| Autor: |
Hsieh, Jennifer C., Tham, Doris M., Feng, Weijun, Huang, Fan, Embaie, Selamawit, Liu, Keyi, Dean, Deborah, Hertle, Ralf, FitzGerald, David J., Mrsny, Randall J. |
| Zdroj: |
Infection and Immunity; November 2005, Vol. 73 Issue: 11 p7705-7717, 13p |
| Abstrakt: |
ABSTRACTPrevention of pulmonary Pseudomonas aeruginosainfections 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. aeruginosaexotoxin 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. aeruginosabinding 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. aeruginosainteractions at oropharyngeal surfaces. |
| Databáze: |
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