Evaluating the Safety and Immune Response to a Live H7N9 Influenza Virus Vaccine Followed by an Inactivated H7N9 Influenza Virus Vaccine, Given at Varying Intervals

H7N9 avian influenza (AI) viruses have been responsible for a recent outbreak of illness in
humans in China, which was associated with severe respiratory illnesses resulting in acute
respiratory distress syndrome (ARDS) and intensive care unit (ICU) admissions. The purpose
of this study is to evaluate the safety, infectivity, and immunogenicity of a live
attenuated H7N9 A/Anhui/13 cold adapted (ca) influenza virus vaccine followed by a boost
with an inactivated subvirion H7N9 vaccine at varying intervals.

This study will enroll participants into five cohorts. Participants in Cohorts 1, 2, 3, and
4 will be admitted to an isolation unit on Study Day -2. On Study Day 0, participants will
receive one dose of the H7N9 A/Anhui/13 ca influenza virus vaccine via a nose spray device.
While in the isolation unit, participants will undergo a physical examination and nasal wash
each day, and a blood collection on select days. Participants will remain in the isolation
unit for at least 9 days after receiving the vaccine, but possibly longer, depending on
their test results.

Participants in Cohorts 1 and 2 will return to the isolation unit 4 to 8 weeks after
receiving the first vaccine (at approximately Day 28). They will receive the second dose of
the H7N9 A/Anhui/13 ca influenza virus vaccine and repeat all of the same procedures that
occurred after the first vaccination.

Participants will then receive one dose of the inactivated subvirion H7N9 vaccine 1 month
(Cohort 1) or 2 months (Cohort 2) after receiving the second vaccine.

Participants in Cohorts 3 and 4 will receive the inactivated subvirion H7N9 vaccine either 1
month (Cohort 4) or 2 months (Cohort 3) after receiving one dose of the live attenuated
vaccine. For Cohorts 1-4, participants study visits will occur 7, 14, 28, and 90 days after
receiving the vaccine and will include a medical history review, physical examination, and
blood collection at select visits.

Participants in Cohort 5 will receive one dose of the inactivated subvirion H7N9 vaccine at
Day 0 and one dose at Day 28. Study visits will occur on Days 0, 7, 28, 35, 42, 56, and 118,
and will include blood collections and physical examinations. Participants in Cohort 5 will
not be admitted to the isolation unit.

Inclusion Criteria:

- Adult males and non-pregnant females between 18 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.

- General good health, without significant medical illness, physical examination
findings, or significant laboratory abnormalities as determined by the investigator

- Agree to storage of blood specimens for future research

- Available for the duration of the trial

- Willingness to participate in the study as evidenced by signing the informed consent
document

- Female participants 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 participants will be
considered being of childbearing potential except those who have undergone
hysterectomy and those in whom menopause occurred at least 1 year prior to the study.

Exclusion Criteria:

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

- Currently breastfeeding

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, or renal disease by history, physical examination, and/or
laboratory studies including urine testing

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

- Previous enrollment in an H7 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 participant in the trial or would render the participant unable to
comply with the protocol

- History of anaphylaxis

- Allergy to oseltamivir as determined by participant 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 test (e.g.,
Western blot or HIV-1/HIV-2 differentiation assay) 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

- History of asplenia

- Body mass index (BMI) greater than 40

- 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 study. More
information on this criterion is available in the protocol.

- 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

- History of hypersensitivity to any component of the investigational product including
egg or egg protein, or serious, life threatening, or severe reactions to previous
influenza vaccinations

- Individuals who use intranasal medications chronically

- Receipt of antiviral therapy or antiviral agents within 48 hours prior to receipt of
investigational product