Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of infectious
diarrhea in children in resource limited countries, and is also a frequent cause of
traveler's diarrhea in civilian and military travelers to endemic countries. ETEC strains
express a variety of colonization factors (CF) that help them attach to the intestinal wall.
Each colonization factor has one or more surface antigens (CS). One of the major surface
antigens of ETEC is CS6 (Coli surface antigen 6).

Vaccines and treatments to prevent ETEC disease are under development. Some of these target
specific enterotoxins or colonization factors. For over 40 years, we have used ETEC human
challenge studies to understand the ETEC disease process, immune response, and more recently,
to determine whether treatments or vaccines are protective or effective in mitigating
disease. B7A is the only CS6 expressing ETEC challenge strain currently used.

A modality that has shown some success in the prevention of diarrhea is passive, oral
administration of bovine milk IgG with specific activity against viral, bacterial and
parasitic enteropathogens. Passive oral administration of Bovine Serum Immunoglobulins
(BSIgG) may protect against ETEC-mediated infectious diarrhea. The hypothesized mechanism of
protection stems from the passive administration of bovine anti-tip adhesion or fimbriae
antibodies preventing their adherence in the human small intestine (the initial step in
pathogenesis), thereby preventing downstream pathogenic processes and symptomatic illness.
This study will establish the foundation for evaluating BSIgG products against numerous ETEC
CFs.

This study will explore if anti-B7A and anti- CS6 BSIgG provides protection against oral
challenge with B7A in healthy adult volunteers. There will be two inpatient admissions of
approximately 30 subjects (up to 60 total). They will receive one of three investigational
products (IP) three times daily following meals beginning 2 days prior to challenge. Each
volunteer will be challenged with CS6 expressing ETEC B7A on Day 0. The investigational
product/placebo will be administered for a total of 7 days, or until antibiotic treatment has
been administered. The investigators hypothesize that anti-CS6 BSIgG will provide protection
against B7A mediated moderate to severe diarrhea upon challenge.

Inclusion Criteria:

- Male or female between 18 and 50 years of age, inclusive.

- General good health, without significant medical illness, abnormal physical
examination findings or clinical laboratory abnormalities as determined by principal
investigator (PI) or PI in consultation with the research monitor and sponsor.

- 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 negative serum and/or urine pregnancy
test on the day of admittance to the inpatient phase for female subjects 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 subjects unable to bear children must have this documented
(e.g., tubal ligation or hysterectomy).

Exclusion Criteria:

General health 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 Immunoglobulin A (IgA) deficiency (serum IgA < 7 mg/dL or
below the limit of detection of assay)

- Evidence of confirmed infection with HIV, HBsAg, or Hepatitis C Virus (HCV), with
confirmatory assays.

- Use of any investigational product within 30 days preceding the receipt of the
investigational products, or planned use during the active study period

- Significant abnormalities in screening lab hematology or serum chemistries, as
determined by PI or PI in consultation with the research monitor and sponsor.

- Lactation or breastfeeding.

Research-related exclusions applicable to challenge

- History of microbiologically confirmed ETEC or cholera infection in last 3 years.

- Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3
years.

- Travel to countries where ETEC or cholera infection is endemic (most of the developing
world) within 3 years prior to dosing.

- Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where
ETEC infection is endemic (most of the developing world) within 3 years prior to
dosing, OR planned travel to endemic countries during the length of the study.

- Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3
years prior to dosing.

- Any prior experimental infection with ETEC strain B7A.

Study-specific Exclusion Criteria (potential increased risk or complicating outcome
ascertainment)

- Abnormal stool pattern (fewer than 3 per week or more than 3 per day).

- 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 receipt of any investigational