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AssigneeUniversity of Florida Research Foundation, Inc.
InventorRoy Curtiss, III
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Bacterial pathogens have evolved means to succeed as pathogens by infecting without recognition by receptors triggering innate immunity, by suppressing induction of immunity and by inducing immune responses to antigens that confer no protectives immunity. Embodiments described herein circumvent these abilities in Salmonella so as to provide a vector system that induces maximal protective immune responses. Another major problem in using live attenuated bacterial vaccine vectors is the accumulation of attenuating mutations that confer a virulence and safety but which decrease the ability of the vaccine to invade cells in the MALT to colonize and persist in internal effector lymphoid tissues. The embodiments disclosed herein solve this problem in multiple ways by using regulated delayed in vivo shut off of virulence genes, regulated delayed synthesis of recombinant protective antigens and regulated delayed lysis in vivo to confer biological containment with no persistence of vaccine cells and no survival if excreted.
An attenuated microorganism that comprises an expression construct engineered to synthesize two or more Brucella proteins, the expression construct comprising two or more polynucleotide sequences each encoding at least one of the two or more Brucella proteins, wherein upon administration to an animal host, the microorganism expresses and delivers the two or more Brucella proteins to the animal host,
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