Protective Live Oral Brucellosis Vaccines Stimulate Th1 and Th17 Cell Responses
ABSTRACTZoonotic transmission of brucellosis often results from exposure toBrucella-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 theznuAgene involved in zinc transport has been found to attenuateBrucella abortus. A similar mutation has been adapted forBrucella melitensisand tested to determine whether oral administration of ΔznuAB. melitensiscan confer protection against nasalB. melitensischallenge. A single oral vaccination with ΔznuAB. melitensisrapidly cleared from mice within 2 weeks and effectively protected mice upon nasal challenge with wild-typeB. melitensis16M. 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-γ−/−) mice also showed protection in both spleens and lungs, albeit protection that was not as effective as in immunocompetent mice. Although IFN-γ, 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 ΔznuAB. melitensisvaccine provides an attractive strategy to protect against inhalational infection with virulentB. melitensis.