Safety and Immunogenicity of Priming With Live Attenuated A/H7N9 Influenza Virus Vaccine Followed By Inactivated A/H7N9 Influenza Virus Vaccine With AS03 Adjuvant

This study will evaluate the safety and immunogenicity of one dose of H7N9 pandemic live
attenuated influenza vaccine (H7N9 pLAIV) followed by AS03-adjuvanted H7N9 pandemic
inactivated influenza vaccine (H7N9 pIIV).

This study will enroll healthy adults who will choose which study group to join. Participants
in Group 1 will receive one dose of H7N9 pLAIV in an inpatient setting at study entry (Day
0). They will remain in an isolation unit through at least Day 9. They will also receive one
dose of AS03-adjuvanted H7N9 pIIV on Day 84.

Participants in Group 2 will receive one dose of AS03-adjuvanted H7N9 pIIV at study entry
(Day 0) and a second dose of AS03-adjuvanted H7N9 pIIV at Day 84. Participants in Group 3
will receive one dose of AS03-adjuvanted H7N9 pIIV at study entry (Day 0).

All participants will attend multiple study visits through Day 264. Study visits may include
blood collection, physical examinations, and nasal wash and nasal wick procedures.

These three groups will be compared to two historical control groups who received one dose of
H7N9 pLAIV at study entry (Day 0), one dose of H7N9 pLAIV at Day 28, and one dose of
unadjuvanted H7N9 pIIV at Day 84.

Inclusion Criteria:

- Adult males and non-pregnant, non-breastfeeding females between 20 years and 49 years
of age, inclusive. Children will not be recruited or enrolled in this study because
they are not in the apparent risk group, for safety considerations, and because of the
need for isolation.

- Are in good health, as determined by medical history and targeted physical examination
to ensure any existing medical diagnoses or conditions (except those exclusionary) are
stable. More information on this criterion can be found in the protocol.

- Agree to storage of blood specimens for future research.

- Available for the duration of the trial. Subjects must be willing and able to remain
within the Isolation Unit for the specified duration of confinement.

- Provide written informed consent prior to initiation of any study procedures,
including future use of specimens.

- Female subjects of childbearing potential must agree to use effective birth control
methods for the duration of the study (for example, pharmacologic contraceptives
including oral, parenteral, and transcutaneous delivery; condoms with spermicide;
diaphragm with spermicide; intrauterine device; abstinence from heterosexual
intercourse, surgical sterilization). All female subjects will be considered being of
childbearing potential except those who have undergone hysterectomy or tubal ligation
and those in whom menopause occurred at least 1 year prior to the study.

- Agrees not to participate in another clinical trial with an investigational product
for the entire duration of the study.

- Oral temperature is less than 100.4°F.

- Pulse is 50 to 115 bpm, inclusive.

- Systolic blood pressure is 85 to 150 mm Hg, inclusive.

- Diastolic blood pressure is 55 to 95 mm Hg, inclusive.

- Female subjects of childbearing potential must have a negative urine or serum
pregnancy test within 24 hours prior to study vaccination.

Exclusion Criteria:

- Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test.

- Currently breastfeeding or planning to breastfeed at some point during the duration of
the study.

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, or renal disease by history, physical examination,
electrocardiogram (EKG) and/or laboratory studies including urine testing. Alanine
aminotransferase (ALT) levels greater than 2 times the upper normal limit will be
exclusionary at baseline, prior to vaccination.

- Any current illness requiring daily medication other than the following: vitamins,
birth control, anti-hypertensive medication, antihistamines, anti-depressant
medication, cholesterol-lowering medication, treatment for gastroesophageal reflux
disease, and thyroid medication unless approved by the PI.

- Behavioral or cognitive impairment or psychiatric disease that in the opinion of the
investigator affects the ability of the subject to understand and cooperate with the
study protocol.

- Previous enrollment in an H7 or H9 influenza vaccine trial or in any study of an avian
influenza vaccine.

- Seropositive to the H7N9 influenza A virus (serum HAI titer greater than 1:8).

- Positive urine drug toxicology test indicating narcotic use/dependency.

- Have medical, occupational, or family problems as a result of alcohol or illicit drug
use during the past 12 months.

- Other condition that in the opinion of the investigator would jeopardize the safety or
rights of a subject participating in the trial or would render the subject unable to
comply with the protocol.

- Have a history of severe reactions following previous immunization with licensed or
unlicensed influenza virus vaccines.

- Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based
adjuvants, or other components of the study vaccine.

- Allergy to oseltamivir as determined by subject report.

- Current diagnosis of asthma or reactive airway disease (within the past 2 years).

- History of Guillain-Barré Syndrome.

- Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot tests
for human immunodeficiency virus-1 (HIV-1).

- Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for
hepatitis C virus (HCV).

- Positive hepatitis B virus surface antigen (HBsAg) by ELISA.

- Known immunodeficiency syndrome.

- Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs
within 30 days prior to vaccination.

- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to
study vaccination.

- Planned receipt of any vaccine from the first study vaccination through the follow-up
visit at approximately 180 days after the final study vaccination.

- History of asplenia.

- Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 36 months prior
to vaccination.

- Have known active neoplastic disease or a history of any hematologic malignancy.

- Receipt of blood or blood-derived products (including immunoglobulin) within 6 months
prior to study vaccination.

- Current smoker unwilling to stop smoking for the duration of the inpatient stay.

- A current smoker includes anyone stating they currently smoke or use any amount
of a tobacco product, including electronic cigarettes.

- After admission to the unit, nicotine patches will be provided to current smokers
who request them for the inpatient portion of the study.

- Travel to the Southern Hemisphere within 14 days prior to study vaccination.

- Travel on a cruise ship within 14 days prior to study vaccination.

- Receipt of another investigational vaccine or drug within 30 days prior to study
vaccination.

- Any potential Immune Mediated Disease (pIMD) listed in the protocol, or other diseases
that may have an autoimmune origin.