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Arthritis and Immunology Research Program

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OMRF anthrax discovery could lead to improved vaccine

Hiding in Plain Sight: OMRF researchers discover rogue immune cells in healthy adults

A. Darise Farris, Ph.D. Associate Member, Arthritis and Immunology Research Program Adjunct Associate Professor, Departments of Microbiology & Immunology and   Pathology, University of Oklahoma Health Sciences Center

Patients with certain autoimmune diseases like lupus and Sjögren's syndrome make abnormal immune responses to healthy tissue, in particular to components of the cell nucleus, where genetic information is stored.  Most of these lupus "autoantigens" are also either DNA- or RNA-binding proteins.  Studies in my laboratory have focused primarily on learning how the immune system normally learns not to respond to these types of nuclear components and, conversely, why these mechanisms don't work in lupus.  Our major approach has been to create and study genetically engineered mice that have very large numbers of immune T or B cells that can specifically bind to one particular RNA-binding lupus autoantigen called "La" that was discovered by our own Dr. Morris Reichlin.  Because a normal mouse or person has as few as one in a million such cells —too few to study—, these special mice, along with mice that have been engineered to express the human La antigen, are allowing us to find out for the first time how the immune system normally deals with these particular types of autoreactive immune cells.  In the near future, we will have the capacity to study these questions in mice that have autoimmune pre-disposing genes in their genetic backgrounds that will allow us to find out exactly why and how certain genes promote autoimmunity.

More recently, our lab has partnered with Dr. Judith James to develop novel approaches to anthrax vaccination.  Dr. James and her team are currently identifying short region (peptides) of the anthrax toxin proteins that are specifically bound by antibodies.  The development of antibodies that can neutralize, or inhibit, the activity of anthrax toxins is the goal of vaccination; unfortunately, not all antibodies have this property.  Our group will use the information obtained by Dr. James to determine which of the toxin component peptides can induce neutralizing antibodies.  We will then create novel vaccine candidates by coupling the desirable peptides to a recombinant form of protective antigen, which will be initially tested in mice.  It is our hope that these studies will lead to a safer and move effective anthrax vaccine.