VALIDATION STUDY OF H10407 ENTEROTOXIGENIC E COLI (ETEC) CHALLENGE STRAIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Enterotoxigenic E. coli (ETEC) are bacteria that commonly cause severe diarrhea among children in developing countries. ETEC also cause diarrhea in travelers and military personnel in developing countries. Investigators in the Center for Immunization Research at Johns Hopkins are collaborating with investigators from the Navy to develop an antibody preparation that may protect against ETEC. The preparation is derived from the milk of cows vaccinated with proteins from the surface of ETEC. To test the cows' milk preparation, volunteers will be admitted to a research facility and drink an antibody preparation or a placebo three times per day, after meals, for 7 days. On the third day they will ingest a dose of ETEC that is sufficient to cause diarrhea in at least 60% of unprotected subjects. If the antibody preparation protects against the ETEC challenge, fewer subjects ingesting the antibody preparation will get sick than those ingesting placebo. Before carrying out the challenge study, a small trial was conducted to test the ETEC strain that will be used for the challenge. Five healthy subjects aged 18 to 45 were admitted to the GCRC. The next day they ate a light breakfast, fasted for 90 minutes, and ingested ETEC strain H10407 at a dose of 10(9) CFU, and then fasted for 90 more minutes. After this challenge they were monitored closely, and all stools were collected, graded, and weighed to determine how many subjects On Day 5, or sooner if indicated, they began antibiotics to eradicate the challenge strain. They were discharged by Day 7. As noted above, this challenge model will be used to test a bovine antibody preparation. In addition, the same challenge strain will be used to evaluate potential ETEC vaccine strains.