Objectif * To produce a genetically detoxified H. pylori cytotoxin protein suitable for evaluation as a vaccine candidate.* To assess the genetic variability of Chinese isolates of H. pylori, and to evaluate the relationship of this variability to the incidence of severe disease.* To test in the mouse model, vaccine candidates which show promise in protecting against European strains of H. pylori for their capacity to induce protection against infection by virulent Chinese strains.Expected Outcome* Identification of biologically relevant regions of the VacA protein.* A genetically detoxified and antigenically intact cytotoxin molecule as a vaccine candidate.* Serological data on the association of infection with Type I, VacA and CagA expressing strains with gastroduodenal disease in China.* Genotypic and phenotypic data on the variation of H. pylori strains in clinical isolates form Chinese patients and their assocation with disease.* Pathogenicity in vivo and in vitro of clinical isolates from China related to their genotype and phenotype.* Evaluation of the cytotoxin toxoids in conferring protective immunity against infection by European and Chinese strains of H. pylori.* A bank of monclonal antibodies raised against purified native toxin wil be screened for their ability to neutralize purified toxin.* Sequences coding for potentially non-toxic VacA proteins willl be created in E. coli by site directed mutagensis. Mutated genes constructed in E. coli will be transferred into H. pylori.* Mutated toxin proteins will be tested for their ability to induce gastric lesions after oral administration to mice.* Sera from Chinese patients undergoing routine endoscopy will be analysed for their ability to recognize CagA, VacA and other H. pylori antigens to ascertain any correlation with particular conditions such as duodenal ulcer and gastric cancer.* Strains isolated by endoscopy from Chinese patients will be analysed for the presence of the CagA genotype and by immunoblot for expression of CagA and VacA proteins.* Selected isolated of different genotype and phenotype will be adapted to mice by sequential passage.* Non-toxic VacA proteins will be tested for their ability to protect mice from infection with European and Chinese strains of H. pylori adapted to colonization of mice. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesclinical medicineoncology Programme(s) FP4-INCO - Specific research, technological development and demonstration programme in the field of cooperation with third countries and international organizations, 1994-1998 Thème(s) 01 - SCIENTIFIC AND TECHNOLOGICAL COOPERATION IN EUROPE AND WITH INTERNATIONAL ORGANIZATIONS Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur CHIRON S.R.L. Contribution de l’UE Aucune donnée Adresse VIA FIORENTINA 1 53100 SIENA Italie Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée Participants (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire SECOND MILITARY MEDICAL UNIVERSITY Chine Contribution de l’UE Aucune donnée Adresse 174,Changhai Road 174 Changhai Hospital 200433 SHANGHAI Voir sur la carte Coût total Aucune donnée UNIVERSITY OF LEEDS Royaume-Uni Contribution de l’UE Aucune donnée Adresse St. James's University Clinical Sciences Building LS9 7TF LEEDS Voir sur la carte Coût total Aucune donnée