Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers
Détails
ID Serval
serval:BIB_91556BE57D5A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers
Périodique
Gut
ISSN
0017-5749 (Print)
Statut éditorial
Publié
Date de publication
11/2002
Volume
51
Numéro
5
Pages
634-40
Notes
Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Résumé
BACKGROUND AND AIMS: Escherichia coli heat labile enterotoxin (LT) at doses of 5 micro g or 10 micro g has adjuvant activity for oral immunisation in humans infected with Helicobacter pylori, but causes severe diarrhoea. This study was undertaken to establish a safe and effective dose of LT, to confirm the safety of recombinant urease, and to compare the immunogenicity of orally compared with enterically delivered urease. METHODS: 42 healthy adults without present or past H pylori infection were randomised to receive 60 mg recombinant H pylori urease in soluble or in encapsulated form, given with doses of LT ranging from 0 micro g to 2.5 micro g. Four oral doses were administered at day 1, 8, 29, and 57. Specific IgG, IgA, and antibody secreting cells were measured as well as total alpha4beta7 integrin positive lymphocyte responses. RESULTS: Enterically delivered urease was well tolerated and no serious adverse events occurred. Mild diarrhoea (one to four loose stools) occurred after the first immunisation in 50% (6 of 12) of the volunteers exposed to 2.5 micro g LT (p=0.06; paired t test, compared with baseline) but not in volunteers exposed to lower LT doses. Immune responses occurred in five (p=0.048; Fisher's exact test), one, two, and one of six subjects exposed to 2.5 micro g, 0.5 micro g, 0.1 micro g, and no LT, respectively. Significant CD4(+), CD69(+), and CD45RO(hi) responses occurred over time among alpha4beta7(hi) lymphocytes in volunteers receiving 2.5 micro g LT. Enterically delivered urease induced higher lymphocyte responses than soluble urease. CONCLUSIONS: The safety of H pylori urease is confirmed. Oral LT may conserve its adjuvant activity at low doses with minimal side effects.
Mots-clé
Adjuvants, Immunologic/*administration & dosage
Administration, Oral
Adult
Analysis of Variance
Bacterial Toxins/*administration & dosage
Delayed-Action Preparations
Diarrhea/etiology
Double-Blind Method
Enterotoxins/*administration & dosage
*Escherichia coli Proteins
Female
Helicobacter Infections/*prevention & control
Helicobacter pylori/*enzymology
Humans
Male
Middle Aged
Statistics, Nonparametric
T-Lymphocytes/immunology
Urease/*administration & dosage/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 17:02
Dernière modification de la notice
20/08/2019 15:54