Vaccination with a ?norD ?znuA Brucella abortus mutant confers potent protection against virulent challenge
Xinghon Yang, Beata Clapp, Theresa Thornburg, Carol Hoffman, David W Pascual
There remains a need for an improved livestock vaccine for brucellosis since conventional vaccines are only ?70% efficacious, making some vaccinated animals susceptible to Brucella infections. To address this void, a vaccine capable of evoking protective immunity, while still being sufficiently attenuated to produce minimal disease, is sought. In this pursuit, the ?norD ?znuA B. abortus-lacZ (termed as znBAZ) was developed to be devoid of functional norD and znuA B. abortus genes, and to contain the lacZ as a marker gene. The results show that znBAZ is highly attenuated in mouse and human macrophages, and completely cleared from mouse spleens within eight weeks post-vaccination. Producing less splenic inflammation, znBAZ is significantly more protective than the conventional RB51 vaccine by more than four orders of magnitude. Vaccination with znBAZ elicits elevated numbers of IFN-?+, TNF-?+, and polyfunctional IFN-?+ TNF-?+ CD4+ and CD8+ T cells in contrast to RB51-vaccinated mice, which show reduced numbers of proinflammatory cytokine-producing T cells. These results demonstrate that znBAZ is a highly efficacious vaccine candidate capable of eliciting diverse T cell subsets that confer protection against parenteral challenge with virulent, wild-type B. abortus.
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