Safety and Immunogenicity of Oral Inactivated Whole-Cell Helicobacter pylori Vaccine with Adjuvant among Volunteers with or without Subclinical Infection

Abstract

Helicobacter pylori infection of the gastric mucosa can be found in approximately 50% of the world9s 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 (LT_R192G) as a mucosal adjuvant. In a dose-response study, 23 subjects with or withoutH. pylori infection were vaccinated with either 2.5 × 10⁶ HWC, 2.5 × 10⁸ HWC, or 2.5 × 10¹⁰ HWC, plus 25 μg of LT_R192G. 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 LT_R192G, placebo-vaccine plus placebo-adjuvant, or 2.5 × 10¹⁰ HWC plus 25 μg of LT_R192G. 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 amongH. pylori-infected and uninfected subjects following inoculation with 2.5 × 10¹⁰ HWC plus 25 μg of LT_R192G. 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 eradicatedH. 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.