Safety and immunogenicity of oral inactivated whole-cell Helicobacter pylori vaccine with adjuvant among volunteers with or without subclinical infection

Helicobacter pylori infection of the gastric mucosa can be found in approxi mately 50% of the world's population and is associated with a range of path ology, including peptic ulcer, atrophic gastritis, and gastric cancer. To e xplore immunization as a strategy for preventing and treating H. pylori-ass ociated disease, we assessed the safety and immunogenicity in healthy adult s of a formalin-inactivated, oral H. pylori whole-cell (HWC) vaccine, admin istered with or without mutant Escherichia coli heat-labile toxin (LTR192G) as a mucosal adjuvant. In a dose-response study, 23 subjects with or witho ut N. pylori infection were vaccinated with either 2.5 x 10(6) HWC, 2.5 x 1 0(8) HWC, or 2.5 x 10(10) HWC, plus 25 mug of LTR192G. Thereafter, a random ized study was conducted in which 18 H. pylori-infected subjects were assig ned, in a double-blind fashion, to receive either 2.5 x 10(10) HWC plus pla cebo-adjuvant, placebo-vaccine plus 25 mug of LTR192G, placebo-vaccine plus placebo-adjuvant, or 2.5 x 10(10) HWC plus 25 mug of LTR192G. Diarrhea (si x subjects), low-grade fever (five subjects), and vomiting (two subjects) w ere observed, usually after the first dose. Significant rises in geometric mean mucosal (fecal and salivary) anti-HWC immunoglobulin A antibodies occu rred among H. pylori-infected and uninfected subjects following inoculation with 2.5 x 10(10) HWC plus 25 mug of LTR192G. Moreover, among H. pylori-ne gative volunteers, this regimen induced significant lymphoproliferative res ponses 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 t o H. pylori antigens by using an HWC vaccine.