Dose-Optimization Trial of VXA-G1.1-NN in Healthy Volunteers

This study will enroll approximately 60 subjects in four cohorts of 15 subjects each. The
cohorts may be enrolled and run in parallel or overlap; they do not have to run sequentially.
The dosing for each cohort will be as follows:

Cohort 1: Multiple low dose on Days 1 and 8 Cohort 2: Multiple low dose on Days 1, 3 and 5
Cohort 3: Multiple low dose on Days 1 and 29 Cohort 4: Multiple high dose on Days 1 and 29

All subjects receiving study drug will have safety and immunogenicity assessments completed
through Study Day 57 following their initial vaccination. Subjects may also be evaluated for
persistent immunogenicity at Day 180 and will be followed for safety for 12 months following
initial vaccination (Study Day 365).

Inclusion Criteria:

1. Male or female volunteers aged 19 - 49 years

2. Able to give written informed consent.

3. Healthy (no clinically significant health concerns), as determined by medical history,
physical examination, 12-lead ECG, and vital signs at screening.

4. Safety laboratory values within the following range criteria at screening or abnormal
and not clinically significant as outlined within the clinical protocol

5. Body mass index between 17 and 35 inclusively (kg/m2)

6. Comprehension of the study requirements with ability and willingness to complete all
assessments and comply with scheduled visits and contacts.

7. Female participants must have a negative pregnancy test at baseline and fulfill one of
the following criteria:

1. At least one year post-menopausal;

2. Surgically sterile;

3. Willing to use oral, implantable, transdermal or injectable contraceptives for 30
days prior to and until 60 days after vaccination;

4. A reliable form of contraception must be approved by the Investigator

Exclusion Criteria:

1. Receipt of any investigational norovirus vaccine within past 2 years

2. Administration of any investigational vaccine, drug or device within 8 weeks preceding
vaccination, or planned use of the above stated during the study through the 12-month
safety follow-up.

3. Administration of any licensed vaccine within 30 days prior to vaccination.

4. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic)
including institution of new medical/surgical treatment or dose alteration for
uncontrolled symptoms or drug toxicity within 3 months

5. Any one of the following ECG findings within 30 days prior to vaccination:

- QTcF interval duration > 460 msec (male) or > 470 msec (female),

- QRS interval greater than 120 msec,

- PR interval greater than 220 msec,

- Clinically significant ST-T wave changes or pathologic Q waves.

6. Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies.

7. Cancer, or treatment for cancer treatment, within past 3 years (excluding history of
basal cell carcinoma, squamous cell carcinoma, or cervical cancer in situ).

8. History of a hypersensitivity or allergic reaction to any component of the
investigational vaccine or placebo, including but not limited to fish gelatin.
Subjects with known fish allergies should be excluded.

9. Presence of immunosuppression or medical condition possibly associated with impaired
immune responsiveness, including diabetes mellitus.

10. Administration of any medications or treatments that may adversely affect the immune
system such as allergy injections, immune globulin, interferon, immunomodulators,
cytotoxic drugs or other drugs known to be associated with significant major organ
toxicity, or systemic corticosteroids (oral or injectable) during 3 months prior to
vaccination. Inhaled and topical corticosteroids allowed.

11. Presence of household members who have received the Ad4 or Ad7 vaccines within 2
months prior to vaccination.

12. Presence of household members who are neonates, pregnant women, or hematopoietic stem
cell transplant or solid organ transplant recipients from screening until the end of
the active period

13. History of drug, alcohol or chemical abuse within 1 year prior to vaccination.

14. Receipt of blood or blood products 6 months prior to vaccination or planned
administration during the follow-up study period.

15. Donation of blood or blood products within 4 weeks prior to vaccination or planned
donation during the study period.

16. Acute disease within 72 hours prior to vaccination defined as the presence of a
moderate or severe illness with or without fever.

during screening period).

17. Presence of fever ≥38oC

18. Stool sample with occult blood

19. Positive urine drug screen for drugs of abuse

20. Positive urine alcohol test at

21. Consistent/habitual smoking within 2 months prior to vaccination.

22. History of serious reactions to any vaccination such as anaphylaxis, respiratory
problems, hives or abdominal pain.

23. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that
could make blood draws problematic.

24. History of irritable bowel disease or other inflammatory digestive or gastrointestinal
condition that could affect the distribution / safety evaluation of an orally
administered vaccine targeting the mucosa of the small intestine.