Celiac disease is a common and debilitating gastrointestinal disorder. It is caused by an inappropriate immunological response to gluten. Although celiac disease can usually be controlled by strict avoidance of gluten in the diet, the ubiquity of gluten in the modern diet makes such a strategy difficult and there is a need for new therapies for celiac disease. This application tests the feasibility of using oral antibody therapy as an adjunctive therapy for celiac disease. Antibodies specific for gluten components may be able to block the immune response to gluten-derived peptides. Avaxia is developing AVX-176, a polyclonal anti-gluten antibody, that is designed to be ingested with meals to inhibit the response to low levels of gluten. AVX-176 is isolated from the colostrum (early milk) of cows that have been immunized with a component of gluten. Bovine colostral antibodies are stable to gastric digestion, safe for oral administration, and inexpensive to manufacture on a large scale. We have already produced the antibody to be used in this study. In this Phase I SBIR, the antibody will be tested for its ability to bind the proteins associated with toxicity in celiac disease: gliadin, glutenin, gluten-derived peptides, and related storage proteins from other grains. The ability of the antibody to inhibit activation of the innate immune system and enzyme-mediated peptide deamidation will also be assessed. These studies will establish the feasibility of using an orally delivered anti-gluten antibody for celiac disease. In the Phase II SBIR, the efficacy of the anti-gluten antibodies will be tested in in vivo models of celiac disease. In addition, the development and manufacture of GMP material suitable for a Phase I clinical trial will be initiated. It is hoped that these studies will lead to the rapid development of a new therapeutic agent for celiac disease. PUBLIC HEALTH RELEVANCE: Celiac disease is a common and debilitating gastrointestinal disorder that is caused by an inappropriate immune response to wheat gluten. This application is aimed at developing an oral antibody product that will bind to gluten and block its toxicity in the intestinal tract.