The ultimate goal of the research proposed is the development of vaccines against intracellular pathogens. The model system to be employed is the Brucella spp, a causative agent of infectious abortion in animals (Bang's disease) and undulant fever, a chronic debilitating disease in humans. Historically, elimination of brucellosis as a public health threat has relied on the elimination of animal infection. However, the potential threat of bioterrorism or biowarfare use of this class B select agent underscores the need to develop direct intervention strategies to preserve public health. The long range goal is to develop an enabling technology for the enhancement and delivery of promising vaccines through controlled release. The objectives of this application are to entrap live, highly attenuated vaccine strains, in specialized coatings designed for controlled release, and test their efficacy in a mouse model. We propose that the use of controlled release vehicles can potentiate the use of safe but moderately protective strains and produce efficacious, marketable vaccines. We have several lines of strong preliminary data to support this work. These include i) Brucella attenuated strains developed through specific mutagenesis and characterized with regard to safety and efficacy in a mouse model and, ii) vaccination data documenting the performance of novel proteins as a robust erodible biopolymer in vaccine delivery systems. We will test our hypothesis with the following specific aims: 1) Entrap target strains in capsule formulations enabling sustained release and 2) Test the safety and efficacy of these novel encapsulated strains in a mouse model.
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