Safety Study of Chimeric Vaccine to Prevent ETEC Diarrhea

The purpose of the study is to evaluate the safety and immunogenicity of dsc14cfaEsCTA2/LTB5
(Chimera) and dscCfaE administered with and without LTR192G by intradermal (ID) immunization
and to gather additional data on the administration of dsCfaE and LTR192G via transcutaneous
immunization (TCI) route. If vaccines are found to be safe and adequately immunogenic in
humans, a down-selection would occur and a phase 2b vaccination/challenge study would be
undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy
of one of these candidates by the ID or TCI route. With favorable evidence for safety,
immunogenicity, efficacy, complemented by advances in standard methodology to combine
multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be
constructed and evaluated for further clinical development.

Inclusion Criteria:

- Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of
enrollment.

- Completion and review of comprehension test (achieved > 70% accuracy).

- Signed informed consent document.

- Available for the required follow-up period and scheduled clinic visits.

- Women: Negative pregnancy test with understanding (through informed consent process)
to not become pregnant during the study or within three (3) months following study
completion.

Exclusion Criteria:

- Health problems (for example, chronic medical conditions such as psychiatric
conditions, diabetes mellitus, hypertension or any other conditions that might place
the subjects at increased risk of adverse events. Study clinicians, in consultation
with the PI, will use clinical judgment on a case-by-case basis to assess safety risks
under this criterion. The PI will consult with the Research Monitor as appropriate.

- Clinically significant abnormalities on physical examination.

- Use of immunosuppressive medications (systemic corticosteroids or chemotherapeutics
that may influence antibody development), or immunosuppressive illness, including IgA
deficiency (defined by serum IgA below the detectable limit).

- Women who are pregnant or planning to become pregnant during the study period plus 3
months beyond the last study safety visit and currently nursing women.

- Participation in research involving another investigational product (defined as
receipt of investigational product or exposure to invasive investigational device) 30
days before planned date of first vaccination or anytime through the last study safety
visit.

- Positive blood test for HBsAg, HCV, HIV-1.

- Clinically significant abnormalities on basic laboratory screening.

- Exclusionary skin history/findings that would confound assessment or prevent
appropriate local monitoring of AEs, or possibly increase the risk of an AE.

- History of chronic skin disease (clinician judgment).

- History of atopy such as active eczema.

- Acute skin infection/eruptions on the upper arms including fungal infections, severe
acne or active contact dermatitis.

- Allergies that may increase the risk of AEs.

- Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid
therapy.

- Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on
a regular basis; loose or liquid stools on other than an occasional basis.

- Prior exposure to ETEC or Vibrio cholera.

- History of microbiologically confirmed ETEC or cholera infection.

- Travel to countries where ETEC or V. cholera or other enteric infections are endemic
(most of the developing world) within two years prior to dosing clinician judgment).

- Received previous experimental ETEC or V. cholera vaccine or live ETEC or V. cholera
challenge.

- Occupation involving handling of ETEC or V. cholera currently, or in the past 3 years.