RESULTS
Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density.


CONCLUSIONS
H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.
Michetti
P
P
Division of Gastroenterology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland. pmichett@bidmc.harvard.edu
Kreiss
C
C
Kotloff
K L
KL
Porta
N
N
Blanco
J L
JL
Bachmann
D
D
Herranz
M
M
Saldinger
P F
PF
Corthésy-Theulaz
I
I
Losonsky
G
G
Nichols
R
R
Simon
J
J
Stolte
M
M
Ackerman
S
S
Monath
T P
TP
Blum
A L
AL
D000284:Administration, Oral; D000328:Adult; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins; D005260:Female; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000009:adverse effects; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D008875:Middle Aged; D013270:Stomach / Q000382:microbiology; D014510:Urease / Q000276:immunology*
D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; C027538:heat-labile enterotoxin, E coli; D014510:Urease