Safety and Effectiveness of a Seasonal Live Attenuated Influenza Vaccine in a Human Challenge Model of Infection With Wild-type (wt) Influenza A/California/2009 (H1N1)-Like Virus

This study will evaluate the immune response produced by a seasonal LAIV. The initial
vaccination will be followed 2 months later by an open-label inpatient trial evaluating the
subsequent response (safety, infectivity, clinical response, and viral shedding) following
administration of the wild-type A/California/2009-like influenza challenge virus.

Healthy adult participants will be randomized into two groups. On Day 0, Group 1 will receive
a single dose of an intranasal LAIV. Group 2 will receive a single dose of intranasal
placebo. Study visits will occur on Days 0, 3, 7, 14, and 28.

On Day 54, participants will be admitted to the isolation unit for the inpatient portion of
the study, and both groups will receive an intranasal dose of wild-type
A/California/2009-like influenza challenge virus on Day 56. On Day 65, participants who are
no longer shedding virus will be discharged.

Follow-up study visits will occur after discharge from the isolation unit on Days 70, 84,
112, and 180. Study visits during either the inpatient or outpatient portions of the trial
may include physical examinations, collection of blood and urine samples, electrocardiogram
(ECG), nasal washes and swabs, and nasal mucus weighing.

Inclusion Criteria:

- Adult males and non-pregnant females between 18 years and 45 years of age. Children
will not be recruited or enrolled in this study 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.

- Likely to be susceptible to the challenge virus as determined by a baseline serum HAI
antibody titer to the A/California/09 wild-type virus of 1:8 or less.

- 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 subjects 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 child-bearing
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 breast-feeding.

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, endocrinologic or renal disease by history, physical
examination, and/or laboratory studies including urine testing. Levels of alanine
aminotransferase (ALT), aspartate transaminase (AST), bilirubin greater than 2 times
the upper limit of normal (ULN) or otherwise clinically significant as determined by
the Principal Investigator (PI), will be exclusionary at baseline, prior to
vaccination. Complete blood count (CBC) with differential outside of the normal
reference range and deemed clinically significant by the PI.

- Body Mass Index (BMI) of less than 18.5 or greater than 40.

- 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.

- 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.

- History of anaphylaxis.

- 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.

- 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.

- Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is
greater) or any unlicensed vaccine within 6 months of enrollment.

- History of a surgical splenectomy.

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

- Current smoker unwilling to stop smoking for the In-patient Challenge Phase of the
study.

- A current smoker includes anyone stating they currently smoke any amount of a
tobacco product.

- The decision to exclude a potential subject is determined by medical history and
a clinician's clinical judgment based on the physical examination.

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

- Allergy to eggs or egg products.

- Household contacts of individuals at higher risk for influenza-related complications,
including: Persons greater than or equal to 65 years of age or less than 5 years of
age; or persons with chronic pulmonary disease (e.g., asthma, emphysema), chronic
cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, ischemic heart
disease), metabolic disease (e.g., diabetes mellitus, renal dysfunction,
hemoglobinopathies), immunosuppression, neurological and neurodevelopmental
conditions, children and teenagers who are receiving long-term aspirin therapy, or
women who are pregnant or who are trying to become pregnant.

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

- Positive ELISA and confirmatory tests for human immunodeficiency virus-1 (HIV-1),
hepatitis C virus (HCV), or hepatitis B (Positive hepatitis B virus surface antigen).

- Clinically significant abnormalities on ECG.

- Clinically significant abnormality as deemed by the PI on echocardiographic testing.

- Known close contact with anyone known to have influenza or influenza-like illness in
the past 7 days.