title: Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: a phase I study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 microg) 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.
authors.affiliation: Otto-von-Guericke Universitaet, Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: Viola
authors.initials: V
authors.lastname: Schultze
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Timo
authors.initials: T
authors.lastname: Ulrichs
authors.forename: Deborah
authors.initials: D
authors.lastname: Novicki
authors.forename: Francesco
authors.initials: F
authors.lastname: Norelli
authors.forename: Mario
authors.initials: M
authors.lastname: Contorni
authors.forename: Samuele
authors.initials: S
authors.lastname: Peppoloni
authors.forename: Duccio
authors.initials: D
authors.lastname: Berti
authors.forename: Daniela
authors.initials: D
authors.lastname: Tornese
authors.forename: Jitendra
authors.initials: J
authors.lastname: Ganju
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palla
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Scharschmidt
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide; D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; C092412:neutrophil-activating protein A, Helicobacter pylori; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma