Author
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Nystrom, Evelyn |
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GANSHEROFF, L - UNIF SRVCS UNIV HLTH SCI |
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MILLS, M - UNIF SRVCS UNIV HLTH SCI |
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TWIDDY, E - UNIF SRVCS UNIV HLTH SCI |
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MOON, H - IOWA STATE UNIVERSITY |
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O'BRIEN, A - UNIF SRVCS UNIV HLTH SCI |
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 2/13/2002 Publication Date: 5/20/2002 Citation: N/A Interpretive Summary: Cattle are important reservoirs of Shiga-like toxin-producing Escherichia coli O157:H7 and other enterohemorrhagic E. coli (EHEC), foodborne pathogens that cause severe diarrhea and sometimes kidney failure and death in humans. Our goal is to develop an effective vaccine to prevent cattle from becoming infected and transmitting EHEC O157:H7 to humans. EHEC O157:H7 require intimin, encoded by the eae gene locus, to colonize and cause intestinal damage in intestinal damage in calves. Similarly, intimin is also necessary for intestinal lesion formation in newborn piglets. We believe that an immune response to intiminO157 may be effective in reducing the amount of O157:H7 in cattle and are using neonatal pigs to determine if antibodies against intiminO157 can interfere with EHEC O157:H7 infections. We vaccinated pregnant pigs against intiminO157 and showed that these pigs developed antibodies against intiminO157 in their serum and colostrum. At 2 to 10 days after they were experimentally challenged with Shiga toxin-negative E. coli O157:H7 strain 87-23, piglets that ingested colostrum from intiminO157- vaccinated dams had fewer of the inoculated bacteria in their intestines than did piglets that nursed sham-vaccinated dams. The intestinal surfaces of piglets that nursed intiminO157-vaccinated dams, but not those that nursed the sham-vaccinated dams, were protected from E. coli O157:H7-induced lesions. These results demonstrate that antibodies against intiminO157 can interfere with EHEC O157:H7 infections and show that intiminO157 is a viable candidate for an EHEC O157:H7 anti-transmission vaccine. Technical Abstract: Cattle are important reservoirs of enterohemorrhagic Escherichia coli (EHEC) O157:H7 that cause disease in humans. Both dairy and beef cattle are asymptomatically and sporadically infected with EHEC. Our long-term goal is to develop an effective vaccine to prevent cattle from becoming infected and transmitting EHEC O157:H7 to humans. We used passive immunization of neonatal piglets (as a surrogate model) to determine if antibodies against EHEC O157 adhesin (intiminO157) inhibit EHEC colonization. Pregnant swine (dams) with serum anti- intimin titers = 100 were vaccinated twice with purified intiminO157 or sham-vaccinated with sterile buffer. IntiminO157- specific antibody titers in colostrum and serum of dams were increased after parenteral vaccination with intiminO157. Neonatal piglets were allowed to suckle vaccinated or sham-vaccinated dams for up to 8 h before they were inoculated with 10**6 CFU of a Shiga toxin-negative (for humane reasons) strain of EHEC O157:H7. Piglets were necropsied at 2 to 10 d after inoculation, and intestinal samples were collected for bacteriological counts and histopathology. Piglets that ingested colostrum containing intiminO157-specific antibodies from vaccinated dams, but not those nursing sham- vaccinated dams, were protected from EHEC O157:H7 colonization and intestinal damage. These results establish intiminO157 as a viable candidate for an EHEC O157:H7 anti-transmission vaccine. |