title: Intranasal immunization strategy to impede pilin-mediated binding of Pseudomonas aeruginosa to airway epithelial cells.
abstract: Prevention of pulmonary Pseudomonas aeruginosa infections represents a critical unmet medical need for cystic fibrosis (CF) patients. We have examined the tenet that a mucosal immunization approach can reduce interactions of a piliated form of this opportunistic pathogen with respiratory epithelial cells. Vaccinations were performed using ntPEpilinPAK, a protein chimera composed of a nontoxic form of P. aeruginosa exotoxin A (ntPE), where the C-terminal loop amino acid sequence of the PAK strain pilin protein was inserted in place of the ntPE Ib domain. Intranasal (i.n.) immunization of BALB/c mice with ntPEpilinPAK generated both serum and saliva immune responses. A series of in vitro studies showed that diluted samples of saliva obtained from immunized mice reduced pilin-dependent P. aeruginosa binding to polarized human tracheal epithelial cells, protected human pulmonary epithelial cells from cytotoxic actions associated with bacterial challenge, and reduced exotoxin A toxicity. Overall, i.n. administration of ntPEpilinPAK induced mucosal and systemic immune responses that may be beneficial for blocking early stage adhesion and/or infection events of epithelial cell-P. aeruginosa interactions at oropharyngeal surfaces.
authors.affiliation: Trinity BioSystems, Inc., 1455 Adams Dr., Suite 1317, Menlo Park, CA 94025-1438, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Hsieh
authors.forename: Doris M
authors.initials: DM
authors.lastname: Tham
authors.forename: Weijun
authors.initials: W
authors.lastname: Feng
authors.forename: Fan
authors.initials: F
authors.lastname: Huang
authors.forename: Selamawit
authors.initials: S
authors.lastname: Embaie
authors.forename: Keyi
authors.initials: K
authors.lastname: Liu
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
authors.forename: Ralf
authors.initials: R
authors.lastname: Hertle
authors.forename: David J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Mrsny
mesh_terms: D036002:ADP Ribose Transferases / Q000008:administration & dosage / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology*; D005098:Exotoxins / Q000008:administration & dosage / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000502:physiology*; D006790:Host-Parasite Interactions; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D012463:Saliva / Q000276:immunology; D014611:Vaccination; D037521:Virulence Factors / Q000008:administration & dosage / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A