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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,dagger

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.

dagger 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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