title: 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 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 (LT(R192G)) as a mucosal adjuvant. In a dose-response study, 23 subjects with or without H. pylori infection were vaccinated with either 2.5 x 10(6) HWC, 2.5 x 10(8) HWC, or 2.5 x 10(10) HWC, plus 25 microg 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 x 10(10) HWC plus placebo-adjuvant, placebo-vaccine plus 25 microg of LT(R192G), placebo-vaccine plus placebo-adjuvant, or 2.5 x 10(10) HWC plus 25 microg 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 among H. pylori-infected and uninfected subjects following inoculation with 2.5 x 10(10) HWC plus 25 microg 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 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.
authors.affiliation: Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA. kkotloff@medicine.umaryland.edu
authors.forename: K L
authors.initials: KL
authors.lastname: Kotloff
authors.forename: M B
authors.initials: MB
authors.lastname: Sztein
authors.forename: S S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: G A
authors.initials: GA
authors.lastname: Losonsky
authors.forename: S C
authors.initials: SC
authors.lastname: DiLorenzo
authors.forename: R I
authors.initials: RI
authors.lastname: Walker
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004311:Double-Blind Method; D004768:Enterotoxins / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000166:cytology / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D015848:Interleukin-5; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli