Safety and Immunogenicity of an Intramuscular Helicobacter pylori Vaccine in Noninfected Volunteers: A Phase I Study

Introduction: Helicobacter pylori infection is among the most common human infections and the major risk factor for peptic disease and gastric cancer. Immunization with vaccines containing the H pylori vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP), alone or in combination, have been shown to prevent experimental infection in animals. Aim: We sought to study the safety and immunogenicity of a vaccine consisting of recombinant VacA, CagA, and NAP given intramuscularly with aluminium hydroxide as an adjuvant to noninfected healthy subjects. Methods: This controlled, single-blind Phase I study randomized 57 H pylori-negative volunteers into 7 study arms exploring 2 dosages (10 and 25 μg) of each antigen and 3 schedules (0, 1, 2 weeks; 0, 1, 2 months; and 0, 1, 4 months) versus alum controls. All participants were followed for 5 months. Thirty-six subjects received a booster vaccination 18–24 months after the completion of the primary vaccination. Results: Local and systemic adverse reactions were mild and similar in placebo and vaccine recipients on the monthly schedules. All subjects responded to 1 or 2 of the antigens and 86% of all vaccines mounted immunoglobulin G antibody responses to all 3 antigens. Vaccinees exhibited an antigen-specific cellular response. Vaccination 18–24 months later elicited anamnestic antibody and cellular responses. Conclusions: This intramuscular H pylori vaccine demonstrated satisfactory safety and immunogenicity, produced antigen-specific T-cell memory, and, therefore, warrants further clinical study.

Abbreviations used in this paper: CagA, cytotoxin-associated antigen A, ELISA, enzyme-linked immunosorbent assay, GMT, geometric mean titer, HP3, H pylori vaccine containing CagA, NAP, and VacA, IFN, interferon, IL, interleukin, LT, Escherichia coli heat-labile enterotoxin, NAP, neutrophil activating protein, PBMC, peripheral blood mononuclear cells, VacA, vacuolating cytotoxin A