A Phase 2 Influenza A Challenge Study Following Oral Administration of an H1N1 HA Ad-Vector Seasonal Flu Vaccine

This is a Phase 2 randomized, placebo- and active-controlled, two-part study in which healthy
adult volunteers with low or undetectable pre-existing antibodies against
A/California/7/2009(H1N1) pdm09-like virus will be challenged with an influenza A/H1N1 human
challenge strain approximately 90 days after vaccination with a single dose of H1N1 HA
Adenoviral-vector based seasonal influenza vaccine and dsRNA adjuvant (VXA-A1.1), an
injectable QIV vaccine, and/or placebo.

An independent SMC will oversee the safety of the study.

To accommodate the limited size of the isolation unit that will be utilized for the challenge
and post-challenge sequestration period, subjects will move through the study (enrollment,
vaccination and challenge) sequentially in a total of 6 cohorts. Each cohort will randomize
30 subjects to obtain approximately 25 subjects per cohort for the challenge phase. Subjects
will be randomized in a ratio of 2:2:1 (VXA-A1.1: QIV: Placebo).

The study will be conducted in two parts.

Part A: Subjects will be randomized in a double-blinded manner to receive a single
administration of one of three treatment arms:

- Arm 1: VXA-A1.1 oral vaccine + placebo IM

- Arm 2: QIV IM injection + oral placebo

- Arm 3: Placebo IM injection + oral placebo

Subjects will return to the site for ~8 visits and be contacted remotely at defined time
points to be followed for immunogenicity and safety during study Part A.

Part B: Subjects will be challenged with a wild-type influenza A H1 virus strain ~90 days
following vaccination. Blood samples will be collected to evaluate immunogenicity. Subjects
will remain in the isolation unit for 6 to 9 days post-challenge.

Following challenge, influenza symptoms and signs will be assessed during the sequestration
period. Blood samples and nasopharyngeal swab samples will be collected. Vital signs will be
measured every 4 hours during waking hours.

After release from the isolation unit subjects will return to the site 30 days
post-challenge. Part B will continue for purposes of collecting long term safety follow-up
(SAEs and AESIs/NOCIs) via phone contacts through 1 year post-vaccination (Day 365).

Inclusion Criteria:

1. Male or female volunteers aged 18 - 49 years, inclusive

2. Able to give written informed consent

3. Low pre-existing antibodies to the study vaccine

4. In general good health (no clinically significant health concerns)

5. Safety laboratory normal range or NCS (with few exceptions)

6. Body mass index between 17 and 35

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

8. Female participants must have a negative pregnancy test at screening

Exclusion Criteria:

1. Receipt of any influenza vaccine within two years prior to study

2. Use of any investigational vaccine/adjuvanted vaccine within 8 weeks of study

3. Use of any investigational drug or device within 4 weeks of study

4. Use of any licensed vaccine within 30 days of study

5. Presence of significant uncontrolled medical or psychiatric illness within 3 months of
study

6. Clinically significant and/or protocol defined ECG abnormality

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

8. Cancer, or treatment for cancer, within 3 years of study

9. History of drug, alcohol or chemical abuse within 1 year

10. Receipt of blood or blood products within 6 months of study

11. Donation of blood within 4 weeks of study

12. Presence of a fever ≥ 38ºC measured orally at baseline

13. Stool sample with occult blood at screening

14. Positive urine drug screen for drugs of abuse at screening

15. Positive breath or urine alcohol test at screening or baseline

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

17. History of serious reactions to any vaccination such as anaphylaxis, respiratory
problems, Guillain-Barre syndrome, hives or abdominal pain

18. Asthma, bronchiectasis or chronic obstructive pulmonary disease

19. Any known allergy or intolerance to oseltamivir