Expression of Brucella Antigens in Vaccinia Virus to Prevent Brucellosis in Humans: Protection Studies in Mice

Abstract

Abstract : The current work has the overall objectives of genetically engineering mono and poly-valent, IL-12 producing vaccinia/Brucella recombinant vaccines using synthetic E/L promoters and to test such vaccinia recombinants for their ability to induce a protective immune response against challenge with virulent Brucella in a mouse model. For an effective and strongly protective immune response it may he necessary to combine vaccination with vaccinia/Brucella recombinants with the inoculation of DNA vaccines. At this stage the following has been achieved: 1. Demonstrated Brucella Cu/Zn SOD to he a protective antigen. 2. Produced first WRvaccinia/Brucella antigen recombinants simultaneously producing IL-12. 3. Produced first WRvaccinia/Brucella recombinants producing a fusion protein of two protective Brucella antigens (SOD and L7/L12). 4. Initiated protection studies with WRvaccinia/Brucella antigen recombinants producing IL-12. i Detected additional protective Brucella antigens (BMCP24, BaBSC31 and BaPAL16.5) ready for cloning into vaccinia. 6. Produced several Brucella DNA vaccines to he used in combination with WRvaccinia/Brucella antigen recombinants and 7. Initiated production of MVA vaccinia/Brucella antigen recombinants. Based on the identification of protective antigens and the role of IL- 12, we are confident that the use of vaccinia/Brucella recombinants producing IL-12 will induce protective immunity. We are now able to produce such recombinants.