title: Encapsulation of Cwp84 into pectin beads for oral vaccination against Clostridium difficile.
abstract: We have designed an oral vaccine against Clostridium difficile infection. The virulent factor Cwp84, that is a cystein protease highly immunogenic in patients with C. difficile-associated disease, was entrapped within pectin beads. Beads encapsulating Cwp84 were shown to be stable in the simulated intestinal medium and to release the cystein protease once in the simulated colonic medium. Three groups of hamsters were immunized, the first receiving pectin beads encapsulating Cwp84, the second unloaded beads and the third one free Cwp84. After three immunizations by the intragastric route, all groups received clindamycine. Post-challenge survival with a strain of C. difficile showed that 2 days after infection, all hamsters treated with unloaded beads and all hamsters treated with free Cwp84 have deceased after 7 days, whereas about 40% of hamsters administered with Cwp84-loaded beads survived 10 days after challenge, proving that oral vaccination provides partial protection. These first data obtained with an oral vaccine against C. difficile appear promising for preventing this infection.
authors.affiliation: Univ Paris-Sud, UMR CNRS 8612, IPSIT, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sandolo
authors.forename: Séverine
authors.initials: S
authors.lastname: Péchiné
authors.forename: Alban
authors.initials: A
authors.lastname: Le Monnier
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoys
authors.forename: Claire
authors.initials: C
authors.lastname: Janoir
authors.forename: Tommasina
authors.initials: T
authors.lastname: Coviello
authors.forename: Franco
authors.initials: F
authors.lastname: Alhaique
authors.forename: Anne
authors.initials: A
authors.lastname: Collignon
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D016360:Clostridioides difficile / Q000201:enzymology / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology / Q000517:prevention & control*; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008970:Molecular Weight; D010368:Pectins / Q000737:chemistry*; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004337:Drug Carriers; D007074:Immunoglobulin G; D010368:Pectins; C524258:Cwp84 protein, Clostridium difficile; D003546:Cysteine Endopeptidases