Study Confirming A Human Challenge Model and Investigating The Safety Of VLA1701

This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge
study designed to confirm a human challenge model with E. coli strain LSN03-016011/A (LT+,
ST-, CS17), as well as collect expanded safety and immunogenicity data.

The study will be carried out in two phases:

Vaccination phase: up to 34 subjects will be randomized 1:1 to receive 2 doses of either
VLA1701 or placebo orally. The doses will be given 7 days apart and subjects will be followed
as an outpatient for safety.

Challenge Phase: 30 Subjects, out of the 34 subjects, will be challenged.

After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric
illness by daily medical checks, vital sign determinations, grading and weighing of all
stools.

Inclusion Criteria:

1. Healthy male and non-pregnant female subjects aged 18 to <50 years;

2. BMI of 19.0 to 35.0 kg/m2

3. Willingness to participate after informed consent has been obtained from the subject
prior to any study related procedures.

4. Completion of a training session and demonstration of comprehension of the protocol
procedures and knowledge of ETEC-associated illness by passing a written examination.

5. If subject is of childbearing potential:

1. Negative pregnancy test at screening with understanding to not become pregnant
within 28 days after challenge;

2. Subject has practiced an effective method of contraception during the 30 days
before screening (Visit 0);

3. Subject agrees to employ adequate birth control measures for the duration of the
study.

Exclusion Criteria

1. Participated in research involving investigational product within 30 days before
planned date of first vaccination or planned use through Day 44;

2. Any prior exposure to ETEC (including LSN03-016011/A) or cholera occupationally or
received LT (Or any mutant forms of LT (e.g., LTR192G, LTR192GL211A), ETEC, or cholera
vaccine);

3. Subjects with known abnormal stooling patterns (fewer than 3 per week or more than 3
per day);

4. Known allergies to any component of the vaccine;

5. Subjects with known allergies to more than 1 planned antibiotics:

6. History of diarrhea while traveling in a developing country within the last 3 years;

7. Subjects whose occupation involves handling of ETEC or cholera bacteria;

8. Women who are pregnant or breastfeeding;

9. Significant medical conditions including chronic, immunosuppressive, malignant, or
gastrointestinal diseases (e.g. History of Irritable Bowel Syndrome (as defined by the
Rome III criteria or medical diagnosis) or gastric ulcer disease) or enteric,
pulmonary, cardiac, liver or renal disease. Some medical conditions which are
adequately treated and stable may be acceptable in the study (e.g. hypertension);

10. Significant abnormalities in screening lab hematology or serum chemistries;

11. Use of any medication known to effect the immune system (e.g. systemic
corticosteroids) within 30 days of vaccination or planned use during active study
period (excluding inhaled steroids);

12. Evidence of confirmed infection with HIV, Hepatitis B or Hepatitis C;

13. Subjects with IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay);

14. Regular use of antacids, antidiarrheal, loperamide, bismuth subsalicylate,
diphenoxylate or similar medication less than 2 weeks prior to enrolling in the study
and through the inpatient portion of the study;

15. Known or suspected alcohol abuse or illicit drug use within the last year, positive
urine toxicology for drugs of abuse;

16. Persons who are committed to an institution (by virtue of an order issued either by
the judicial or the administrative authorities);

17. Persons who are in a dependent relationship with the sponsor, an investigator or other
study team members, or the study center.

18. Any other criteria which, in the investigator's opinion, would compromise the ability
of the subject to participate in the study, the safety of the study, or the results of
the study.