Vaccination with a ΔnorD ΔznuA Brucella abortus mutant confers potent protection against virulent challenge

There remains a need for an improved livestock vaccine for brucellosis since conventional vaccines are only similar to 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 Delta norD Delta 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-gamma(+,) TNF-alpha(+), and poly functional IFN-gamma(+) TNF-alpha(+) 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. (C) 2016 Elsevier Ltd. All rights reserved.