Evaluating the Safety and Immunogenicity of a Live Attenuated Virus Vaccine to Prevent Influenza H3N2v Disease

The potential for widespread human disease due to the H3N2v influenza viruses is
considerable. Infection with these viruses would most likely impact young children. This
study will evaluate the safety and immunogenicity of the H3N2v MN 2010/AA ca live attenuated
influenza vaccine (H3N2v LAIV) in healthy children and adults, 6 to 26 years old.

The study will enroll participants sequentially in four groups: Group 1 will include H3N2v
seronegative adults ages 18-26 years; Group 2 will include H3N2v seropositive adolescents
ages 13-17 years; Group 3 will include H3N2v seronegative adolescents ages 13-17 years; and
Group 4 will include children ages 6 to 12 years, who will not be screened for H3N2v
serostatus.

At study entry (Day 0), participants in Group 1 will receive one dose of H3N2v LAIV.
Participants in Groups 2, 3, and 4 will be randomly assigned to receive two doses of either
H3N2v LAIV or placebo, receiving the first dose on Day 0 and the second dose on Day 28. On
Day 84, all participants will receive one dose of H3N2v IIV (an inactivated booster vaccine).

Participants will attend several additional study visits through Day 180. These visits may
include a physical examination; respiratory examination; and collection of blood, urine, or
nasal fluids.

Inclusion Criteria:

- Males and non-pregnant females between 6 and 26 years of age inclusive.

- For children, presence of an adult caregiver who is in good health and able to
understand and carry out the requirements

- 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. Verbal assent will be obtained from minors 6 to 12 years of age and signed
assent will be obtained from minors 13 and older.

- Female subjects of childbearing potential must agree to use effective birth control
methods for the duration of the study (e.g., pharmacologic contraceptives including
oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with
spermicide; intrauterine device; abstinence from heterosexual intercourse, surgical
sterilization).

Exclusion Criteria:

- Anticipated direct routine [e.g. weekly or more frequent] contact with individuals
younger than the designated age groups being studied as a result of household contact,
occupation, or participation in day care with such individuals.

- Pregnancy as determined by a positive urine or serum human choriogonadotropin (β-HCG)
test.

- Currently breast-feeding.

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, or renal disease by history or physical examination.

- 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.

- 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).

- Use of aspirin or salicylate-containing medications within 28 days prior to
randomization or expected receipt through 28 days after final vaccination.

- History of Guillain-Barré Syndrome.

- Known history of HIV, hepatitis C, or active hepatitis B infection.

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

- 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.

- Allergy to eggs or egg products, gentamicin, or gelatin.

- Chronic use of intranasal medications.