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                    BIOINFORMATICS COLLOQUIUM
               School of Computational Sciences
                    George Mason University
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        Development & Refinement of a Vaccine to Protect Against
                    Brucella and Other Diseases

                       Dr. Stephen M. Boyle
          Department of Biomedical Sciences & Pathobiology     
       Virginia-Maryland, Regional College of Veterinary Medicine


                      Tuesday, May 2, 2006
                             4:30 pm
           Verizon Auditorium, Prince William Campus
ABSTRACT 
Brucellosis is the disease caused by the Brucella spp. of bacteria 
classified as a “class B” bioterrorism agent.  The bacterium causes 
undulant fever in humans and abortions in a variety of land and marine 
mammals.  The pathogen normally replicates inside macrophages of the 
infected species.  The USDA approved Brucella abortus strain RB51 is 
used as a vaccine against bovine brucellosis in the USA, Chile, Mexico, 
Venezuela and also being introduced in India, Iraq and Iran.  Brucella 
abortus RB51 is a genetically stable, rough, attenuated naturally 
occurring mutant that is widely used as a modified live vaccine against 
bovine brucellosis as part of the cooperative State-Federal Brucellosis 
Eradication Program in U.S.A.  Strain RB51 was conditionally licensed 
as a cattle vaccine by USDA in 1996 and was granted a full license in 
March 2003.  It lacks the ability to synthesize and transport 
polysaccharide O-side chain to the cell surface.  The goals of our 
research efforts have been the refinement of strain RB51 as a better 
brucellosis vaccine and as a vector for the expression and delivery of 
protective antigens for other intracellular pathogens for which the 
induction of a strong Th1 type of immune response is needed for 
effective protection.  By homologous over-expression of Brucella 
protective antigens Cu/Zn SOD and/or O-polysaccharide, the vaccine 
efficacy of strain RB51 has been enhanced.  This has allowed us to 
develop tools for the effective expression of not only homologous but 
also heterologous antigens using strain RB51 as a vector. We have been 
able to generate RB51 based vaccines with the ability to protect 
against several intracellular pathogens at the same time. With the 
availability of entire chromosomal sequence of prokaryotes and 
eukaryotes and our ability to design specific primers for cloning, and 
expression of heterologous antigens in Brucella, the task of generating 
multivalent vaccines has become routine.  Strain RB51 expressing 
protective antigens from Mycobacterium tuberculosis, M. bovis, Neospora 
caninum, Bacillus anthracis, Yersinia pestis and Francisella tularensis 
have been generated.  Several of these candidate vaccines are under 
investigation for their ability to induce antigen specific protective 
immune response against a challenge in animal models and some show 
significant promise.     


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Refreshments are served at 4:00 pm. Find the schedule and directions at
http://www.binf.gmu.edu/colloq.html