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Infection and Immunity, September 1998, p. 4340-4346, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Immunization against Natural Helicobacter
pylori Infection in Nonhuman Primates
Andre
Dubois,1,*
Cynthia K.
Lee,2
Nancy
Fiala,1
Harry
Kleanthous,2
Patrick T.
Mehlman,1 and
Thomas
Monath2
Laboratory of Gastrointestinal and Liver
Studies, Digestive Diseases Division, Department of Medicine,
Uniformed Services University of the Health Sciences, Bethesda,
Maryland,1 and
OraVax, Inc., Cambridge,
Massachusetts2
Received 12 January 1998/Returned for modification 24 April
1998/Accepted 8 June 1998
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 µg 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.
*
Corresponding author. Mailing address: Department of
Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. Phone: (301) 295-3607. Fax:
(301) 295-3676 or -3557. E-mail: ADUBOIS{at}USUHS.MIL.
Infection and Immunity, September 1998, p. 4340-4346, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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