Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults

This is an interventional treatment trial for Diarrhea Read More

Inclusion Criteria:

1. Male and female healthy adults between 18 and 50 years of age at the time of enrollment.
2. General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
3. Negative pregnancy test at screening and before the first (V0), second (V28), and third vaccinations (V56) for female volunteers of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female volunteers unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
4. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
5. Completion of a training session and demonstrated comprehension of the protocol procedures and knowledge of ETEC associated illness by passing a written examination (70% pass score).
6. Availability for the study duration, including all planned follow-up visits.
7. Received at least 2 doses of ACE527 vaccine alone or in combination with 25 ug dmLT 4-6 months prior to challenge (Part B only)

Exclusion Criteria:

1. Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
2. Significant abnormalities in screening hematology, or serum chemistry as determined by PI or PI in consultation with the Medical Officer and sponsor.
3. Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
4. Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
5. Evidence of current excessive alcohol consumption or drug dependence.
6. Volunteers whose Body Mass Index (BMI) is less than 19.0 or greater than 34.0 (kg/m2)
7. Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
8. Intention to donate blood or blood products within one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
9. Any other criteria which, in the investigator's opinion, would compromise the ability of the volunteer to participate in the study, the safety of the study, or the results of the study
10. Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
11. Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
12. Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
13. Regular (≥ weekly) use of laxatives, antacids, or other agents to lower stomach acidity.
14. Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
15. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
16. Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
17. Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48hours prior to dosing.
18. History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed (grade 3 or greater) loose stools in 24 hours).
19. Known allergy to two of the three following antibiotics: Ciprofloxacin, amoxicillin, and/or trimethoprim/sulfamethoxazole