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Infection and Immunity, June 2001, p. 3581-3590, Vol. 69, No. 6
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.6.3581-3590.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Safety and Immunogenicity of Oral Inactivated Whole-Cell
Helicobacter pylori Vaccine with Adjuvant among
Volunteers with or without Subclinical Infection
Karen L.
Kotloff,1,2,*
Marcelo B.
Sztein,1,2
Steven S.
Wasserman,2
Genevieve A.
Losonsky,1,2
Susan C.
DiLorenzo,1 and
Richard I.
Walker3,
Division of Infectious Disease and Tropical
Pediatrics, Department of Pediatrics,1 and
Division of Geographic Medicine, Department of
Medicine,2 Center for Vaccine
Development, University of Maryland School of Medicine, Baltimore,
and Antex Biologics, Inc., Gaithersburg,3
Maryland
Received 3 November 2000/Returned for modification 21 December
2000/Accepted 25 February 2001
Helicobacter pylori infection of the gastric mucosa can
be found in approximately 50% of the world's population and is
associated with a range of pathology, including peptic ulcer, atrophic
gastritis, and gastric cancer. To explore immunization as a strategy
for preventing and treating H. pylori-associated
disease, we assessed the safety and immunogenicity in healthy adults of
a formalin-inactivated, oral H. pylori whole-cell
(HWC) vaccine, administered with or without mutant Escherichia
coli heat-labile toxin (LTR192G) as a mucosal
adjuvant. In a dose-response study, 23 subjects with or without
H. pylori infection were vaccinated with either 2.5 × 106 HWC, 2.5 × 108 HWC, or 2.5 × 1010 HWC, plus 25 µg of LTR192G.
Thereafter, a randomized study was conducted in which 18 H. pylori-infected subjects were assigned, in a double-blind
fashion, to receive either 2.5 × 1010 HWC plus
placebo-adjuvant, placebo-vaccine plus 25 µg of
LTR192G, placebo-vaccine plus placebo-adjuvant, or
2.5 × 1010 HWC plus 25 µg of
LTR192G. Diarrhea (six subjects), low-grade fever (five
subjects), and vomiting (two subjects) were observed, usually after the
first dose. Significant rises in geometric mean mucosal (fecal and
salivary) anti-HWC immunoglobulin A antibodies occurred among
H. pylori-infected and uninfected subjects following inoculation with 2.5 × 1010 HWC plus 25 µg of
LTR192G. Moreover, among H. pylori-negative volunteers, this regimen induced significant
lymphoproliferative responses in 5 of 10 subjects and gamma interferon
production responses to H. pylori sonicate in 7 of 10 subjects. There was no evidence that vaccination eradicated
H. pylori in infected volunteers. These results
suggest that it is possible to stimulate mucosal and systemic immune
responses in humans to H. pylori antigens by using an
HWC vaccine.
*
Corresponding author. Mailing address: University of
Maryland School of Medicine, Center for Vaccine Development, 685 West Baltimore St., HSF 480, Baltimore, MD 21201. Phone: (410) 706-5328. Fax: (410) 706-6205. E-mail:
kkotloff{at}medicine.umaryland.edu.

Present address: Division of Bacterial, Parasitic, and Allergenic
Products, Center for Biologics Evaluation and Research,
U.S. Food
and Drug Administration, Washington, D.C.
Infection and Immunity, June 2001, p. 3581-3590, Vol. 69, No. 6
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.6.3581-3590.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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