Submitted to: Immunology Research Workshop
Publication Type: Abstract Only
Publication Acceptance Date: 12/2/2003
Publication Date: 12/2/2003
Citation: NYSTROM, E.A. DEVELOPMENT OF AN ORAL VACCINE FOR ESCHERICHIA COLI O157:H7. ARS IMMUNOLOGY RESEARCH WORKSHOP. 2003. ABSTRACT P. 23.
Technical Abstract: Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a subset of Shiga toxin-producing E. coli (STEC), are the most common infectious cause of bloody diarrhea in the United States. A sequela of this infection, the hemolytic uremic syndrome (HUS), is the primary cause of acute kidney failure in U.S. children. Cattle are major sources of EHEC O157:H7 and other STEC pathogens associated with human infections. Our long-term goal is to identify ways to reduce EHEC infections in cattle, and thus reduce the risk of EHEC disease in humans. One approach, which is the objective of an ongoing collaboration with Alison O'Brien (USUHS, Bethesda, MD), is to develop an inexpensive, effective vaccine that will prevent cattle from becoming infected with EHEC. Intimin is an outer membrane protein of EHEC O157:H7 that is required for colonization of neonatal calves. We hypothesized that an intimin-based vaccination strategy in calves might reduce colonization of cattle with EHEC O157:H7. The demonstration that antibodies against intimin interfere with colonization and intestinal damage in neonatal pigs supports this hypothesis. We transferred the eae gene that encodes for intimin into the tobacco NT-1 cell line and demonstrated that the transformed plant cells produce intimin, that transgenic intimin is immunogenic in mice, and that feeding mice transgenic intimin reduced the length of time these animals shed EHEC O157:H7 following experimental challenge. Our collaborator, Wayne Curtis, recently scaled up the production of intimin-expressing NT-1 cells and the immunogenicity of transgenic intimin in cattle is being tested. The bacterial DNA that encodes for intimin is being modified so that it can be transferred into an edible plant that can be fed to calves and used to test the efficacy of transgenic intimin as an oral vaccine for reducing EHEC infections in cattle. Such a vaccine that reduces O157:H7 levels in cattle would help reduce EHEC infections in humans.