The goal of our proposed research is to develop a Brucella vaccine that is safe for human use. Our approach has explored the use of live attenuated vaccines, since subunit vaccines have shown little real promise. Our approach combines the optimal features of a deliverable vaccine that is safe, free of side effects and efficacious in humans with enhanced immune stimulation through microencapsulation. The competitive advantages and innovations of our approach are: (1) use of a highly attenuated, safe, gene knockout, live B. melitensis mutants;(2) manufacturing with unique disposable closed system technologies, and (3) oral/intranasal delivery in a novel microencapsulation-mediated controlled release formula to optimally provide the long term mucosal immunostimulation required for protective immunity. Based upon our preliminary data, we postulate that our vaccine delivery system will ultimately be storage stable, administered orally or intranasally, and generally applicable to a number of select agents. We present a welldesigned 5-year timeline with milestones for developing GMP-produced vaccine for vaccination-aerosol challenge studies in non-human primates as a pathway to a clinical Investigational New Drug studies on the path to FDA Biological License Application. The development of the proposed product takes full advantage of a strong team and ongoing research with bacterial genetics and testing in multiple animal models coupled with novel manufacturing and microencapsulation technologies that balance product safety, stability, costs, and potency.
No human brucellosis vaccine is available despite the continued presence of the organism in 86 countries in which tens of thousands of humans are treated for brucellosis annually. Although the ongoing threat to the US has been greatly reduced, the potential threat to the United States remains high and retains both public health and economic impact.
|Pandey, Aseem; Lin, Furong; Cabello, Ana L et al. (2018) Activation of Host IRE1?-Dependent Signaling Axis Contributes the Intracellular Parasitism of Brucella melitensis. Front Cell Infect Microbiol 8:103|
|Russell-Lodrigue, Kasi E; Killeen, Stephanie Z; Ficht, Thomas A et al. (2018) Mucosal bacterial dissemination in a rhesus macaque model of experimental brucellosis. J Med Primatol 47:75-77|
|Matz, L M; Kamdar, K Y; Holder, M E et al. (2018) Challenges of Francisella classification exemplified by an atypical clinical isolate. Diagn Microbiol Infect Dis 90:241-247|
|Langsjoen, Rose M; Haller, Sherry L; Roy, Chad J et al. (2018) Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models. MBio 9:|
|Raja, B; Goux, H J; Marapadaga, A et al. (2017) Development of a panel of recombinase polymerase amplification assays for detection of common bacterial urinary tract infection pathogens. J Appl Microbiol 123:544-555|
|Nunes, Marcio R T; Contreras-Gutierrez, María Angélica; Guzman, Hilda et al. (2017) Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus. Virology 504:152-167|
|Rossetti, Carlos A; Drake, Kenneth L; Lawhon, Sara D et al. (2017) Systems Biology Analysis of Temporal In vivo Brucella melitensis and Bovine Transcriptomes Predicts host:Pathogen Protein-Protein Interactions. Front Microbiol 8:1275|
|Paterson, Andrew S; Raja, Balakrishnan; Mandadi, Vinay et al. (2017) A low-cost smartphone-based platform for highly sensitive point-of-care testing with persistent luminescent phosphors. Lab Chip 17:1051-1059|
|Park, Arnold; Yun, Tatyana; Vigant, Frederic et al. (2016) Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway. PLoS Pathog 12:e1005659|
|Pandey, Aseem; Cabello, Ana; Akoolo, Lavoisier et al. (2016) The Case for Live Attenuated Vaccines against the Neglected Zoonotic Diseases Brucellosis and Bovine Tuberculosis. PLoS Negl Trop Dis 10:e0004572|
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