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Publication : Protective live oral brucellosis vaccines stimulate Th1 and th17 cell responses.

First Author  Clapp B Year  2011
Journal  Infect Immun Volume  79
Issue  10 Pages  4165-74
PubMed ID  21768283 Mgi Jnum  J:176029
Mgi Id  MGI:5288137 Doi  10.1128/IAI.05080-11
Citation  Clapp B, et al. (2011) Protective live oral brucellosis vaccines stimulate Th1 and th17 cell responses. Infect Immun 79(10):4165-74
abstractText  Zoonotic transmission of brucellosis often results from exposure to Brucella-infected livestock, feral animals, or wildlife or frequently via consumption of unpasteurized milk products or raw meat. Since natural infection of humans often occurs by the oral route, mucosal vaccination may offer a means to confer protection for both mucosal and systemic tissues. Significant efforts have focused on developing a live brucellosis vaccine, and deletion of the znuA gene involved in zinc transport has been found to attenuate Brucella abortus. A similar mutation has been adapted for Brucella melitensis and tested to determine whether oral administration of DeltaznuA B. melitensis can confer protection against nasal B. melitensis challenge. A single oral vaccination with DeltaznuA B. melitensis rapidly cleared from mice within 2 weeks and effectively protected mice upon nasal challenge with wild-type B. melitensis 16M. In 83% of the vaccinated mice, no detectable brucellae were found in their spleens, unlike with phosphate-buffered saline (PBS)-dosed mice, and vaccination also enhanced the clearance of brucellae from the lungs. Moreover, vaccinated gamma interferon-deficient (IFN-gamma(-/-)) mice also showed protection in both spleens and lungs, albeit protection that was not as effective as in immunocompetent mice. Although IFN-gamma, interleukin 17 (IL-17), and IL-22 were stimulated by these live vaccines, only RB51-mediated protection was codependent upon IL-17 in BALB/c mice. These data suggest that oral immunization with the live, attenuated DeltaznuA B. melitensis vaccine provides an attractive strategy to protect against inhalational infection with virulent B. melitensis.
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