Intimin: Candidate for an Escherichia coli 0157:H7 Anti Transmission Vaccine (9702074)

Enterohemorrhagic Escherichia coli (EHEC) 0157:H7 is the most common infectious cause of bloody diarrhea in the U.S., and an occasional consequence of this infection, the hemolytic uremic syndrome,is the primary cause of acute kidney failure in U.S. children. Most U.S. cases of EHEC 0157:H7 disease have occurred after ingestion of under cooked, contaminated hamburger. Cattle are reported to be asymptomatically and sporadically infected with this organism. EHEC have been shown to adhere to the intestinal epithelium of neonatal calves via a bacterial surface protein called intimin. The long-term goal of our project is to develop an inexpensive vaccine to prevent cattle from becoming infected with EHEC and, thus, prevent transmission from cattle to humans. To achieve this objective, we will: i) evaluate whether intimin is required for EHEC 0157:H7 colonization of older calves; ii) assess whether oral administration of anti-intimin antibodies interferes with intestinal colonization and lesion formation caused by EHEC 0157:H7 in piglets, a surrogate for calves;iii) test whether pregnant pigs administered intimin by a non-oral route elicit anti-intimin antibody responses in serum, colostrum, and milk and whether suckling piglets born of these immunized sows are protected from infection with E. coli 0157:H7; iv) compare the antibody responses of mice to intimin and a set of intimin fragments administered by different routes and identify the smallest fragment that elicits antibodies capable of blocking EHEC adherence to epithelial cells; and v) develop a plant that expresses intimin or a fragment thereof as a potential edible vaccine for cattle.