EVALUATION OF LIVE, ATTENUATED BRUCELLA VACCINE CANDIDATES

In light of the direct relationship between animal and human disease emphasis on the eradication of animal disease remains a viable strategy. However, residual virulence of current LAVs presents a risk to humans, as well as a potential cause of abortion in gestating hosts including wildlife reservoirs. The long-range goal of our ongoing research is the development of Brucella vaccines that avoid these pitfalls and are safe, stable, efficacious, and readily deliverable, while also free of side effects. Toward this goal we have focused on improved safety of our vaccine candidates that includes the absence of symptoms associated with infection; fever, splenomegaly, and weight loss. Based upon our preliminary data using the mouse model, we postulate that the vaccine delivery system will ultimately provide storage stable, oral or intranasal administered vaccines that will be applicable for use against a number of agents. The research proposed here provides a well-designed 5-year timeline to evaluate vaccine candidates using pregnant hosts, the primary target, to provide the strictest safety evaluation possible. The development of the proposed product takes full advantage of ongoing research of multiple investigators that have identified genes required for Brucella survival and coupled that knowledge with a novel microencapsulation technology to balance attenuation, artificial persistence and protective immunogenicity. In addition, vaccine efficacy is enhanced.The proposed work is innovative because it combines the enhanced safety (reduced pathology) of a highly attenuated mutant organism with a proprietary delivery platform providing pulsed delivery of a highly attenuated (safe), live vaccine strain that serves as a natural booster to the immune system. It is our expectation that these methods will establish a general approach for development of additional select agent vaccines. This outcome will be significant because a Brucella vaccine will be available for safe use in animals (including wild and feral species) at all stages of gestation. Furthermore, the success of this endeavor will help to stimulate support for continued experimental evaluation of safety and efficacy in nonhuman primates with the aim of direct use in humans.Based on gross and microscopic anatomical and bacteriological results using the mouse model, it is hypothesized that the vaccine candidates under investigation will stimulate a protective immune response in the absence of fever, abortion or colonization of fetal tissues in pregnant ruminants.