Efficacy of Anti-CFA/I and CfaE Bovine Milk Immunoglobulin Against Challenge With H10407 ETEC Expressing CFA/I
Efficacy of Anti-CFA/I and CfaE Bovine Milk Immunoglobulin Against Challenge With H10407 ETEC Expressing CFA/I
The purpose of this study is to assess anti-CFA/I and anti-CfaE BIgG safety and to determine
 protective efficacy of anti-CFA/I and anti-CfaE BIgG against diarrhea after challenge with
 H10407, a CFA/I-expressing ETEC strain.
This is a Randomized, double-blinded, placebo-controlled trial involving up to 33 subjects.
 Subjects will be randomized into one of the following three groups.

 Group N Product

 1. 10 BIgG anti-CFA/I

 2. 10 BIgG anti-CfaE

 3. 10 LactoFree® Lipil®

 Volunteers will receive the test article three times daily following meals beginning 2 days
 prior to oral ETEC challenge (strain H10407). Test article will be administered for a total
 of 7 days. Monitoring procedures will assess volunteer safety, the primary endpoint
 (diarrhea), stool microbiology (H10407 excretion), and ETEC-specific immunology. All
 volunteers will receive antibiotic treatment (ciprofloxacin, trimethoprim-sulfamethoxazole or
 amoxicillin) starting 5 days after ETEC challenge or sooner based on pre-defined clinical
 criteria. Follow-up visits for 2 weeks post-discharge will monitor safety and immunological
 parameters.
Inclusion Criteria:

 -  Male or female between 18 and 45 years of age.

 -  General good health, without significant medical illness, abnormal physical
 examination findings or clinical laboratory abnormalities as determined by principal
 investigator.

 -  Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by
 passing a written examination (pass grade ≥ 70%)

 -  Willing to participate after informed consent obtained.

 -  Available for all planned follow-up visits.

 -  Negative serum pregnancy test at screening and a negative urine pregnancy test on the
 day of admittance to the inpatient phase 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).

 Exclusion Criteria:

 -  Presence of a significant medical condition, (e.g. psychiatric conditions or
 gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active
 gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or
 illicit drug abuse/dependency), or other laboratory abnormalities which in the opinion
 of the investigator precludes participation in the study.

 -  Immunosuppressive illness or IgA deficiency (below the normal limits)

 -  Positive serology results for HIV, HBsAg, or HCV antibodies.

 -  Significant abnormalities in screening lab hematology, serum chemistry, urinalysis or
 EKG (EKG in volunteers ≥ 40 years), as determined by PI.

 -  Allergy to fluoroquinolones, trimethoprim-sulfamethoxazole, or ampicillin/penicillin
 (excluded if allergic to two of three).

 -  Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on
 a regular basis.

 -  History of diarrhea in the 2 weeks prior to planned inpatient phase

 -  Regular use of laxatives, antacids, or other agents to lower stomach acidity (regular
 defined as at least weekly).

 -  Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2
 blockers, or antacids within 48 hours of dosing.

 -  Travel to countries where ETEC or cholera infection is endemic (most of the developing
 world) within two years prior to dosing.

 -  History of vaccination for or ingestion of ETEC, cholera, or LT toxin.

 -  Stool culture (collected no more than 1 week prior to admission) positive for CFA/I +
 ETEC or other bacterial enteric pathogens (Salmonella, Shigella and Campylobacter).

 -  Use of any investigational drug or any investigational vaccine within 30 days
 preceding the first dose of test article, or planned use during the active study
 period.

 -  Clinical history of lactose intolerance or allergy to milk or milk products.

 -  Use of any medication known to affect the immune function (e.g., corticosteroids and
 others) within 30 days preceding the first dose of study vaccine, or planned use
 during the active study period.

 -  Inability to tolerate an over-the-counter, lactose-free, infant, powder formula
 suspended in 150 mL sodium bicarbonate buffer (based on requirement for frequent
 dosing).